Abnormal uterine bleeding -...

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11/4/2014 DynaMed http://web.b.ebscohost.com.ezproxy.sibdi.ucr.ac.cr:2048/dynamed/delivery/printcitation?expand=sec-General-Information,sec-Causes,sec-History-and-Physical,… 1/13 Abnormal uterine bleeding Updated 2014 Feb 17 03:20:00 PM: ACOG Practice Bulletin 136 on management of abnormaluterinebleeding associated with ovulatory dysfunction (National Guideline Clearinghouse 2014 Feb 17) view update Show more updates Related Summaries: Heavy menstrual bleeding Endometrial ablation Polycystic ovary syndrome Hysterectomy Uterine leiomyoma Overview: terminology describing abnormaluterinebleeding varies widely initial evaluation of women presenting with abnormaluterinebleeding history should include specific details of bleeding pattern assessment for possible inherited systemic disorders of hemostasis (Kaiser Level A) testing to consider for all women with abnormaluterinebleeding pregnancy test (Kaiser Level C) complete blood count (CBC) (Kaiser Level C) additional testing guided by patient history and response to treatment endometrial sampling if increased risk of endometrial hyperplasia or neoplasia (Kaiser Level A) thyroid-stimulating hormone (TSH) if suspected anovulatory bleeding (Kaiser Level C) endocrine studies if suspected hyperprolactinemia or hyperandrogenic state factor VIII, platelets and bleeding time if suspected bleeding disorder further evaluation with ultrasound, saline infusion sonography, and/or hysteroscopy for persistent bleeding (Kaiser Level A) treatment for acute severe bleeding IV conjugated equine estrogen 25 mg (repeated at 3-4 hours if needed) may terminate endometrial bleeding in patients with dysfunctional uterinebleeding (level 2 [mid-level] evidence) oral medroxyprogesterone acetate and combination oral contraceptives appear equally effective in terminating acute uterinebleeding (level 2 [mid-level] evidence) treatment for women with irregular uterinebleeding progestogens given alone (cyclically, continuously or nearly continuously) or in combination with estrogens have limited evidence for management of anovulatory irregular bleeding (Kaiser Level B) metformin may reduce menstrual abnormalities in women with polycystic ovarian syndrome (level 2 [mid-level] evidence) consider stress reduction and weight loss (Kaiser Level C) surgical therapy for women not interested in preserving fertility (Kaiser Level C) endometrial ablation is almost as effective as hysterectomy for dysfunctional uterinebleeding (level 1 [likely reliable] evidence) for patients with abnormaluterinebleeding due to leiomyomas, surgical management determined by size, location and number of myomas (Kaiser Level C) treatment for heavy menstrual bleeding clarifying values and patient preferences may reduce hysterectomy rates for menorrhagia (level 2 [mid-level] evidence) levonorgestrel-releasing intrauterine system (LNG-IUS) appears effective for heavy menstrual bleeding (level 2 [mid-level] evidence) improves quality of life as effectively as surgery (level 1 [likely reliable] evidence) treatment of choice if hormonal treatments are acceptable and at least 12 months use anticipated (NICE A recommendation) combined oral contraceptives is second-line drug treatment option (NICE B recommendation) other medical options include nonsteroidal anti-inflammatory drugs (NSAID), tranexamic acid (Lysteda), oral or injected progestins, and danazol endometrial ablation preferable to hysterectomy in women with heavy menstrual bleeding alone and uterus ≤ 10 week

Transcript of Abnormal uterine bleeding -...

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Abnormal uterine bleeding

Updated 2014 Feb 17 032000 PM ACOG Practice Bulletin 136 on management of abnormaluterinebleeding associated with

ovulatory dysfunction (National Guideline Clearinghouse 2014 Feb 17) view update Show more updates

Related Summaries

Heavy menstrual bleeding

Endometrial ablation

Polycystic ovary syndrome

Hysterectomy

Uterine leiomyoma

Overview

terminology describing abnormaluterinebleeding varies widely

initial evaluation of women presenting with abnormaluterinebleeding

history should include

specific details of bleeding pattern

assessment for possible inherited systemic disorders of hemostasis (Kaiser Level A)

testing to consider for all women with abnormaluterinebleeding

pregnancy test (Kaiser Level C)

complete blood count (CBC) (Kaiser Level C)

additional testing guided by patient history and response to treatment

endometrial sampling if increased risk of endometrial hyperplasia or neoplasia (Kaiser Level A)

thyroid-stimulating hormone (TSH) if suspected anovulatory bleeding (Kaiser Level C)

endocrine studies if suspected hyperprolactinemia or hyperandrogenic state

factor VIII platelets and bleeding time if suspected bleeding disorder

further evaluation with ultrasound saline infusion sonography andor hysteroscopy for persistent bleeding (Kaiser Level A)

treatment for acute severe bleeding

IV conjugated equine estrogen 25 mg (repeated at 3-4 hours if needed) may terminate endometrial bleeding in patients with

dysfunctional uterinebleeding (level 2 [mid-level] evidence)

oral medroxyprogesterone acetate and combination oral contraceptives appear equally effective in terminating acute

uterinebleeding (level 2 [mid-level] evidence)

treatment for women with irregular uterinebleeding

progestogens given alone (cyclically continuously or nearly continuously) or in combination with estrogens have limited

evidence for management of anovulatory irregular bleeding (Kaiser Level B)

metformin may reduce menstrual abnormalities in women with polycystic ovarian syndrome (level 2 [mid-level] evidence)

consider stress reduction and weight loss (Kaiser Level C)

surgical therapy for women not interested in preserving fertility (Kaiser Level C)

endometrial ablation is almost as effective as hysterectomy for dysfunctional uterinebleeding (level 1 [likely reliable]

evidence)

for patients with abnormaluterinebleeding due to leiomyomas surgical management determined by size location and

number of myomas (Kaiser Level C)

treatment for heavy menstrual bleeding

clarifying values and patient preferences may reduce hysterectomy rates for menorrhagia (level 2 [mid-level] evidence)

levonorgestrel-releasing intrauterine system (LNG-IUS)

appears effective for heavy menstrual bleeding (level 2 [mid-level] evidence)

improves quality of life as effectively as surgery (level 1 [likely reliable] evidence)

treatment of choice if hormonal treatments are acceptable and at least 12 months use anticipated (NICE A

recommendation)

combined oral contraceptives is second-line drug treatment option (NICE B recommendation)

other medical options include nonsteroidal anti-inflammatory drugs (NSAID) tranexamic acid (Lysteda) oral or injected

progestins and danazol

endometrial ablation preferable to hysterectomy in women with heavy menstrual bleeding alone and uterus le 10 week

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pregnancy size (NICE A recommendation)

for women with large fibroids and other significant symptoms (such as dysmenorrhea or pressure symptoms) consider

surgery or uterine artery embolization as first-line treatment (NICE D(GPP) recommendation)

dilation and curettage (DampC) should not be used as therapeutic treatment (NICE C recommendation)

Description

Also called

IncidencePrevalence

Complications

Pregnancy-related

Hormonal causes

Medications

General Information

abnormaluterinebleeding includes(2)

infrequent unpredictable irregular bleeding that varies in amount duration and character (anovulatory bleeding)

heavy menstrual bleeding (flow gt 80 mL menses which last ge 7 days or have intervals le 21 days)

normal menstrual flow

usual duration of menstrual flow is 4-6 days with average volume blood loss 30 mL (Acta Obstet Gynecol Scand

196645(3)320)

15 of cycles in women of reproductive age are 28 days in length lt 1 have cycle lt 21 days or gt 35 days (Br J

Obstet Gynaecol 1992 May99(5)422)

common terms used include

abnormal vaginal bleeding

dysfunctional uterinebleeding (DUB)

functional uterinebleeding

irregular menstrual bleeding

prolonged menstrual bleeding

extensive disagreement worldwide in terminology describing symptoms signs and causes of abnormaluterinebleeding (Fertil Steril

2008 Dec90(6)2269 Curr Opin Obstet Gynecol 2007 Dec19(6)591)

10-30 prevalence of abnormaluterinebleeding among women of reproductive age (Value Health 2007 May-Jun10(3)183

EBSCOhost Full Text)

anemia including iron deficiency anemia(2)

Differential Diagnosis

pregnancy (see also Pregnancy testing)(2)

ectopic pregnancy(2)

miscarriage(2)

gestational trophoblastic disease(2)

irregular bleeding due to physiologic anovulatory cycles(1 2)

within 2 years of menarche (secondary to immature hypothalamic-pituitary-ovarian axis)

perimenopausal women

hypothyroidism(1 2)

hyperthyroidism(1 2)

hyperprolactinemia(1 2)

hyperandrogenic conditions(1 2)

polycystic ovarian syndrome (PCOS)

congenital adrenal hyperplasia

androgen-producing tumor such as Sertoli-Leydig cell tumor

premature ovarian failure(2)

hypothalamic dysfunction (including anorexia nervosa)(2)

contraception(1)

oral contraceptives

medroxyprogesterone acetate

intrauterine device (IUD)

(1)

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Gynecologic lesions

Bleeding disorders

History

contraception(1)

oral contraceptives

medroxyprogesterone acetate

intrauterine device (IUD)

anticoagulants(2)

phenytoin(1)

antipsychotics (for example olanzapine risperidone)(1)

tricyclic antidepressants(1)

corticosteroids

tamoxifen(2)

herbal supplements with estrogenic activity(2)

vaginal(2)

genital ulcers

squamous cell carcinoma of vagina

cervical(2)

ulcer

cervical polyp

squamous cell carcinoma of cervix

uterine(2)

leiomyoma (fibroids) most common

endometrial adenocarcinoma endometrial sarcoma

endometrial hyperplasia

endometritis

adenomyomata or diffuse adenomyosis

endometrial polyp

congenital abnormalities

genital trauma(2)

foreign bodies(2)

anticoagulants(2)

von Willebrand disease(2)

other blood dyscrasias(2)

inherited bleeding disorders (most commonly von Willebrand disease) reported in 11-17 women with menorrhagia

cohort of 150 women referred for menorrhagia who had normal pelvic exam

women had measurements of activated partial thromboplastin time factor VIII activity von Willebrand factor antigen

and activity and factor XI

26 (17) had inherited bleeding disorder including

von Willebrand disease in 18

factor XI deficiency in 4

combined von Willebrand disease and factor XI deficiency in 1

combined von Willebrand disease factor XI deficiency and factor X deficiency in 1

hemophilia A carrier in 1

platelet dysfunction in 1

Reference - Lancet 1998 Feb 14351(9101)485 EBSCOhost Full Text

comparing 121 women with menorrhagia vs 123 controls

bleeding disorders diagnosed in 107 vs 32 (p = 002)

von Willebrand disease diagnosed in 8 (66) vs 1 (08) (p = 002)

prevalence of von Willebrand disease 159 white patients vs 14 black patients (p = 001)

Reference - Obstet Gynecol 2001 Apr97(4)630

History and Physical

women with heavy uterinebleeding should have a structured history to screen for inherited systemic disorders of hemostasis

(Kaiser Level A)(3)

patients with positive screening on structured history should be considered for further evaluation including consultation with a

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Physical

Testing overview

hematologist andor testing for von Willebrand disease

positive screen defined as any of

heavy menstrual bleeding since menarche

postpartum hemorrhage

surgery related bleeding

bleeding associated with dental work

2 or more of

family history of bleeding symptoms

bruising 1-2 timesmonth

epistaxis 1-2 timesmonth

frequent gum bleeding

each patient with chronic abnormaluterinebleeding should be assessed for ovulatory function (can be reliably confirmed with a

history of predictable cyclic menses with a cycle length of every 22-35 days) (Kaiser Level C)(3)

determine pattern of bleeding(1)

severe acute bleeding (bleeding requiring gt 1 pad or tampon per hour or vital signs indicating hypovolemia)

irregular bleeding (includes metrorrhagia menometrorrhagia oligomenorrhea prolonged bleeding intermenstrual bleeding

or other irregular pattern)

menorrhagia (heavy but regular cyclic bleeding plus gt 7 days of bleeding or clots or iron deficiency anemia) prolonged

bleeding gt 12 days should be considered irregular regardless of cyclic pattern

ask about

symptoms of anemia (fatigue lightheadedness weakness dyspnea on exertion)(2)

history of weight change(2)

history or symptoms of thyroid disorder(2)

medication use(2)

oral contraceptive

thyroid medications

other hormones

anticoagulants

check for signs of(2)

pregnancy

anemia (pallor tachycardia)

endocrine disorders

hyperandrogenism (acne hirsutism virilization)

hypothyroidism

hyperthyroidism

bleeding disorder (petechiae bruising recurrent or unexplained joint effusion)

abdominal mass (if large uterine fibroid)

gynecological exam for structural lesions(2)

vaginal

genital ulcers

squamous cell carcinoma of vagina

cervical

ulcer

polyp

squamous cell carcinoma of cervix

uterine

leiomyoma (fibroids) most common

endometrial adenocarcinoma endometrial sarcoma

endometritis

adenomyomata or diffuse adenomyosis

polyp

congenital abnormalities

Diagnostic Testing

for all women with chronic abnormaluterinebleeding(3)

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Endometrial sampling

Imaging studies

pregnancy test (urine or blood) should be done (Kaiser Level C)

CBC should be considered (Kaiser Level C)

additional testing guided by patient history(3)

TSH is appropriate in women with suspected or known anovulatory dysfunctional uterinebleeding (DUB) (Kaiser Level C)

endometrial sampling if increased risk of endometrial hyperplasia or neoplasia (Kaiser Level A)

other endocrine tests if indicated

to rule out hyperprolactinemia - prolactin level

to rule out polycystic ovary syndrome or other hyperandrogenic state

17-hydroxyprogesterone

testosterone

dehydroepiandrosterone sulfate

testing for bleeding disorder if bleeding persists despite treatment(3)

platelets

bleeding time

factor VIII

routine transvaginal ultrasonography generally unnecessary for initial visit but should be considered for persisting symptoms and

especially for those who fail initial medical therapy (Kaiser Level C)(3)

indications for further evaluation with ultrasound saline infusion sonography andor hysteroscopy (Kaiser Level A) include(3)

persistent abnormaluterinebleeding despite normal and satisfactory endometrial sampling

irregular thickening of endometrium on ultrasound (suggesting presence of focal lesions)

endometrial cavity cannot be identified in its entirety

if polyps or fibroids involving endometrial cavity suspected

indications for endometrial sampling

endometrial sampling should be performed when there is an increased risk of endometrial hyperplasia or neoplasia (Kaiser

Level A)

women aged gt 40 years (Kaiser Level B)

women aged lt 40 years with additional risk factors (including features suggestive of chronic anovulation and weight greater

than 90 kg) (Kaiser Level B)

patients with a family history of hereditary nonpolyposis colorectal cancer syndrome (Lynch Syndrome) (Kaiser Level B)

sampling approach

outpatient endometrial biopsy with catheter techniques should be considered first line approach (Kaiser Level A)

if endometrial biopsy is indicated and cannot be obtained or is inadequate repeat sampling should be attempted if

necessary with DampC (Kaiser Level C)

Pipelle and Explora curettes associated with similar patient pain ratings in endometrial biopsy (level 2 [mid-

level] evidence)

based on randomized trial with use of means instead of medians for pain analysis

70 women having endometrial biopsy (abnormaluterinebleeding most common indication) randomized to Pipelle vs Explora

curette

no significant difference in subject-reported pain or provider-reported ease of use

Reference - Obstet Gynecol 2011 Mar117(3)636

review of evaluation of the endometrium can be found in Obstet Gynecol 2010 Jul116(1)168

considerations for imaging of endometrial cavity(3)

goals for evaluation of endometrial cavity in women with chronic abnormaluterinebleeding include detection of endometrial

hyperplasia or cancer in selected patients and identification of focal lesions such as polyps and leiomyomas (fibroids) which

might explain bleeding (Kaiser Level C)

if chronic abnormaluterinebleeding continues despite normal and satisfactory endometrial sampling consider ultrasound

saline infusion sonography andor hysteroscopy (Kaiser Level A)

transvaginal ultrasound considered adequate if entire endometrial echo shown in longitudinal and transverse planes through

widest part of endometrial cavity (Kaiser Level C)

no consensus on upper limit of endometrial thickness to be considered normal in premenopausal women (Kaiser Level B)

transvaginal ultrasound considered good screening test but may miss some focal lesions such as polyps (Kaiser Level B)

transvaginal ultrasound sonohysterography and hysteroscopy may be similarly effective in detection of

intrauterine pathology in premenopausal women with abnormaluterinebleeding (level 2 [mid-level] evidence)

based on systematic review with heterogeneity

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Acute severe bleeding

19 prospective cohort studies reviewed including 2917 patients 408 (25) postmenopausal

for detection of any intrauterine pathology statistically significant heterogeneity prevented pooling of likelihood ratios

for detection of submucous fibroids

sonohysterography had pooled likelihood ratio 297 (95 CI 178-496)

hysteroscopy had pooled likelihood ratio 294 (95 CI 134-653)

pooled likelihood ratio for transvaginal ultrasound not calculated because of statistically significant heterogeneity

Reference - Acta Obstet Gynecol Scand 2003 Jun82(6)493 EBSCOhost Full Text

prophylactic vaginal misoprostol may reduce pain in women having outpatient hysteroscopy (level 2 [mid-

level] evidence)

based on randomized trial with allocation concealment not stated

150 women having outpatient hysteroscopy for diagnosis of infertility or abnormaluterinebleeding randomized to cervical

priming with misoprostol 200 mcg vaginally 3 hours before procedure vs no misoprostol

comparing misoprostol vs no misoprostol

mean pain scores (on 0-10 visual analog scale) 326 vs 487 (p lt 0001)

mean procedure time 2 minutes vs 25 minutes (p lt 0001)

misoprostol associated with increased ease of cervical entry and patient acceptability (p le 002 for each)

Reference - Fertil Steril 2011 Oct96(4)962

American Institute of Ultrasound in Medicine (AIUM) guideline on pelvic ultrasound examinations can be found in J Ultrasound

Med 2010 Jan29(1)166

review of evaluation of the endometrium can be found in Obstet Gynecol 2010 Jul116(1)168

Management

indications for hospitalization(1)

orthostatic hypotension

hemoglobin lt 10 gdL

profuse active bleeding

consider blood transfusion if severely anemic(1)

hormonal medication

estrogen

use often recommended but evidence for efficacy is limited(1 2)

IV conjugated equine estrogen may terminate endometrial bleeding in patients with dysfunctional

uterinebleeding (DUB) (level 2 [mid-level] evidence)

based on small randomized trial

34 patients who presented to emergency room with excessive or prolonged uterinebleeding were randomized to

conjugated estrogens (Premarin) 25 mg vs placebo in 5 mL normal saline injected IV over 2 minutes through IV

line running at 75 mLhour

dose repeated (double-blind Premarin or placebo) at 3 hours if bleeding continued

open-label dose of Premarin (regardless of original assignment) at 5 hours if bleeding continued

alternative treatment provided if bleeding continued at 8 hours

comparing estrogen vs placebo

mean duration of bleeding at presentation 141 days (range 1-78) vs 116 days (range 1-90)

bleeding stopped after first injection in 22 vs 36 (not significant)

bleeding stopped after first or second injection in 72 vs 38 (p = 0021 NNT 3)

adverse effects in 39 vs 13 (not significant)

Reference - Obstet Gynecol 1982 Mar59(3)285

DynaMed commentary -- patients had range of bleeding history unclear how many had acute severe bleeding

dose schedules suggested in review article(1)

for inpatient management

conjugated equine estrogens 25 mg in normal saline 50 mL given IV over 20 minutes every 4 hours for 24

hours

at same time start tapered dosing of combination oral contraceptive (ethinyl estradiol 30 mcgnorgestrel 03

mg)

for outpatient management

conjugated equine estrogens 25 mg orally 4 times daily

after acute bleeding stopped start tapered dosing of combination oral contraceptive (ethinyl estradiol 30

mcgnorgestrel 03 mg)

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Irregular menstrual bleeding

tapered dose schedule

1 tablet 4 times daily for 4 days then

1 tablet 3 times daily for 3 days then

1 tablet twice daily for 2 days then

1 tablet once daily for 3 weeks then

1 week off then cycle of oral contraceptives for at least 3 months

oral medroxyprogesterone acetate and combination oral contraceptives appear equally effective in

terminating acute uterinebleeding (level 2 [mid-level] evidence)

based on small randomized trial

40 hemodynamically stable patients with acute uterinebleeding (defined as sufficient to justify immediate medical or

surgical intervention) randomized to

medroxyprogesterone acetate 20 mg orally 3 times daily for 1 week then 20 mg once daily for 3 weeks

monophasic combination oral contraceptive containing norethindrone 1 mg plus ethinyl estradiol 35 mcg 1 tablet 3

times daily for 1 week then 1 tablet once daily for 3 weeks

33 patients (82) evaluated at 14 days

comparing medroxyprogesterone acetate vs combination oral contraceptive

cessation of bleeding achieved in 76 vs 88 (not significant)

median time to bleeding cessation 3 days vs 3 days

emergency surgical procedures avoided in 100 vs 95

no significant differences in incidence of treatment-related nausea and bloating

Reference - Obstet Gynecol 2006 Oct108(4)924

indications for dilatation and curettage or intrauterine Foley bulb placement(1 2)

hemodynamic instability and acute bleeding

lack of response to initial

2 doses of IV estrogen (if inpatient)

4 doses of oral estrogen (if outpatient)

evaluation once patient stabilized(1)

investigation for bleeding disorder (complete blood count platelet count prothrombin time activated partial thromboplastin

time platelet function analysis)

transvaginal ultrasound

medical therapy for irregular menstrual bleeding (presumed anovulatory)

empiric medical management can be started(2)

goal of treatment is to restore natural cycle of endometrial growth and shedding

withdrawal bleeding can be induced by progestin (medroxyprogesterone acetate 5-10 mg daily for 2 weeks every

month)

progestogens given alone (cyclically continuously or nearly continuously) or in combination with estrogens have limited

evidence for management of anovulatory irregular bleeding (Kaiser Level B)(3)

continuing therapy for at least 3 months after stabilization has been suggested for irregular bleeding in nonpregnant

women(1)

no randomized trials found evaluating progestogens alone or in combination with estrogens for irregular or

heavy menstrual bleeding due to anovulation

based on Cochrane review

Reference - Cochrane Database Syst Rev 2012 Sep 12(9)CD001895

metformin and other insulin-sensitizing drugs

role of metformin and other hypoglycemic agents for routine treatment of chronic anovulatory abnormaluterinebleeding

has not been established (Kaiser Level B)(3)

metformin may reduce menstrual abnormalities in women with polycystic ovarian syndrome (PCOS)

metformin may improve menstrual regularity (level 2 [mid-level] evidence) and hormonal markers

(level 3 [lacking direct] evidence) in normal weight normoinsulinemic women with PCOS

based on small randomized trial

28 normal-weight normoinsulinemic women with PCOS randomized to metformin 500 mg twice daily vs

placebo

metformin significantly associated with improved

testosterone levels at 3 and 6 months

17-hydroxyprogesterone levels at 6 months

hirsutism score at 6 months

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reduced ovarian volume at 3 and 6 months

70 in metformin group experienced restoration of menstrual cyclicity

no clinical or hormonal changes with placebo

Reference - Fertil Steril 2010 May 193(7)2303

metformin 850 mg twice daily does not appear to improve menstrual frequency or insulin sensitivity

in obese women with PCOS already making weight loss lifestyle changes (level 2 [mid-level]

evidence)

based on randomized trial with allocation concealment not stated

143 obese oligo-amenorrheic women with PCOS received dietary plan and were randomized to metformin

850 mg twice daily vs placebo for 6 months

metformin significantly reduced waist circumference and free androgen index

no significant difference in

menstrual frequency (both groups improved)

insulin sensitivity

lipid profiles

Reference - Hum Reprod 2006 Jan21(1)80 full-text

metformin may reduce markers of PCOS and menstrual abnormalities

based on small randomized trial

23 women with PCOS randomized to metformin 500 mg vs placebo orally 3 times daily for 6 months

metformin reduced menstrual abnormalities plasma insulin insulin resistance and ovarian hyperandrogenism

no changes in placebo group

warning that ovulation may resume and contraception may be necessary

Reference - J Clin Endocrinol Metab 2000 Jan85(1)139 in Prescribers Letter 2000 Mar7(3)16

metformin associated with higher rate of menses

based on 12-week randomized placebo-controlled trial with 22 patients aged 13-18 years with hyperinsulinemia

and PCOS

Reference - Arch Pediatr Adolesc Med 2006 Mar160(3)241 commentary can be found in Am Fam Physician

2006 Sep 174(5)862

metformin 500-1000 mg twice daily may improve menstrual cyclicity and quality of life in oligo-

amenorrheic women with PCOS (level 2 [mid-level] evidence)

based on cohort study of 64 women (mean age 29 years) with PCOS (all oligoamenorrheic) having

metformin 500-1000 mg twice daily (depending on weight) for 6 months

metformin associated with

normalized menstrual cycle (52 achieved 28-35 cycles)

improved quality of life scores (including domains of vitality social function mental and sexual health)

significant baseline reductions in

insulin resistance

testosterone levels (55 achieved normal levels)

free androgen index levels

body mass index (BMI) (mean decrease 11 kgm )2

no difference in alopecia or hirsutism scores

Reference - Hum Reprod 2006 Jul21(7)1925 full-text

ovulation induction is not indicated (Kaiser Level C)(3)

gonadotropin-releasing hormone (GnRH) agonists may have a role in management of selected women with chronic

anovulatory abnormaluterinebleeding (Kaiser Level B)(3)

lifestyle issues including stress reduction and weight loss might be important in management of abnormaluterinebleeding

associated with anovulatory state (Kaiser Level C)(3)

surgical therapy

surgical therapy for women with chronic dysfunctional uterinebleeding (DUB) is currently reserved for women not interested

in future fertility (Kaiser Level C)(3)

hysterectomy is more effective than endometrial ablation for resolution of symptoms of DUB but has more

adverse perioperative events (level 1 [likely reliable] evidence)

based on randomized trial

237 premenopausal women aged ge 18 years with dysfunctional uterinebleeding randomized to endometrial ablation vs

hysterectomy and followed for up to 5 years

85 were aged lt 45 years

due to funding concerns trial terminated early but gt 80 of women were followed for at least 2 years

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Heavy menstrual bleeding (menorrhagia)

Other management

primary outcome was resolution of the major reason for which women sought treatment (bleeding pain or fatigue)

comparing endometrial ablation vs hysterectomy

879 vs 932 had major problem solved at 1 year

849 vs 944 had major problem solved at 2 years (p = 0026 NNT 11 favoring hysterectomy)

933 vs 951 had major problem solved at 3 years

851 vs 98 had major problem solved at 4 years (p = 0026 NNT 8 favoring hysterectomy)

109 vs 406 had adverse perioperative events (NNT 4 favoring endometrial ablation)

29 (32 of 110 women) with endometrial ablation required reoperation by 48 months

Reference - STOP-DUB trial (Obstet Gynecol 2007 Dec110(6)1279) correction can be found in Obstet Gynecol 2008

Aug112(2 Pt 1)381 commentary can be found in Obstet Gynecol 2008 Apr111(4)992

for patients with abnormaluterinebleeding due to leiomyomas(3)

surgical management of abnormaluterinebleeding due to leiomyomas is determined by size location and number of

myomas (Kaiser Level C)

selected patients with leiomyoma-related abnormaluterinebleeding who do not wish to retain fertility may be considered

for endometrial ablation (Kaiser Level A)

abdominal myomectomy is the preferred procedure for women with abnormaluterinebleeding related to myomas

unsuitable for resectoscopic removal and who wish to retain their uterus (Kaiser Level C)

symptomatic endometrial polyps should be completely removed under hysteroscopic direction (Kaiser Level B)(3)

improvement in quality of life measures should be goal of any interventions (NICE D recommendation)

clarifying values and patient preferences may reduce hysterectomy rates for menorrhagia (level 2 [mid-level] evidence)

medications

levonorgestrel intrauterine system (LNG-IUS) appears effective for heavy menstrual bleeding (level 2 [mid-level] evidence)

and is treatment of choice if (NICE A recommendation)

hormonal treatments are acceptable

at least 12 months use anticipated

combined oral contraceptives is second-line drug treatment option (NICE B recommendation)

either NSAID or tranexamic acid (Lysteda) considered

second-line treatment option if either hormonal or nonhormonal treatments are acceptable (NICE A recommendation)

preferred treatment option if hormonal treatments are not acceptable (NICE D(GPP) recommendation)

tranexamic acid should not be used before LNG-IUS if long-term use is anticipated (NICE A recommendation)

oral progestins (such as norethisterone 15 mg once daily on menstrual cycle days 5-26) or injected long-acting progestins

considered third-line treatment options (NICE A recommendation)

danazol may be effective for heavy menstrual bleeding (level 2 [mid-level] evidence)

surgeryprocedures

surgery reduces menstrual bleeding at 1 year more than medical therapy but levonorgestrel-intrauterine system improves

quality of life as effectively as surgery (level 1 [likely reliable] evidence)

endometrial ablation

preferable to hysterectomy in women with heavy menstrual bleeding alone and uterus le 10 week pregnancy size

(NICE A recommendation)

preprocedure endometrial thinning may improve operative conditions and amenorrhea at 12 months (level 2 [mid-level]

evidence)

referral for consideration of surgery or uterine artery embolization (UAE) as first-line treatment recommended for women

with large fibroids and heavy menstrual bleeding and other significant symptoms such as dysmenorrhea or pressure

symptoms (NICE D(GPP) recommendation)

UAE myomectomy or hysterectomy should all be considered discussed and documented when surgery for fibroid-related

heavy menstrual bleeding is considered necessary (NICE D(GPP) recommendation)

vaginal hysterectomy preferred over abdominal hysterectomy after incorporating individual assessment (NICE A

recommendation)

DampC should not be used as therapeutic treatment (NICE C recommendation)

see Heavy menstrual bleeding for treatment details

assess need for iron therapy

therapy should be individualized

if needed see Iron deficiency anemia in adults

insufficient evidence for evaluation of use of Chinese herbal medication for dysfunctional uterinebleeding (DUB)

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Guidelines

United States guidelines

United Kingdom guidelines

Canadian guidelines

European guidelines

Mexican guidelines

Review articles

based on meta-analysis

all except one trial had poor methodological quality

Reference - Evid Based Complement Alternat Med 2009 Mar6(1)99 full-text

Guidelines and Resources

American College of Obstetricians and Gynecologists (ACOG) guidelines

American College of Obstetricians and Gynecologists (ACOG) Practice Bulletin 128 on diagnosis of abnormaluterinebleeding

in reproductive-aged women can be found in Obstet Gynecol 2012 Jul120(1)197 or at National Guideline Clearinghouse

2013 Feb 1138623 commentary can be found in ACOG News Release 2012 Jun 21

American College of Obstetricians and Gynecologists (ACOG) Committee Opinion 557 on management of acute

abnormaluterinebleeding in nonpregnant reproductive-aged women can be found in Obstet Gynecol 2013 Apr121(4)891

ACOG Practice Bulletin 136 on management of abnormaluterinebleeding associated with ovulatory dysfunction can be

found in Obstet Gynecol 2013 Jul122(1)176 or at National Guideline Clearinghouse 2014 Feb 1747451

ACOG Practice Bulletin 81 on endometrial ablation can be found in Obstet Gynecol 2007 May109(5)1233 reaffirmed 2012

Feb or at National Guideline Clearinghouse 2007 Dec 2410918

ACOG Committee Opinion 349 on menstruation on girls and adolescents can be found in Obstet Gynecol 2006

Nov108(5)1323 reaffirmed 2009 Jun also produced by American Academy of Pediatrics (Pediatrics 2006

Nov118(5)2245)

American College of Radiology (ACR) Appropriateness Criteria for abnormal vaginal bleeding can be found at ACR 2010 PDF or

at National Guideline Clearinghouse 2011 Sep 532629

Society of Gynecologic Surgeons (SGS) clinical practice guideline on abnormaluterinebleeding hysterectomy versus alternative

therapy can be found in J Minim Invasive Gynecol 2012 Jan-Feb19(1)81

American College of RadiologyAmerican College of Obstetricians and GynecologistsAmerican Institute of Ultrasound in Medicine

(ACRACOGAIUM) guideline on performance of sonohysterography can be found in J Ultrasound Med 2012 Jan31(1)165 full-

text or at ACRACOGAIUM 2011 PDF

National Institute for Health and Clinical Excellence (NICE) guideline on

heavy menstrual bleeding can be found in NICE 2007 JanCG44 PDF

fluid-filled thermal balloon and microwave endometrial ablation techniques for heavy menstrual bleeding can be found at

NICE 2004 AprTA78

Royal College of Obstetricians and Gynaecologists (RCOG) guideline on best practice in outpatient hysteroscopy can be found

at RCOG 2011 Mar PDF or at National Guideline Clearinghouse 2012 May 1434905

Society of Obstetricians and Gynaecologists of Canada (SOGC) guideline on abnormaluterinebleeding in pre-menopausal women

can be found at SOGC 2013 May 23 PDF or at National Guideline Clearinghouse 2014 Jan 646416

Society of Obstetricians and Gynaecologists of Canada (SOGC) clinical guideline on female sexual health consensus can be

found at SOGC 2012 PDF or at National Guideline Clearinghouse 2013 Jun 338474

Society of Obstetricians and Gynaecologists of Canada (SOGC) recommendations on asymptomatic endometrial thickening can

be found in J Obstet Gynaecol Can 2010 Oct32(10)990 PDF

Alberta Health Services (AHS) clinical practice guideline on uterine sarcoma can be found at AHS 2011 Aug PDF or at National

Guideline Clearinghouse 2013 Mar 438596

Collegravege National des Gyneacutecologues et Obsteacutetriciens Franccedilais (CNGOF) clinical practice guideline on menorrhagia management of

abnormaluterinebleeding before menopause can be found in Eur J Obstet Gynecol Reprod Biol 2010 Oct152(2)133

Mexican School of Obstetrics and Gynecology (Colegio Mexicano de Especialistas en Ginecologa y Obstetricia) clinical practice

guideline on dysfunctional uterinebleeding can be found in Ginecol Obstet Mex 2009 Sep77(9)S231 EBSCOhost Full Text

[Spanish]

review can be found in Am Fam Physician 2004 Apr 1569(8)1915

review can be found in Postgrad Med 2001 Jan109(1)137

review can be found in Am Fam Physician 1999 Oct 160(5)1371

review of managing unscheduled bleeding in non-pregnant premenopausal women can be found in BMJ 2013 Jun 4346f3251

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ICD-9 codes

ICD-10 codes

General references used

Recommendation grading systems used

AHRQ Comparative Effectiveness Review on primary care management of abnormaluterinebleeding 2013 Mar96 PDF

review of abnormaluterinebleeding in premenopausal women can be found in Am Fam Physician 2012 Jan 185(1)35

EBSCOhost Full Text

reviews of terminology controversy can be found in Fertil Steril 2008 Dec90(6)2269 Curr Opin Obstet Gynecol 2007

Dec19(6)591

review of treatment of dysfunctional uterinebleeding can be found in Maturitas 2004 Mar 1547(3)159

review of health-related quality of life work impairment and health-care costs and utilization in abnormaluterinebleeding can be

found in Value Health 2007 May-Jun10(3)183 EBSCOhost Full Text

Patient Information

handout from American College of Obstetricians and Gynecologists PDF

handout from American Society for Reproductive Medicine PDF

handout from American Academy of Family Physicians or in Spanish

handout on dysfunctional uterinebleeding from TeensHealth or in Spanish

technical information on dysfunctional uterinebleeding from Patient Plus PDF

handout on reasons for problem bleeding from Cleveland Clinic

handout on vaginal bleeding from Mayo Clinic

handout on dysfunctional uterinebleeding questions to discuss with your doctor from Harvard Medical School

ICD-9ICD-10 Codes

6262 excessive or frequent menstruation

6263 puberty bleeding

6264 irregular menstrual cycle

6265 ovulation bleeding

6266 metrorrhagia

6267 postcoital bleeding

6268 other disorders of menstruation and other abnormalbleeding from female genital tract

6269 unspecified disorders of menstruation and other abnormalbleeding from female genital tract

N92 excessive frequent and irregular menstruation

N920 excessive and frequent menstruation with regular cycle

N921 excessive and frequent menstruation with irregular cycle

N922 excessive menstruation at puberty

N923 ovulation bleeding

N924 excessive bleeding in the premenopausal period

N925 other specified irregular menstruation

N926 irregular menstruation unspecified

N93 other abnormaluterine and vaginal bleeding

N930 postcoital and contact bleeding

N938 other specified abnormaluterine and vaginal bleeding

N939 abnormaluterine and vaginal bleeding unspecified

References

1 Ely JW Kennedy CM Clark EC Bowdler NC Abnormaluterinebleeding a management algorithm J Am Board Fam Med

2006 Nov-Dec19(6)590-602 full-text

2 Casablanca Y Management of dysfunctional uterinebleeding Obstet Gynecol Clin North Am 2008 Jun35(2)219-34 viii

3 Amann M Anguino H Bauman RA et al Chronic abnormaluterinebleeding in nongravid women Pasadena (CA) Kaiser

Permanente Southern California National Guideline Clearinghouse 2007 Oct 2910889

4 National Collaborating Centre for Womenrsquos and Childrenrsquos Health Heavy menstrual bleeding National Institute for Health and

Clinical Excellence (NICE) 2007 JanCG44 PDF

Kaiser Permanente Southern California uses American College of Obstetricians and Gynecologists (ACOG) strength of

recommendation classification

grades of recommendation

Level A - based on good and consistent scientific evidence

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DynaMed editorial process

Special acknowledgements

How to cite

Level B - based on limited or inconsistent scientific evidence

Level C - based primarily on consensus and expert opinion

Reference - Kaiser Permanente Southern California guideline on chronic abnormaluterinebleeding in nongravid women

(National Guideline Clearinghouse 2007 Oct 2910889)

National Institute for Health and Clinical Excellence (NICE) grading system for recommendations

Grade A

at least 1 meta-analysis systematic review or randomized controlled trial (RCT) that is rated 1++ and is directly

applicable to target population or

systematic review of RCTs or body of evidence that consists principally of studies rated 1+ is directly applicable to

target population and demonstrates overall consistency of results or

evidence drawn from NICE technology appraisal

Grade B

body of evidence that includes studies rated 2++ is directly applicable to target population and demonstrates overall

consistency of results or

extrapolated evidence from studies rated 1++ or 1+

Grade C

body of evidence that includes studies rated 2++ is directly applicable to target population and demonstrates overall

consistency of results or

extrapolated evidence from studies rated 2++

Grade D

evidence level 3 or 4 or

extrapolated evidence from studies rated 2+ or

formal consensus

Grade D (GPP) - a good practice point (GPP) is a recommendation for best practice based on experience of Guideline

Development Group

levels of evidence for intervention studies

1++ includes high-quality meta-analyses systematic reviews of RCTs or RCTs with very low risk of bias

1+ includes well-conducted meta-analyses systematic reviews of RCTs or RCTs with low risk of bias

1- includes meta-analyses systematic reviews of RCTs or RCTs with high risk of bias

2++ includes high-quality systematic reviews of case-control or cohort studies high-quality case-control or cohort

studies with very low risk of confounding bias or chance and high probability relationship is casual

2+ includes well-conducted case-control or cohort studies with low risk of confounding bias or chance and moderate

probability relationship is casual

2- includes case-control or cohort studies with high risk of confounding bias or chance and significant risk relationship is

not casual

3 includes nonanalytical studies (for example case reports case series)

4 includes expert opinion formal consensus

Reference - NICE guideline on heavy menstrual bleeding (NICE 2007 JanCG44 PDF)

DynaMed topics are created and maintained by the DynaMed Editorial Team

Over 500 journals and evidence-based sources (DynaMed Content Sources) are monitored directly or indirectly using a 7-Step

evidence-based method for systematic literature surveillance DynaMed topics are updated daily as newly discovered best

available evidence is identified

The participating members of the DynaMed Editorial Team have declared that they have no financial or other competing

interests related to this topic

The participating reviewers have declared that they have no financial or other competing interests related to this topic unless

otherwise indicated

McMaster University is a partner that provides support in identifying Practice-Changing DynaMed Updates Over 1000 practicing

physicians from 61 disciplines in 77 countries rate these articles to help you find the most useful new evidence affecting your

practice

F1000 is a partner that provides support in identifying Practice-Changing DynaMed Updates Over 2000 practicing clinicians from

20 disciplines in 60 countries rate these articles to help you find the most useful new evidence affecting your practice

Linda Feng Chang PharmD MPH BCPS (EPC Course Director and Clinical Assistant Professor of Pharmacy University of Illinois

College of Medicine Illinois United States) provides peer review

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copy 2014 EBSCO Industries Inc Todos los derechos reservados

Page 2: Abnormal uterine bleeding - AEEMmedicina-ucr.com/.../2014/04/Abnormal-Uterine-Bleeding-DynaMed.pdf · Abnormal uterine bleeding ... endometrial ablation preferable to hysterectomy

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pregnancy size (NICE A recommendation)

for women with large fibroids and other significant symptoms (such as dysmenorrhea or pressure symptoms) consider

surgery or uterine artery embolization as first-line treatment (NICE D(GPP) recommendation)

dilation and curettage (DampC) should not be used as therapeutic treatment (NICE C recommendation)

Description

Also called

IncidencePrevalence

Complications

Pregnancy-related

Hormonal causes

Medications

General Information

abnormaluterinebleeding includes(2)

infrequent unpredictable irregular bleeding that varies in amount duration and character (anovulatory bleeding)

heavy menstrual bleeding (flow gt 80 mL menses which last ge 7 days or have intervals le 21 days)

normal menstrual flow

usual duration of menstrual flow is 4-6 days with average volume blood loss 30 mL (Acta Obstet Gynecol Scand

196645(3)320)

15 of cycles in women of reproductive age are 28 days in length lt 1 have cycle lt 21 days or gt 35 days (Br J

Obstet Gynaecol 1992 May99(5)422)

common terms used include

abnormal vaginal bleeding

dysfunctional uterinebleeding (DUB)

functional uterinebleeding

irregular menstrual bleeding

prolonged menstrual bleeding

extensive disagreement worldwide in terminology describing symptoms signs and causes of abnormaluterinebleeding (Fertil Steril

2008 Dec90(6)2269 Curr Opin Obstet Gynecol 2007 Dec19(6)591)

10-30 prevalence of abnormaluterinebleeding among women of reproductive age (Value Health 2007 May-Jun10(3)183

EBSCOhost Full Text)

anemia including iron deficiency anemia(2)

Differential Diagnosis

pregnancy (see also Pregnancy testing)(2)

ectopic pregnancy(2)

miscarriage(2)

gestational trophoblastic disease(2)

irregular bleeding due to physiologic anovulatory cycles(1 2)

within 2 years of menarche (secondary to immature hypothalamic-pituitary-ovarian axis)

perimenopausal women

hypothyroidism(1 2)

hyperthyroidism(1 2)

hyperprolactinemia(1 2)

hyperandrogenic conditions(1 2)

polycystic ovarian syndrome (PCOS)

congenital adrenal hyperplasia

androgen-producing tumor such as Sertoli-Leydig cell tumor

premature ovarian failure(2)

hypothalamic dysfunction (including anorexia nervosa)(2)

contraception(1)

oral contraceptives

medroxyprogesterone acetate

intrauterine device (IUD)

(1)

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Gynecologic lesions

Bleeding disorders

History

contraception(1)

oral contraceptives

medroxyprogesterone acetate

intrauterine device (IUD)

anticoagulants(2)

phenytoin(1)

antipsychotics (for example olanzapine risperidone)(1)

tricyclic antidepressants(1)

corticosteroids

tamoxifen(2)

herbal supplements with estrogenic activity(2)

vaginal(2)

genital ulcers

squamous cell carcinoma of vagina

cervical(2)

ulcer

cervical polyp

squamous cell carcinoma of cervix

uterine(2)

leiomyoma (fibroids) most common

endometrial adenocarcinoma endometrial sarcoma

endometrial hyperplasia

endometritis

adenomyomata or diffuse adenomyosis

endometrial polyp

congenital abnormalities

genital trauma(2)

foreign bodies(2)

anticoagulants(2)

von Willebrand disease(2)

other blood dyscrasias(2)

inherited bleeding disorders (most commonly von Willebrand disease) reported in 11-17 women with menorrhagia

cohort of 150 women referred for menorrhagia who had normal pelvic exam

women had measurements of activated partial thromboplastin time factor VIII activity von Willebrand factor antigen

and activity and factor XI

26 (17) had inherited bleeding disorder including

von Willebrand disease in 18

factor XI deficiency in 4

combined von Willebrand disease and factor XI deficiency in 1

combined von Willebrand disease factor XI deficiency and factor X deficiency in 1

hemophilia A carrier in 1

platelet dysfunction in 1

Reference - Lancet 1998 Feb 14351(9101)485 EBSCOhost Full Text

comparing 121 women with menorrhagia vs 123 controls

bleeding disorders diagnosed in 107 vs 32 (p = 002)

von Willebrand disease diagnosed in 8 (66) vs 1 (08) (p = 002)

prevalence of von Willebrand disease 159 white patients vs 14 black patients (p = 001)

Reference - Obstet Gynecol 2001 Apr97(4)630

History and Physical

women with heavy uterinebleeding should have a structured history to screen for inherited systemic disorders of hemostasis

(Kaiser Level A)(3)

patients with positive screening on structured history should be considered for further evaluation including consultation with a

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Physical

Testing overview

hematologist andor testing for von Willebrand disease

positive screen defined as any of

heavy menstrual bleeding since menarche

postpartum hemorrhage

surgery related bleeding

bleeding associated with dental work

2 or more of

family history of bleeding symptoms

bruising 1-2 timesmonth

epistaxis 1-2 timesmonth

frequent gum bleeding

each patient with chronic abnormaluterinebleeding should be assessed for ovulatory function (can be reliably confirmed with a

history of predictable cyclic menses with a cycle length of every 22-35 days) (Kaiser Level C)(3)

determine pattern of bleeding(1)

severe acute bleeding (bleeding requiring gt 1 pad or tampon per hour or vital signs indicating hypovolemia)

irregular bleeding (includes metrorrhagia menometrorrhagia oligomenorrhea prolonged bleeding intermenstrual bleeding

or other irregular pattern)

menorrhagia (heavy but regular cyclic bleeding plus gt 7 days of bleeding or clots or iron deficiency anemia) prolonged

bleeding gt 12 days should be considered irregular regardless of cyclic pattern

ask about

symptoms of anemia (fatigue lightheadedness weakness dyspnea on exertion)(2)

history of weight change(2)

history or symptoms of thyroid disorder(2)

medication use(2)

oral contraceptive

thyroid medications

other hormones

anticoagulants

check for signs of(2)

pregnancy

anemia (pallor tachycardia)

endocrine disorders

hyperandrogenism (acne hirsutism virilization)

hypothyroidism

hyperthyroidism

bleeding disorder (petechiae bruising recurrent or unexplained joint effusion)

abdominal mass (if large uterine fibroid)

gynecological exam for structural lesions(2)

vaginal

genital ulcers

squamous cell carcinoma of vagina

cervical

ulcer

polyp

squamous cell carcinoma of cervix

uterine

leiomyoma (fibroids) most common

endometrial adenocarcinoma endometrial sarcoma

endometritis

adenomyomata or diffuse adenomyosis

polyp

congenital abnormalities

Diagnostic Testing

for all women with chronic abnormaluterinebleeding(3)

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Endometrial sampling

Imaging studies

pregnancy test (urine or blood) should be done (Kaiser Level C)

CBC should be considered (Kaiser Level C)

additional testing guided by patient history(3)

TSH is appropriate in women with suspected or known anovulatory dysfunctional uterinebleeding (DUB) (Kaiser Level C)

endometrial sampling if increased risk of endometrial hyperplasia or neoplasia (Kaiser Level A)

other endocrine tests if indicated

to rule out hyperprolactinemia - prolactin level

to rule out polycystic ovary syndrome or other hyperandrogenic state

17-hydroxyprogesterone

testosterone

dehydroepiandrosterone sulfate

testing for bleeding disorder if bleeding persists despite treatment(3)

platelets

bleeding time

factor VIII

routine transvaginal ultrasonography generally unnecessary for initial visit but should be considered for persisting symptoms and

especially for those who fail initial medical therapy (Kaiser Level C)(3)

indications for further evaluation with ultrasound saline infusion sonography andor hysteroscopy (Kaiser Level A) include(3)

persistent abnormaluterinebleeding despite normal and satisfactory endometrial sampling

irregular thickening of endometrium on ultrasound (suggesting presence of focal lesions)

endometrial cavity cannot be identified in its entirety

if polyps or fibroids involving endometrial cavity suspected

indications for endometrial sampling

endometrial sampling should be performed when there is an increased risk of endometrial hyperplasia or neoplasia (Kaiser

Level A)

women aged gt 40 years (Kaiser Level B)

women aged lt 40 years with additional risk factors (including features suggestive of chronic anovulation and weight greater

than 90 kg) (Kaiser Level B)

patients with a family history of hereditary nonpolyposis colorectal cancer syndrome (Lynch Syndrome) (Kaiser Level B)

sampling approach

outpatient endometrial biopsy with catheter techniques should be considered first line approach (Kaiser Level A)

if endometrial biopsy is indicated and cannot be obtained or is inadequate repeat sampling should be attempted if

necessary with DampC (Kaiser Level C)

Pipelle and Explora curettes associated with similar patient pain ratings in endometrial biopsy (level 2 [mid-

level] evidence)

based on randomized trial with use of means instead of medians for pain analysis

70 women having endometrial biopsy (abnormaluterinebleeding most common indication) randomized to Pipelle vs Explora

curette

no significant difference in subject-reported pain or provider-reported ease of use

Reference - Obstet Gynecol 2011 Mar117(3)636

review of evaluation of the endometrium can be found in Obstet Gynecol 2010 Jul116(1)168

considerations for imaging of endometrial cavity(3)

goals for evaluation of endometrial cavity in women with chronic abnormaluterinebleeding include detection of endometrial

hyperplasia or cancer in selected patients and identification of focal lesions such as polyps and leiomyomas (fibroids) which

might explain bleeding (Kaiser Level C)

if chronic abnormaluterinebleeding continues despite normal and satisfactory endometrial sampling consider ultrasound

saline infusion sonography andor hysteroscopy (Kaiser Level A)

transvaginal ultrasound considered adequate if entire endometrial echo shown in longitudinal and transverse planes through

widest part of endometrial cavity (Kaiser Level C)

no consensus on upper limit of endometrial thickness to be considered normal in premenopausal women (Kaiser Level B)

transvaginal ultrasound considered good screening test but may miss some focal lesions such as polyps (Kaiser Level B)

transvaginal ultrasound sonohysterography and hysteroscopy may be similarly effective in detection of

intrauterine pathology in premenopausal women with abnormaluterinebleeding (level 2 [mid-level] evidence)

based on systematic review with heterogeneity

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Acute severe bleeding

19 prospective cohort studies reviewed including 2917 patients 408 (25) postmenopausal

for detection of any intrauterine pathology statistically significant heterogeneity prevented pooling of likelihood ratios

for detection of submucous fibroids

sonohysterography had pooled likelihood ratio 297 (95 CI 178-496)

hysteroscopy had pooled likelihood ratio 294 (95 CI 134-653)

pooled likelihood ratio for transvaginal ultrasound not calculated because of statistically significant heterogeneity

Reference - Acta Obstet Gynecol Scand 2003 Jun82(6)493 EBSCOhost Full Text

prophylactic vaginal misoprostol may reduce pain in women having outpatient hysteroscopy (level 2 [mid-

level] evidence)

based on randomized trial with allocation concealment not stated

150 women having outpatient hysteroscopy for diagnosis of infertility or abnormaluterinebleeding randomized to cervical

priming with misoprostol 200 mcg vaginally 3 hours before procedure vs no misoprostol

comparing misoprostol vs no misoprostol

mean pain scores (on 0-10 visual analog scale) 326 vs 487 (p lt 0001)

mean procedure time 2 minutes vs 25 minutes (p lt 0001)

misoprostol associated with increased ease of cervical entry and patient acceptability (p le 002 for each)

Reference - Fertil Steril 2011 Oct96(4)962

American Institute of Ultrasound in Medicine (AIUM) guideline on pelvic ultrasound examinations can be found in J Ultrasound

Med 2010 Jan29(1)166

review of evaluation of the endometrium can be found in Obstet Gynecol 2010 Jul116(1)168

Management

indications for hospitalization(1)

orthostatic hypotension

hemoglobin lt 10 gdL

profuse active bleeding

consider blood transfusion if severely anemic(1)

hormonal medication

estrogen

use often recommended but evidence for efficacy is limited(1 2)

IV conjugated equine estrogen may terminate endometrial bleeding in patients with dysfunctional

uterinebleeding (DUB) (level 2 [mid-level] evidence)

based on small randomized trial

34 patients who presented to emergency room with excessive or prolonged uterinebleeding were randomized to

conjugated estrogens (Premarin) 25 mg vs placebo in 5 mL normal saline injected IV over 2 minutes through IV

line running at 75 mLhour

dose repeated (double-blind Premarin or placebo) at 3 hours if bleeding continued

open-label dose of Premarin (regardless of original assignment) at 5 hours if bleeding continued

alternative treatment provided if bleeding continued at 8 hours

comparing estrogen vs placebo

mean duration of bleeding at presentation 141 days (range 1-78) vs 116 days (range 1-90)

bleeding stopped after first injection in 22 vs 36 (not significant)

bleeding stopped after first or second injection in 72 vs 38 (p = 0021 NNT 3)

adverse effects in 39 vs 13 (not significant)

Reference - Obstet Gynecol 1982 Mar59(3)285

DynaMed commentary -- patients had range of bleeding history unclear how many had acute severe bleeding

dose schedules suggested in review article(1)

for inpatient management

conjugated equine estrogens 25 mg in normal saline 50 mL given IV over 20 minutes every 4 hours for 24

hours

at same time start tapered dosing of combination oral contraceptive (ethinyl estradiol 30 mcgnorgestrel 03

mg)

for outpatient management

conjugated equine estrogens 25 mg orally 4 times daily

after acute bleeding stopped start tapered dosing of combination oral contraceptive (ethinyl estradiol 30

mcgnorgestrel 03 mg)

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Irregular menstrual bleeding

tapered dose schedule

1 tablet 4 times daily for 4 days then

1 tablet 3 times daily for 3 days then

1 tablet twice daily for 2 days then

1 tablet once daily for 3 weeks then

1 week off then cycle of oral contraceptives for at least 3 months

oral medroxyprogesterone acetate and combination oral contraceptives appear equally effective in

terminating acute uterinebleeding (level 2 [mid-level] evidence)

based on small randomized trial

40 hemodynamically stable patients with acute uterinebleeding (defined as sufficient to justify immediate medical or

surgical intervention) randomized to

medroxyprogesterone acetate 20 mg orally 3 times daily for 1 week then 20 mg once daily for 3 weeks

monophasic combination oral contraceptive containing norethindrone 1 mg plus ethinyl estradiol 35 mcg 1 tablet 3

times daily for 1 week then 1 tablet once daily for 3 weeks

33 patients (82) evaluated at 14 days

comparing medroxyprogesterone acetate vs combination oral contraceptive

cessation of bleeding achieved in 76 vs 88 (not significant)

median time to bleeding cessation 3 days vs 3 days

emergency surgical procedures avoided in 100 vs 95

no significant differences in incidence of treatment-related nausea and bloating

Reference - Obstet Gynecol 2006 Oct108(4)924

indications for dilatation and curettage or intrauterine Foley bulb placement(1 2)

hemodynamic instability and acute bleeding

lack of response to initial

2 doses of IV estrogen (if inpatient)

4 doses of oral estrogen (if outpatient)

evaluation once patient stabilized(1)

investigation for bleeding disorder (complete blood count platelet count prothrombin time activated partial thromboplastin

time platelet function analysis)

transvaginal ultrasound

medical therapy for irregular menstrual bleeding (presumed anovulatory)

empiric medical management can be started(2)

goal of treatment is to restore natural cycle of endometrial growth and shedding

withdrawal bleeding can be induced by progestin (medroxyprogesterone acetate 5-10 mg daily for 2 weeks every

month)

progestogens given alone (cyclically continuously or nearly continuously) or in combination with estrogens have limited

evidence for management of anovulatory irregular bleeding (Kaiser Level B)(3)

continuing therapy for at least 3 months after stabilization has been suggested for irregular bleeding in nonpregnant

women(1)

no randomized trials found evaluating progestogens alone or in combination with estrogens for irregular or

heavy menstrual bleeding due to anovulation

based on Cochrane review

Reference - Cochrane Database Syst Rev 2012 Sep 12(9)CD001895

metformin and other insulin-sensitizing drugs

role of metformin and other hypoglycemic agents for routine treatment of chronic anovulatory abnormaluterinebleeding

has not been established (Kaiser Level B)(3)

metformin may reduce menstrual abnormalities in women with polycystic ovarian syndrome (PCOS)

metformin may improve menstrual regularity (level 2 [mid-level] evidence) and hormonal markers

(level 3 [lacking direct] evidence) in normal weight normoinsulinemic women with PCOS

based on small randomized trial

28 normal-weight normoinsulinemic women with PCOS randomized to metformin 500 mg twice daily vs

placebo

metformin significantly associated with improved

testosterone levels at 3 and 6 months

17-hydroxyprogesterone levels at 6 months

hirsutism score at 6 months

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reduced ovarian volume at 3 and 6 months

70 in metformin group experienced restoration of menstrual cyclicity

no clinical or hormonal changes with placebo

Reference - Fertil Steril 2010 May 193(7)2303

metformin 850 mg twice daily does not appear to improve menstrual frequency or insulin sensitivity

in obese women with PCOS already making weight loss lifestyle changes (level 2 [mid-level]

evidence)

based on randomized trial with allocation concealment not stated

143 obese oligo-amenorrheic women with PCOS received dietary plan and were randomized to metformin

850 mg twice daily vs placebo for 6 months

metformin significantly reduced waist circumference and free androgen index

no significant difference in

menstrual frequency (both groups improved)

insulin sensitivity

lipid profiles

Reference - Hum Reprod 2006 Jan21(1)80 full-text

metformin may reduce markers of PCOS and menstrual abnormalities

based on small randomized trial

23 women with PCOS randomized to metformin 500 mg vs placebo orally 3 times daily for 6 months

metformin reduced menstrual abnormalities plasma insulin insulin resistance and ovarian hyperandrogenism

no changes in placebo group

warning that ovulation may resume and contraception may be necessary

Reference - J Clin Endocrinol Metab 2000 Jan85(1)139 in Prescribers Letter 2000 Mar7(3)16

metformin associated with higher rate of menses

based on 12-week randomized placebo-controlled trial with 22 patients aged 13-18 years with hyperinsulinemia

and PCOS

Reference - Arch Pediatr Adolesc Med 2006 Mar160(3)241 commentary can be found in Am Fam Physician

2006 Sep 174(5)862

metformin 500-1000 mg twice daily may improve menstrual cyclicity and quality of life in oligo-

amenorrheic women with PCOS (level 2 [mid-level] evidence)

based on cohort study of 64 women (mean age 29 years) with PCOS (all oligoamenorrheic) having

metformin 500-1000 mg twice daily (depending on weight) for 6 months

metformin associated with

normalized menstrual cycle (52 achieved 28-35 cycles)

improved quality of life scores (including domains of vitality social function mental and sexual health)

significant baseline reductions in

insulin resistance

testosterone levels (55 achieved normal levels)

free androgen index levels

body mass index (BMI) (mean decrease 11 kgm )2

no difference in alopecia or hirsutism scores

Reference - Hum Reprod 2006 Jul21(7)1925 full-text

ovulation induction is not indicated (Kaiser Level C)(3)

gonadotropin-releasing hormone (GnRH) agonists may have a role in management of selected women with chronic

anovulatory abnormaluterinebleeding (Kaiser Level B)(3)

lifestyle issues including stress reduction and weight loss might be important in management of abnormaluterinebleeding

associated with anovulatory state (Kaiser Level C)(3)

surgical therapy

surgical therapy for women with chronic dysfunctional uterinebleeding (DUB) is currently reserved for women not interested

in future fertility (Kaiser Level C)(3)

hysterectomy is more effective than endometrial ablation for resolution of symptoms of DUB but has more

adverse perioperative events (level 1 [likely reliable] evidence)

based on randomized trial

237 premenopausal women aged ge 18 years with dysfunctional uterinebleeding randomized to endometrial ablation vs

hysterectomy and followed for up to 5 years

85 were aged lt 45 years

due to funding concerns trial terminated early but gt 80 of women were followed for at least 2 years

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Heavy menstrual bleeding (menorrhagia)

Other management

primary outcome was resolution of the major reason for which women sought treatment (bleeding pain or fatigue)

comparing endometrial ablation vs hysterectomy

879 vs 932 had major problem solved at 1 year

849 vs 944 had major problem solved at 2 years (p = 0026 NNT 11 favoring hysterectomy)

933 vs 951 had major problem solved at 3 years

851 vs 98 had major problem solved at 4 years (p = 0026 NNT 8 favoring hysterectomy)

109 vs 406 had adverse perioperative events (NNT 4 favoring endometrial ablation)

29 (32 of 110 women) with endometrial ablation required reoperation by 48 months

Reference - STOP-DUB trial (Obstet Gynecol 2007 Dec110(6)1279) correction can be found in Obstet Gynecol 2008

Aug112(2 Pt 1)381 commentary can be found in Obstet Gynecol 2008 Apr111(4)992

for patients with abnormaluterinebleeding due to leiomyomas(3)

surgical management of abnormaluterinebleeding due to leiomyomas is determined by size location and number of

myomas (Kaiser Level C)

selected patients with leiomyoma-related abnormaluterinebleeding who do not wish to retain fertility may be considered

for endometrial ablation (Kaiser Level A)

abdominal myomectomy is the preferred procedure for women with abnormaluterinebleeding related to myomas

unsuitable for resectoscopic removal and who wish to retain their uterus (Kaiser Level C)

symptomatic endometrial polyps should be completely removed under hysteroscopic direction (Kaiser Level B)(3)

improvement in quality of life measures should be goal of any interventions (NICE D recommendation)

clarifying values and patient preferences may reduce hysterectomy rates for menorrhagia (level 2 [mid-level] evidence)

medications

levonorgestrel intrauterine system (LNG-IUS) appears effective for heavy menstrual bleeding (level 2 [mid-level] evidence)

and is treatment of choice if (NICE A recommendation)

hormonal treatments are acceptable

at least 12 months use anticipated

combined oral contraceptives is second-line drug treatment option (NICE B recommendation)

either NSAID or tranexamic acid (Lysteda) considered

second-line treatment option if either hormonal or nonhormonal treatments are acceptable (NICE A recommendation)

preferred treatment option if hormonal treatments are not acceptable (NICE D(GPP) recommendation)

tranexamic acid should not be used before LNG-IUS if long-term use is anticipated (NICE A recommendation)

oral progestins (such as norethisterone 15 mg once daily on menstrual cycle days 5-26) or injected long-acting progestins

considered third-line treatment options (NICE A recommendation)

danazol may be effective for heavy menstrual bleeding (level 2 [mid-level] evidence)

surgeryprocedures

surgery reduces menstrual bleeding at 1 year more than medical therapy but levonorgestrel-intrauterine system improves

quality of life as effectively as surgery (level 1 [likely reliable] evidence)

endometrial ablation

preferable to hysterectomy in women with heavy menstrual bleeding alone and uterus le 10 week pregnancy size

(NICE A recommendation)

preprocedure endometrial thinning may improve operative conditions and amenorrhea at 12 months (level 2 [mid-level]

evidence)

referral for consideration of surgery or uterine artery embolization (UAE) as first-line treatment recommended for women

with large fibroids and heavy menstrual bleeding and other significant symptoms such as dysmenorrhea or pressure

symptoms (NICE D(GPP) recommendation)

UAE myomectomy or hysterectomy should all be considered discussed and documented when surgery for fibroid-related

heavy menstrual bleeding is considered necessary (NICE D(GPP) recommendation)

vaginal hysterectomy preferred over abdominal hysterectomy after incorporating individual assessment (NICE A

recommendation)

DampC should not be used as therapeutic treatment (NICE C recommendation)

see Heavy menstrual bleeding for treatment details

assess need for iron therapy

therapy should be individualized

if needed see Iron deficiency anemia in adults

insufficient evidence for evaluation of use of Chinese herbal medication for dysfunctional uterinebleeding (DUB)

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Guidelines

United States guidelines

United Kingdom guidelines

Canadian guidelines

European guidelines

Mexican guidelines

Review articles

based on meta-analysis

all except one trial had poor methodological quality

Reference - Evid Based Complement Alternat Med 2009 Mar6(1)99 full-text

Guidelines and Resources

American College of Obstetricians and Gynecologists (ACOG) guidelines

American College of Obstetricians and Gynecologists (ACOG) Practice Bulletin 128 on diagnosis of abnormaluterinebleeding

in reproductive-aged women can be found in Obstet Gynecol 2012 Jul120(1)197 or at National Guideline Clearinghouse

2013 Feb 1138623 commentary can be found in ACOG News Release 2012 Jun 21

American College of Obstetricians and Gynecologists (ACOG) Committee Opinion 557 on management of acute

abnormaluterinebleeding in nonpregnant reproductive-aged women can be found in Obstet Gynecol 2013 Apr121(4)891

ACOG Practice Bulletin 136 on management of abnormaluterinebleeding associated with ovulatory dysfunction can be

found in Obstet Gynecol 2013 Jul122(1)176 or at National Guideline Clearinghouse 2014 Feb 1747451

ACOG Practice Bulletin 81 on endometrial ablation can be found in Obstet Gynecol 2007 May109(5)1233 reaffirmed 2012

Feb or at National Guideline Clearinghouse 2007 Dec 2410918

ACOG Committee Opinion 349 on menstruation on girls and adolescents can be found in Obstet Gynecol 2006

Nov108(5)1323 reaffirmed 2009 Jun also produced by American Academy of Pediatrics (Pediatrics 2006

Nov118(5)2245)

American College of Radiology (ACR) Appropriateness Criteria for abnormal vaginal bleeding can be found at ACR 2010 PDF or

at National Guideline Clearinghouse 2011 Sep 532629

Society of Gynecologic Surgeons (SGS) clinical practice guideline on abnormaluterinebleeding hysterectomy versus alternative

therapy can be found in J Minim Invasive Gynecol 2012 Jan-Feb19(1)81

American College of RadiologyAmerican College of Obstetricians and GynecologistsAmerican Institute of Ultrasound in Medicine

(ACRACOGAIUM) guideline on performance of sonohysterography can be found in J Ultrasound Med 2012 Jan31(1)165 full-

text or at ACRACOGAIUM 2011 PDF

National Institute for Health and Clinical Excellence (NICE) guideline on

heavy menstrual bleeding can be found in NICE 2007 JanCG44 PDF

fluid-filled thermal balloon and microwave endometrial ablation techniques for heavy menstrual bleeding can be found at

NICE 2004 AprTA78

Royal College of Obstetricians and Gynaecologists (RCOG) guideline on best practice in outpatient hysteroscopy can be found

at RCOG 2011 Mar PDF or at National Guideline Clearinghouse 2012 May 1434905

Society of Obstetricians and Gynaecologists of Canada (SOGC) guideline on abnormaluterinebleeding in pre-menopausal women

can be found at SOGC 2013 May 23 PDF or at National Guideline Clearinghouse 2014 Jan 646416

Society of Obstetricians and Gynaecologists of Canada (SOGC) clinical guideline on female sexual health consensus can be

found at SOGC 2012 PDF or at National Guideline Clearinghouse 2013 Jun 338474

Society of Obstetricians and Gynaecologists of Canada (SOGC) recommendations on asymptomatic endometrial thickening can

be found in J Obstet Gynaecol Can 2010 Oct32(10)990 PDF

Alberta Health Services (AHS) clinical practice guideline on uterine sarcoma can be found at AHS 2011 Aug PDF or at National

Guideline Clearinghouse 2013 Mar 438596

Collegravege National des Gyneacutecologues et Obsteacutetriciens Franccedilais (CNGOF) clinical practice guideline on menorrhagia management of

abnormaluterinebleeding before menopause can be found in Eur J Obstet Gynecol Reprod Biol 2010 Oct152(2)133

Mexican School of Obstetrics and Gynecology (Colegio Mexicano de Especialistas en Ginecologa y Obstetricia) clinical practice

guideline on dysfunctional uterinebleeding can be found in Ginecol Obstet Mex 2009 Sep77(9)S231 EBSCOhost Full Text

[Spanish]

review can be found in Am Fam Physician 2004 Apr 1569(8)1915

review can be found in Postgrad Med 2001 Jan109(1)137

review can be found in Am Fam Physician 1999 Oct 160(5)1371

review of managing unscheduled bleeding in non-pregnant premenopausal women can be found in BMJ 2013 Jun 4346f3251

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ICD-9 codes

ICD-10 codes

General references used

Recommendation grading systems used

AHRQ Comparative Effectiveness Review on primary care management of abnormaluterinebleeding 2013 Mar96 PDF

review of abnormaluterinebleeding in premenopausal women can be found in Am Fam Physician 2012 Jan 185(1)35

EBSCOhost Full Text

reviews of terminology controversy can be found in Fertil Steril 2008 Dec90(6)2269 Curr Opin Obstet Gynecol 2007

Dec19(6)591

review of treatment of dysfunctional uterinebleeding can be found in Maturitas 2004 Mar 1547(3)159

review of health-related quality of life work impairment and health-care costs and utilization in abnormaluterinebleeding can be

found in Value Health 2007 May-Jun10(3)183 EBSCOhost Full Text

Patient Information

handout from American College of Obstetricians and Gynecologists PDF

handout from American Society for Reproductive Medicine PDF

handout from American Academy of Family Physicians or in Spanish

handout on dysfunctional uterinebleeding from TeensHealth or in Spanish

technical information on dysfunctional uterinebleeding from Patient Plus PDF

handout on reasons for problem bleeding from Cleveland Clinic

handout on vaginal bleeding from Mayo Clinic

handout on dysfunctional uterinebleeding questions to discuss with your doctor from Harvard Medical School

ICD-9ICD-10 Codes

6262 excessive or frequent menstruation

6263 puberty bleeding

6264 irregular menstrual cycle

6265 ovulation bleeding

6266 metrorrhagia

6267 postcoital bleeding

6268 other disorders of menstruation and other abnormalbleeding from female genital tract

6269 unspecified disorders of menstruation and other abnormalbleeding from female genital tract

N92 excessive frequent and irregular menstruation

N920 excessive and frequent menstruation with regular cycle

N921 excessive and frequent menstruation with irregular cycle

N922 excessive menstruation at puberty

N923 ovulation bleeding

N924 excessive bleeding in the premenopausal period

N925 other specified irregular menstruation

N926 irregular menstruation unspecified

N93 other abnormaluterine and vaginal bleeding

N930 postcoital and contact bleeding

N938 other specified abnormaluterine and vaginal bleeding

N939 abnormaluterine and vaginal bleeding unspecified

References

1 Ely JW Kennedy CM Clark EC Bowdler NC Abnormaluterinebleeding a management algorithm J Am Board Fam Med

2006 Nov-Dec19(6)590-602 full-text

2 Casablanca Y Management of dysfunctional uterinebleeding Obstet Gynecol Clin North Am 2008 Jun35(2)219-34 viii

3 Amann M Anguino H Bauman RA et al Chronic abnormaluterinebleeding in nongravid women Pasadena (CA) Kaiser

Permanente Southern California National Guideline Clearinghouse 2007 Oct 2910889

4 National Collaborating Centre for Womenrsquos and Childrenrsquos Health Heavy menstrual bleeding National Institute for Health and

Clinical Excellence (NICE) 2007 JanCG44 PDF

Kaiser Permanente Southern California uses American College of Obstetricians and Gynecologists (ACOG) strength of

recommendation classification

grades of recommendation

Level A - based on good and consistent scientific evidence

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DynaMed editorial process

Special acknowledgements

How to cite

Level B - based on limited or inconsistent scientific evidence

Level C - based primarily on consensus and expert opinion

Reference - Kaiser Permanente Southern California guideline on chronic abnormaluterinebleeding in nongravid women

(National Guideline Clearinghouse 2007 Oct 2910889)

National Institute for Health and Clinical Excellence (NICE) grading system for recommendations

Grade A

at least 1 meta-analysis systematic review or randomized controlled trial (RCT) that is rated 1++ and is directly

applicable to target population or

systematic review of RCTs or body of evidence that consists principally of studies rated 1+ is directly applicable to

target population and demonstrates overall consistency of results or

evidence drawn from NICE technology appraisal

Grade B

body of evidence that includes studies rated 2++ is directly applicable to target population and demonstrates overall

consistency of results or

extrapolated evidence from studies rated 1++ or 1+

Grade C

body of evidence that includes studies rated 2++ is directly applicable to target population and demonstrates overall

consistency of results or

extrapolated evidence from studies rated 2++

Grade D

evidence level 3 or 4 or

extrapolated evidence from studies rated 2+ or

formal consensus

Grade D (GPP) - a good practice point (GPP) is a recommendation for best practice based on experience of Guideline

Development Group

levels of evidence for intervention studies

1++ includes high-quality meta-analyses systematic reviews of RCTs or RCTs with very low risk of bias

1+ includes well-conducted meta-analyses systematic reviews of RCTs or RCTs with low risk of bias

1- includes meta-analyses systematic reviews of RCTs or RCTs with high risk of bias

2++ includes high-quality systematic reviews of case-control or cohort studies high-quality case-control or cohort

studies with very low risk of confounding bias or chance and high probability relationship is casual

2+ includes well-conducted case-control or cohort studies with low risk of confounding bias or chance and moderate

probability relationship is casual

2- includes case-control or cohort studies with high risk of confounding bias or chance and significant risk relationship is

not casual

3 includes nonanalytical studies (for example case reports case series)

4 includes expert opinion formal consensus

Reference - NICE guideline on heavy menstrual bleeding (NICE 2007 JanCG44 PDF)

DynaMed topics are created and maintained by the DynaMed Editorial Team

Over 500 journals and evidence-based sources (DynaMed Content Sources) are monitored directly or indirectly using a 7-Step

evidence-based method for systematic literature surveillance DynaMed topics are updated daily as newly discovered best

available evidence is identified

The participating members of the DynaMed Editorial Team have declared that they have no financial or other competing

interests related to this topic

The participating reviewers have declared that they have no financial or other competing interests related to this topic unless

otherwise indicated

McMaster University is a partner that provides support in identifying Practice-Changing DynaMed Updates Over 1000 practicing

physicians from 61 disciplines in 77 countries rate these articles to help you find the most useful new evidence affecting your

practice

F1000 is a partner that provides support in identifying Practice-Changing DynaMed Updates Over 2000 practicing clinicians from

20 disciplines in 60 countries rate these articles to help you find the most useful new evidence affecting your practice

Linda Feng Chang PharmD MPH BCPS (EPC Course Director and Clinical Assistant Professor of Pharmacy University of Illinois

College of Medicine Illinois United States) provides peer review

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copy 2014 EBSCO Industries Inc Todos los derechos reservados

Page 3: Abnormal uterine bleeding - AEEMmedicina-ucr.com/.../2014/04/Abnormal-Uterine-Bleeding-DynaMed.pdf · Abnormal uterine bleeding ... endometrial ablation preferable to hysterectomy

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Gynecologic lesions

Bleeding disorders

History

contraception(1)

oral contraceptives

medroxyprogesterone acetate

intrauterine device (IUD)

anticoagulants(2)

phenytoin(1)

antipsychotics (for example olanzapine risperidone)(1)

tricyclic antidepressants(1)

corticosteroids

tamoxifen(2)

herbal supplements with estrogenic activity(2)

vaginal(2)

genital ulcers

squamous cell carcinoma of vagina

cervical(2)

ulcer

cervical polyp

squamous cell carcinoma of cervix

uterine(2)

leiomyoma (fibroids) most common

endometrial adenocarcinoma endometrial sarcoma

endometrial hyperplasia

endometritis

adenomyomata or diffuse adenomyosis

endometrial polyp

congenital abnormalities

genital trauma(2)

foreign bodies(2)

anticoagulants(2)

von Willebrand disease(2)

other blood dyscrasias(2)

inherited bleeding disorders (most commonly von Willebrand disease) reported in 11-17 women with menorrhagia

cohort of 150 women referred for menorrhagia who had normal pelvic exam

women had measurements of activated partial thromboplastin time factor VIII activity von Willebrand factor antigen

and activity and factor XI

26 (17) had inherited bleeding disorder including

von Willebrand disease in 18

factor XI deficiency in 4

combined von Willebrand disease and factor XI deficiency in 1

combined von Willebrand disease factor XI deficiency and factor X deficiency in 1

hemophilia A carrier in 1

platelet dysfunction in 1

Reference - Lancet 1998 Feb 14351(9101)485 EBSCOhost Full Text

comparing 121 women with menorrhagia vs 123 controls

bleeding disorders diagnosed in 107 vs 32 (p = 002)

von Willebrand disease diagnosed in 8 (66) vs 1 (08) (p = 002)

prevalence of von Willebrand disease 159 white patients vs 14 black patients (p = 001)

Reference - Obstet Gynecol 2001 Apr97(4)630

History and Physical

women with heavy uterinebleeding should have a structured history to screen for inherited systemic disorders of hemostasis

(Kaiser Level A)(3)

patients with positive screening on structured history should be considered for further evaluation including consultation with a

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Physical

Testing overview

hematologist andor testing for von Willebrand disease

positive screen defined as any of

heavy menstrual bleeding since menarche

postpartum hemorrhage

surgery related bleeding

bleeding associated with dental work

2 or more of

family history of bleeding symptoms

bruising 1-2 timesmonth

epistaxis 1-2 timesmonth

frequent gum bleeding

each patient with chronic abnormaluterinebleeding should be assessed for ovulatory function (can be reliably confirmed with a

history of predictable cyclic menses with a cycle length of every 22-35 days) (Kaiser Level C)(3)

determine pattern of bleeding(1)

severe acute bleeding (bleeding requiring gt 1 pad or tampon per hour or vital signs indicating hypovolemia)

irregular bleeding (includes metrorrhagia menometrorrhagia oligomenorrhea prolonged bleeding intermenstrual bleeding

or other irregular pattern)

menorrhagia (heavy but regular cyclic bleeding plus gt 7 days of bleeding or clots or iron deficiency anemia) prolonged

bleeding gt 12 days should be considered irregular regardless of cyclic pattern

ask about

symptoms of anemia (fatigue lightheadedness weakness dyspnea on exertion)(2)

history of weight change(2)

history or symptoms of thyroid disorder(2)

medication use(2)

oral contraceptive

thyroid medications

other hormones

anticoagulants

check for signs of(2)

pregnancy

anemia (pallor tachycardia)

endocrine disorders

hyperandrogenism (acne hirsutism virilization)

hypothyroidism

hyperthyroidism

bleeding disorder (petechiae bruising recurrent or unexplained joint effusion)

abdominal mass (if large uterine fibroid)

gynecological exam for structural lesions(2)

vaginal

genital ulcers

squamous cell carcinoma of vagina

cervical

ulcer

polyp

squamous cell carcinoma of cervix

uterine

leiomyoma (fibroids) most common

endometrial adenocarcinoma endometrial sarcoma

endometritis

adenomyomata or diffuse adenomyosis

polyp

congenital abnormalities

Diagnostic Testing

for all women with chronic abnormaluterinebleeding(3)

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Endometrial sampling

Imaging studies

pregnancy test (urine or blood) should be done (Kaiser Level C)

CBC should be considered (Kaiser Level C)

additional testing guided by patient history(3)

TSH is appropriate in women with suspected or known anovulatory dysfunctional uterinebleeding (DUB) (Kaiser Level C)

endometrial sampling if increased risk of endometrial hyperplasia or neoplasia (Kaiser Level A)

other endocrine tests if indicated

to rule out hyperprolactinemia - prolactin level

to rule out polycystic ovary syndrome or other hyperandrogenic state

17-hydroxyprogesterone

testosterone

dehydroepiandrosterone sulfate

testing for bleeding disorder if bleeding persists despite treatment(3)

platelets

bleeding time

factor VIII

routine transvaginal ultrasonography generally unnecessary for initial visit but should be considered for persisting symptoms and

especially for those who fail initial medical therapy (Kaiser Level C)(3)

indications for further evaluation with ultrasound saline infusion sonography andor hysteroscopy (Kaiser Level A) include(3)

persistent abnormaluterinebleeding despite normal and satisfactory endometrial sampling

irregular thickening of endometrium on ultrasound (suggesting presence of focal lesions)

endometrial cavity cannot be identified in its entirety

if polyps or fibroids involving endometrial cavity suspected

indications for endometrial sampling

endometrial sampling should be performed when there is an increased risk of endometrial hyperplasia or neoplasia (Kaiser

Level A)

women aged gt 40 years (Kaiser Level B)

women aged lt 40 years with additional risk factors (including features suggestive of chronic anovulation and weight greater

than 90 kg) (Kaiser Level B)

patients with a family history of hereditary nonpolyposis colorectal cancer syndrome (Lynch Syndrome) (Kaiser Level B)

sampling approach

outpatient endometrial biopsy with catheter techniques should be considered first line approach (Kaiser Level A)

if endometrial biopsy is indicated and cannot be obtained or is inadequate repeat sampling should be attempted if

necessary with DampC (Kaiser Level C)

Pipelle and Explora curettes associated with similar patient pain ratings in endometrial biopsy (level 2 [mid-

level] evidence)

based on randomized trial with use of means instead of medians for pain analysis

70 women having endometrial biopsy (abnormaluterinebleeding most common indication) randomized to Pipelle vs Explora

curette

no significant difference in subject-reported pain or provider-reported ease of use

Reference - Obstet Gynecol 2011 Mar117(3)636

review of evaluation of the endometrium can be found in Obstet Gynecol 2010 Jul116(1)168

considerations for imaging of endometrial cavity(3)

goals for evaluation of endometrial cavity in women with chronic abnormaluterinebleeding include detection of endometrial

hyperplasia or cancer in selected patients and identification of focal lesions such as polyps and leiomyomas (fibroids) which

might explain bleeding (Kaiser Level C)

if chronic abnormaluterinebleeding continues despite normal and satisfactory endometrial sampling consider ultrasound

saline infusion sonography andor hysteroscopy (Kaiser Level A)

transvaginal ultrasound considered adequate if entire endometrial echo shown in longitudinal and transverse planes through

widest part of endometrial cavity (Kaiser Level C)

no consensus on upper limit of endometrial thickness to be considered normal in premenopausal women (Kaiser Level B)

transvaginal ultrasound considered good screening test but may miss some focal lesions such as polyps (Kaiser Level B)

transvaginal ultrasound sonohysterography and hysteroscopy may be similarly effective in detection of

intrauterine pathology in premenopausal women with abnormaluterinebleeding (level 2 [mid-level] evidence)

based on systematic review with heterogeneity

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Acute severe bleeding

19 prospective cohort studies reviewed including 2917 patients 408 (25) postmenopausal

for detection of any intrauterine pathology statistically significant heterogeneity prevented pooling of likelihood ratios

for detection of submucous fibroids

sonohysterography had pooled likelihood ratio 297 (95 CI 178-496)

hysteroscopy had pooled likelihood ratio 294 (95 CI 134-653)

pooled likelihood ratio for transvaginal ultrasound not calculated because of statistically significant heterogeneity

Reference - Acta Obstet Gynecol Scand 2003 Jun82(6)493 EBSCOhost Full Text

prophylactic vaginal misoprostol may reduce pain in women having outpatient hysteroscopy (level 2 [mid-

level] evidence)

based on randomized trial with allocation concealment not stated

150 women having outpatient hysteroscopy for diagnosis of infertility or abnormaluterinebleeding randomized to cervical

priming with misoprostol 200 mcg vaginally 3 hours before procedure vs no misoprostol

comparing misoprostol vs no misoprostol

mean pain scores (on 0-10 visual analog scale) 326 vs 487 (p lt 0001)

mean procedure time 2 minutes vs 25 minutes (p lt 0001)

misoprostol associated with increased ease of cervical entry and patient acceptability (p le 002 for each)

Reference - Fertil Steril 2011 Oct96(4)962

American Institute of Ultrasound in Medicine (AIUM) guideline on pelvic ultrasound examinations can be found in J Ultrasound

Med 2010 Jan29(1)166

review of evaluation of the endometrium can be found in Obstet Gynecol 2010 Jul116(1)168

Management

indications for hospitalization(1)

orthostatic hypotension

hemoglobin lt 10 gdL

profuse active bleeding

consider blood transfusion if severely anemic(1)

hormonal medication

estrogen

use often recommended but evidence for efficacy is limited(1 2)

IV conjugated equine estrogen may terminate endometrial bleeding in patients with dysfunctional

uterinebleeding (DUB) (level 2 [mid-level] evidence)

based on small randomized trial

34 patients who presented to emergency room with excessive or prolonged uterinebleeding were randomized to

conjugated estrogens (Premarin) 25 mg vs placebo in 5 mL normal saline injected IV over 2 minutes through IV

line running at 75 mLhour

dose repeated (double-blind Premarin or placebo) at 3 hours if bleeding continued

open-label dose of Premarin (regardless of original assignment) at 5 hours if bleeding continued

alternative treatment provided if bleeding continued at 8 hours

comparing estrogen vs placebo

mean duration of bleeding at presentation 141 days (range 1-78) vs 116 days (range 1-90)

bleeding stopped after first injection in 22 vs 36 (not significant)

bleeding stopped after first or second injection in 72 vs 38 (p = 0021 NNT 3)

adverse effects in 39 vs 13 (not significant)

Reference - Obstet Gynecol 1982 Mar59(3)285

DynaMed commentary -- patients had range of bleeding history unclear how many had acute severe bleeding

dose schedules suggested in review article(1)

for inpatient management

conjugated equine estrogens 25 mg in normal saline 50 mL given IV over 20 minutes every 4 hours for 24

hours

at same time start tapered dosing of combination oral contraceptive (ethinyl estradiol 30 mcgnorgestrel 03

mg)

for outpatient management

conjugated equine estrogens 25 mg orally 4 times daily

after acute bleeding stopped start tapered dosing of combination oral contraceptive (ethinyl estradiol 30

mcgnorgestrel 03 mg)

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Irregular menstrual bleeding

tapered dose schedule

1 tablet 4 times daily for 4 days then

1 tablet 3 times daily for 3 days then

1 tablet twice daily for 2 days then

1 tablet once daily for 3 weeks then

1 week off then cycle of oral contraceptives for at least 3 months

oral medroxyprogesterone acetate and combination oral contraceptives appear equally effective in

terminating acute uterinebleeding (level 2 [mid-level] evidence)

based on small randomized trial

40 hemodynamically stable patients with acute uterinebleeding (defined as sufficient to justify immediate medical or

surgical intervention) randomized to

medroxyprogesterone acetate 20 mg orally 3 times daily for 1 week then 20 mg once daily for 3 weeks

monophasic combination oral contraceptive containing norethindrone 1 mg plus ethinyl estradiol 35 mcg 1 tablet 3

times daily for 1 week then 1 tablet once daily for 3 weeks

33 patients (82) evaluated at 14 days

comparing medroxyprogesterone acetate vs combination oral contraceptive

cessation of bleeding achieved in 76 vs 88 (not significant)

median time to bleeding cessation 3 days vs 3 days

emergency surgical procedures avoided in 100 vs 95

no significant differences in incidence of treatment-related nausea and bloating

Reference - Obstet Gynecol 2006 Oct108(4)924

indications for dilatation and curettage or intrauterine Foley bulb placement(1 2)

hemodynamic instability and acute bleeding

lack of response to initial

2 doses of IV estrogen (if inpatient)

4 doses of oral estrogen (if outpatient)

evaluation once patient stabilized(1)

investigation for bleeding disorder (complete blood count platelet count prothrombin time activated partial thromboplastin

time platelet function analysis)

transvaginal ultrasound

medical therapy for irregular menstrual bleeding (presumed anovulatory)

empiric medical management can be started(2)

goal of treatment is to restore natural cycle of endometrial growth and shedding

withdrawal bleeding can be induced by progestin (medroxyprogesterone acetate 5-10 mg daily for 2 weeks every

month)

progestogens given alone (cyclically continuously or nearly continuously) or in combination with estrogens have limited

evidence for management of anovulatory irregular bleeding (Kaiser Level B)(3)

continuing therapy for at least 3 months after stabilization has been suggested for irregular bleeding in nonpregnant

women(1)

no randomized trials found evaluating progestogens alone or in combination with estrogens for irregular or

heavy menstrual bleeding due to anovulation

based on Cochrane review

Reference - Cochrane Database Syst Rev 2012 Sep 12(9)CD001895

metformin and other insulin-sensitizing drugs

role of metformin and other hypoglycemic agents for routine treatment of chronic anovulatory abnormaluterinebleeding

has not been established (Kaiser Level B)(3)

metformin may reduce menstrual abnormalities in women with polycystic ovarian syndrome (PCOS)

metformin may improve menstrual regularity (level 2 [mid-level] evidence) and hormonal markers

(level 3 [lacking direct] evidence) in normal weight normoinsulinemic women with PCOS

based on small randomized trial

28 normal-weight normoinsulinemic women with PCOS randomized to metformin 500 mg twice daily vs

placebo

metformin significantly associated with improved

testosterone levels at 3 and 6 months

17-hydroxyprogesterone levels at 6 months

hirsutism score at 6 months

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reduced ovarian volume at 3 and 6 months

70 in metformin group experienced restoration of menstrual cyclicity

no clinical or hormonal changes with placebo

Reference - Fertil Steril 2010 May 193(7)2303

metformin 850 mg twice daily does not appear to improve menstrual frequency or insulin sensitivity

in obese women with PCOS already making weight loss lifestyle changes (level 2 [mid-level]

evidence)

based on randomized trial with allocation concealment not stated

143 obese oligo-amenorrheic women with PCOS received dietary plan and were randomized to metformin

850 mg twice daily vs placebo for 6 months

metformin significantly reduced waist circumference and free androgen index

no significant difference in

menstrual frequency (both groups improved)

insulin sensitivity

lipid profiles

Reference - Hum Reprod 2006 Jan21(1)80 full-text

metformin may reduce markers of PCOS and menstrual abnormalities

based on small randomized trial

23 women with PCOS randomized to metformin 500 mg vs placebo orally 3 times daily for 6 months

metformin reduced menstrual abnormalities plasma insulin insulin resistance and ovarian hyperandrogenism

no changes in placebo group

warning that ovulation may resume and contraception may be necessary

Reference - J Clin Endocrinol Metab 2000 Jan85(1)139 in Prescribers Letter 2000 Mar7(3)16

metformin associated with higher rate of menses

based on 12-week randomized placebo-controlled trial with 22 patients aged 13-18 years with hyperinsulinemia

and PCOS

Reference - Arch Pediatr Adolesc Med 2006 Mar160(3)241 commentary can be found in Am Fam Physician

2006 Sep 174(5)862

metformin 500-1000 mg twice daily may improve menstrual cyclicity and quality of life in oligo-

amenorrheic women with PCOS (level 2 [mid-level] evidence)

based on cohort study of 64 women (mean age 29 years) with PCOS (all oligoamenorrheic) having

metformin 500-1000 mg twice daily (depending on weight) for 6 months

metformin associated with

normalized menstrual cycle (52 achieved 28-35 cycles)

improved quality of life scores (including domains of vitality social function mental and sexual health)

significant baseline reductions in

insulin resistance

testosterone levels (55 achieved normal levels)

free androgen index levels

body mass index (BMI) (mean decrease 11 kgm )2

no difference in alopecia or hirsutism scores

Reference - Hum Reprod 2006 Jul21(7)1925 full-text

ovulation induction is not indicated (Kaiser Level C)(3)

gonadotropin-releasing hormone (GnRH) agonists may have a role in management of selected women with chronic

anovulatory abnormaluterinebleeding (Kaiser Level B)(3)

lifestyle issues including stress reduction and weight loss might be important in management of abnormaluterinebleeding

associated with anovulatory state (Kaiser Level C)(3)

surgical therapy

surgical therapy for women with chronic dysfunctional uterinebleeding (DUB) is currently reserved for women not interested

in future fertility (Kaiser Level C)(3)

hysterectomy is more effective than endometrial ablation for resolution of symptoms of DUB but has more

adverse perioperative events (level 1 [likely reliable] evidence)

based on randomized trial

237 premenopausal women aged ge 18 years with dysfunctional uterinebleeding randomized to endometrial ablation vs

hysterectomy and followed for up to 5 years

85 were aged lt 45 years

due to funding concerns trial terminated early but gt 80 of women were followed for at least 2 years

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Heavy menstrual bleeding (menorrhagia)

Other management

primary outcome was resolution of the major reason for which women sought treatment (bleeding pain or fatigue)

comparing endometrial ablation vs hysterectomy

879 vs 932 had major problem solved at 1 year

849 vs 944 had major problem solved at 2 years (p = 0026 NNT 11 favoring hysterectomy)

933 vs 951 had major problem solved at 3 years

851 vs 98 had major problem solved at 4 years (p = 0026 NNT 8 favoring hysterectomy)

109 vs 406 had adverse perioperative events (NNT 4 favoring endometrial ablation)

29 (32 of 110 women) with endometrial ablation required reoperation by 48 months

Reference - STOP-DUB trial (Obstet Gynecol 2007 Dec110(6)1279) correction can be found in Obstet Gynecol 2008

Aug112(2 Pt 1)381 commentary can be found in Obstet Gynecol 2008 Apr111(4)992

for patients with abnormaluterinebleeding due to leiomyomas(3)

surgical management of abnormaluterinebleeding due to leiomyomas is determined by size location and number of

myomas (Kaiser Level C)

selected patients with leiomyoma-related abnormaluterinebleeding who do not wish to retain fertility may be considered

for endometrial ablation (Kaiser Level A)

abdominal myomectomy is the preferred procedure for women with abnormaluterinebleeding related to myomas

unsuitable for resectoscopic removal and who wish to retain their uterus (Kaiser Level C)

symptomatic endometrial polyps should be completely removed under hysteroscopic direction (Kaiser Level B)(3)

improvement in quality of life measures should be goal of any interventions (NICE D recommendation)

clarifying values and patient preferences may reduce hysterectomy rates for menorrhagia (level 2 [mid-level] evidence)

medications

levonorgestrel intrauterine system (LNG-IUS) appears effective for heavy menstrual bleeding (level 2 [mid-level] evidence)

and is treatment of choice if (NICE A recommendation)

hormonal treatments are acceptable

at least 12 months use anticipated

combined oral contraceptives is second-line drug treatment option (NICE B recommendation)

either NSAID or tranexamic acid (Lysteda) considered

second-line treatment option if either hormonal or nonhormonal treatments are acceptable (NICE A recommendation)

preferred treatment option if hormonal treatments are not acceptable (NICE D(GPP) recommendation)

tranexamic acid should not be used before LNG-IUS if long-term use is anticipated (NICE A recommendation)

oral progestins (such as norethisterone 15 mg once daily on menstrual cycle days 5-26) or injected long-acting progestins

considered third-line treatment options (NICE A recommendation)

danazol may be effective for heavy menstrual bleeding (level 2 [mid-level] evidence)

surgeryprocedures

surgery reduces menstrual bleeding at 1 year more than medical therapy but levonorgestrel-intrauterine system improves

quality of life as effectively as surgery (level 1 [likely reliable] evidence)

endometrial ablation

preferable to hysterectomy in women with heavy menstrual bleeding alone and uterus le 10 week pregnancy size

(NICE A recommendation)

preprocedure endometrial thinning may improve operative conditions and amenorrhea at 12 months (level 2 [mid-level]

evidence)

referral for consideration of surgery or uterine artery embolization (UAE) as first-line treatment recommended for women

with large fibroids and heavy menstrual bleeding and other significant symptoms such as dysmenorrhea or pressure

symptoms (NICE D(GPP) recommendation)

UAE myomectomy or hysterectomy should all be considered discussed and documented when surgery for fibroid-related

heavy menstrual bleeding is considered necessary (NICE D(GPP) recommendation)

vaginal hysterectomy preferred over abdominal hysterectomy after incorporating individual assessment (NICE A

recommendation)

DampC should not be used as therapeutic treatment (NICE C recommendation)

see Heavy menstrual bleeding for treatment details

assess need for iron therapy

therapy should be individualized

if needed see Iron deficiency anemia in adults

insufficient evidence for evaluation of use of Chinese herbal medication for dysfunctional uterinebleeding (DUB)

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Guidelines

United States guidelines

United Kingdom guidelines

Canadian guidelines

European guidelines

Mexican guidelines

Review articles

based on meta-analysis

all except one trial had poor methodological quality

Reference - Evid Based Complement Alternat Med 2009 Mar6(1)99 full-text

Guidelines and Resources

American College of Obstetricians and Gynecologists (ACOG) guidelines

American College of Obstetricians and Gynecologists (ACOG) Practice Bulletin 128 on diagnosis of abnormaluterinebleeding

in reproductive-aged women can be found in Obstet Gynecol 2012 Jul120(1)197 or at National Guideline Clearinghouse

2013 Feb 1138623 commentary can be found in ACOG News Release 2012 Jun 21

American College of Obstetricians and Gynecologists (ACOG) Committee Opinion 557 on management of acute

abnormaluterinebleeding in nonpregnant reproductive-aged women can be found in Obstet Gynecol 2013 Apr121(4)891

ACOG Practice Bulletin 136 on management of abnormaluterinebleeding associated with ovulatory dysfunction can be

found in Obstet Gynecol 2013 Jul122(1)176 or at National Guideline Clearinghouse 2014 Feb 1747451

ACOG Practice Bulletin 81 on endometrial ablation can be found in Obstet Gynecol 2007 May109(5)1233 reaffirmed 2012

Feb or at National Guideline Clearinghouse 2007 Dec 2410918

ACOG Committee Opinion 349 on menstruation on girls and adolescents can be found in Obstet Gynecol 2006

Nov108(5)1323 reaffirmed 2009 Jun also produced by American Academy of Pediatrics (Pediatrics 2006

Nov118(5)2245)

American College of Radiology (ACR) Appropriateness Criteria for abnormal vaginal bleeding can be found at ACR 2010 PDF or

at National Guideline Clearinghouse 2011 Sep 532629

Society of Gynecologic Surgeons (SGS) clinical practice guideline on abnormaluterinebleeding hysterectomy versus alternative

therapy can be found in J Minim Invasive Gynecol 2012 Jan-Feb19(1)81

American College of RadiologyAmerican College of Obstetricians and GynecologistsAmerican Institute of Ultrasound in Medicine

(ACRACOGAIUM) guideline on performance of sonohysterography can be found in J Ultrasound Med 2012 Jan31(1)165 full-

text or at ACRACOGAIUM 2011 PDF

National Institute for Health and Clinical Excellence (NICE) guideline on

heavy menstrual bleeding can be found in NICE 2007 JanCG44 PDF

fluid-filled thermal balloon and microwave endometrial ablation techniques for heavy menstrual bleeding can be found at

NICE 2004 AprTA78

Royal College of Obstetricians and Gynaecologists (RCOG) guideline on best practice in outpatient hysteroscopy can be found

at RCOG 2011 Mar PDF or at National Guideline Clearinghouse 2012 May 1434905

Society of Obstetricians and Gynaecologists of Canada (SOGC) guideline on abnormaluterinebleeding in pre-menopausal women

can be found at SOGC 2013 May 23 PDF or at National Guideline Clearinghouse 2014 Jan 646416

Society of Obstetricians and Gynaecologists of Canada (SOGC) clinical guideline on female sexual health consensus can be

found at SOGC 2012 PDF or at National Guideline Clearinghouse 2013 Jun 338474

Society of Obstetricians and Gynaecologists of Canada (SOGC) recommendations on asymptomatic endometrial thickening can

be found in J Obstet Gynaecol Can 2010 Oct32(10)990 PDF

Alberta Health Services (AHS) clinical practice guideline on uterine sarcoma can be found at AHS 2011 Aug PDF or at National

Guideline Clearinghouse 2013 Mar 438596

Collegravege National des Gyneacutecologues et Obsteacutetriciens Franccedilais (CNGOF) clinical practice guideline on menorrhagia management of

abnormaluterinebleeding before menopause can be found in Eur J Obstet Gynecol Reprod Biol 2010 Oct152(2)133

Mexican School of Obstetrics and Gynecology (Colegio Mexicano de Especialistas en Ginecologa y Obstetricia) clinical practice

guideline on dysfunctional uterinebleeding can be found in Ginecol Obstet Mex 2009 Sep77(9)S231 EBSCOhost Full Text

[Spanish]

review can be found in Am Fam Physician 2004 Apr 1569(8)1915

review can be found in Postgrad Med 2001 Jan109(1)137

review can be found in Am Fam Physician 1999 Oct 160(5)1371

review of managing unscheduled bleeding in non-pregnant premenopausal women can be found in BMJ 2013 Jun 4346f3251

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ICD-9 codes

ICD-10 codes

General references used

Recommendation grading systems used

AHRQ Comparative Effectiveness Review on primary care management of abnormaluterinebleeding 2013 Mar96 PDF

review of abnormaluterinebleeding in premenopausal women can be found in Am Fam Physician 2012 Jan 185(1)35

EBSCOhost Full Text

reviews of terminology controversy can be found in Fertil Steril 2008 Dec90(6)2269 Curr Opin Obstet Gynecol 2007

Dec19(6)591

review of treatment of dysfunctional uterinebleeding can be found in Maturitas 2004 Mar 1547(3)159

review of health-related quality of life work impairment and health-care costs and utilization in abnormaluterinebleeding can be

found in Value Health 2007 May-Jun10(3)183 EBSCOhost Full Text

Patient Information

handout from American College of Obstetricians and Gynecologists PDF

handout from American Society for Reproductive Medicine PDF

handout from American Academy of Family Physicians or in Spanish

handout on dysfunctional uterinebleeding from TeensHealth or in Spanish

technical information on dysfunctional uterinebleeding from Patient Plus PDF

handout on reasons for problem bleeding from Cleveland Clinic

handout on vaginal bleeding from Mayo Clinic

handout on dysfunctional uterinebleeding questions to discuss with your doctor from Harvard Medical School

ICD-9ICD-10 Codes

6262 excessive or frequent menstruation

6263 puberty bleeding

6264 irregular menstrual cycle

6265 ovulation bleeding

6266 metrorrhagia

6267 postcoital bleeding

6268 other disorders of menstruation and other abnormalbleeding from female genital tract

6269 unspecified disorders of menstruation and other abnormalbleeding from female genital tract

N92 excessive frequent and irregular menstruation

N920 excessive and frequent menstruation with regular cycle

N921 excessive and frequent menstruation with irregular cycle

N922 excessive menstruation at puberty

N923 ovulation bleeding

N924 excessive bleeding in the premenopausal period

N925 other specified irregular menstruation

N926 irregular menstruation unspecified

N93 other abnormaluterine and vaginal bleeding

N930 postcoital and contact bleeding

N938 other specified abnormaluterine and vaginal bleeding

N939 abnormaluterine and vaginal bleeding unspecified

References

1 Ely JW Kennedy CM Clark EC Bowdler NC Abnormaluterinebleeding a management algorithm J Am Board Fam Med

2006 Nov-Dec19(6)590-602 full-text

2 Casablanca Y Management of dysfunctional uterinebleeding Obstet Gynecol Clin North Am 2008 Jun35(2)219-34 viii

3 Amann M Anguino H Bauman RA et al Chronic abnormaluterinebleeding in nongravid women Pasadena (CA) Kaiser

Permanente Southern California National Guideline Clearinghouse 2007 Oct 2910889

4 National Collaborating Centre for Womenrsquos and Childrenrsquos Health Heavy menstrual bleeding National Institute for Health and

Clinical Excellence (NICE) 2007 JanCG44 PDF

Kaiser Permanente Southern California uses American College of Obstetricians and Gynecologists (ACOG) strength of

recommendation classification

grades of recommendation

Level A - based on good and consistent scientific evidence

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DynaMed editorial process

Special acknowledgements

How to cite

Level B - based on limited or inconsistent scientific evidence

Level C - based primarily on consensus and expert opinion

Reference - Kaiser Permanente Southern California guideline on chronic abnormaluterinebleeding in nongravid women

(National Guideline Clearinghouse 2007 Oct 2910889)

National Institute for Health and Clinical Excellence (NICE) grading system for recommendations

Grade A

at least 1 meta-analysis systematic review or randomized controlled trial (RCT) that is rated 1++ and is directly

applicable to target population or

systematic review of RCTs or body of evidence that consists principally of studies rated 1+ is directly applicable to

target population and demonstrates overall consistency of results or

evidence drawn from NICE technology appraisal

Grade B

body of evidence that includes studies rated 2++ is directly applicable to target population and demonstrates overall

consistency of results or

extrapolated evidence from studies rated 1++ or 1+

Grade C

body of evidence that includes studies rated 2++ is directly applicable to target population and demonstrates overall

consistency of results or

extrapolated evidence from studies rated 2++

Grade D

evidence level 3 or 4 or

extrapolated evidence from studies rated 2+ or

formal consensus

Grade D (GPP) - a good practice point (GPP) is a recommendation for best practice based on experience of Guideline

Development Group

levels of evidence for intervention studies

1++ includes high-quality meta-analyses systematic reviews of RCTs or RCTs with very low risk of bias

1+ includes well-conducted meta-analyses systematic reviews of RCTs or RCTs with low risk of bias

1- includes meta-analyses systematic reviews of RCTs or RCTs with high risk of bias

2++ includes high-quality systematic reviews of case-control or cohort studies high-quality case-control or cohort

studies with very low risk of confounding bias or chance and high probability relationship is casual

2+ includes well-conducted case-control or cohort studies with low risk of confounding bias or chance and moderate

probability relationship is casual

2- includes case-control or cohort studies with high risk of confounding bias or chance and significant risk relationship is

not casual

3 includes nonanalytical studies (for example case reports case series)

4 includes expert opinion formal consensus

Reference - NICE guideline on heavy menstrual bleeding (NICE 2007 JanCG44 PDF)

DynaMed topics are created and maintained by the DynaMed Editorial Team

Over 500 journals and evidence-based sources (DynaMed Content Sources) are monitored directly or indirectly using a 7-Step

evidence-based method for systematic literature surveillance DynaMed topics are updated daily as newly discovered best

available evidence is identified

The participating members of the DynaMed Editorial Team have declared that they have no financial or other competing

interests related to this topic

The participating reviewers have declared that they have no financial or other competing interests related to this topic unless

otherwise indicated

McMaster University is a partner that provides support in identifying Practice-Changing DynaMed Updates Over 1000 practicing

physicians from 61 disciplines in 77 countries rate these articles to help you find the most useful new evidence affecting your

practice

F1000 is a partner that provides support in identifying Practice-Changing DynaMed Updates Over 2000 practicing clinicians from

20 disciplines in 60 countries rate these articles to help you find the most useful new evidence affecting your practice

Linda Feng Chang PharmD MPH BCPS (EPC Course Director and Clinical Assistant Professor of Pharmacy University of Illinois

College of Medicine Illinois United States) provides peer review

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copy 2014 EBSCO Industries Inc Todos los derechos reservados

Page 4: Abnormal uterine bleeding - AEEMmedicina-ucr.com/.../2014/04/Abnormal-Uterine-Bleeding-DynaMed.pdf · Abnormal uterine bleeding ... endometrial ablation preferable to hysterectomy

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Physical

Testing overview

hematologist andor testing for von Willebrand disease

positive screen defined as any of

heavy menstrual bleeding since menarche

postpartum hemorrhage

surgery related bleeding

bleeding associated with dental work

2 or more of

family history of bleeding symptoms

bruising 1-2 timesmonth

epistaxis 1-2 timesmonth

frequent gum bleeding

each patient with chronic abnormaluterinebleeding should be assessed for ovulatory function (can be reliably confirmed with a

history of predictable cyclic menses with a cycle length of every 22-35 days) (Kaiser Level C)(3)

determine pattern of bleeding(1)

severe acute bleeding (bleeding requiring gt 1 pad or tampon per hour or vital signs indicating hypovolemia)

irregular bleeding (includes metrorrhagia menometrorrhagia oligomenorrhea prolonged bleeding intermenstrual bleeding

or other irregular pattern)

menorrhagia (heavy but regular cyclic bleeding plus gt 7 days of bleeding or clots or iron deficiency anemia) prolonged

bleeding gt 12 days should be considered irregular regardless of cyclic pattern

ask about

symptoms of anemia (fatigue lightheadedness weakness dyspnea on exertion)(2)

history of weight change(2)

history or symptoms of thyroid disorder(2)

medication use(2)

oral contraceptive

thyroid medications

other hormones

anticoagulants

check for signs of(2)

pregnancy

anemia (pallor tachycardia)

endocrine disorders

hyperandrogenism (acne hirsutism virilization)

hypothyroidism

hyperthyroidism

bleeding disorder (petechiae bruising recurrent or unexplained joint effusion)

abdominal mass (if large uterine fibroid)

gynecological exam for structural lesions(2)

vaginal

genital ulcers

squamous cell carcinoma of vagina

cervical

ulcer

polyp

squamous cell carcinoma of cervix

uterine

leiomyoma (fibroids) most common

endometrial adenocarcinoma endometrial sarcoma

endometritis

adenomyomata or diffuse adenomyosis

polyp

congenital abnormalities

Diagnostic Testing

for all women with chronic abnormaluterinebleeding(3)

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Endometrial sampling

Imaging studies

pregnancy test (urine or blood) should be done (Kaiser Level C)

CBC should be considered (Kaiser Level C)

additional testing guided by patient history(3)

TSH is appropriate in women with suspected or known anovulatory dysfunctional uterinebleeding (DUB) (Kaiser Level C)

endometrial sampling if increased risk of endometrial hyperplasia or neoplasia (Kaiser Level A)

other endocrine tests if indicated

to rule out hyperprolactinemia - prolactin level

to rule out polycystic ovary syndrome or other hyperandrogenic state

17-hydroxyprogesterone

testosterone

dehydroepiandrosterone sulfate

testing for bleeding disorder if bleeding persists despite treatment(3)

platelets

bleeding time

factor VIII

routine transvaginal ultrasonography generally unnecessary for initial visit but should be considered for persisting symptoms and

especially for those who fail initial medical therapy (Kaiser Level C)(3)

indications for further evaluation with ultrasound saline infusion sonography andor hysteroscopy (Kaiser Level A) include(3)

persistent abnormaluterinebleeding despite normal and satisfactory endometrial sampling

irregular thickening of endometrium on ultrasound (suggesting presence of focal lesions)

endometrial cavity cannot be identified in its entirety

if polyps or fibroids involving endometrial cavity suspected

indications for endometrial sampling

endometrial sampling should be performed when there is an increased risk of endometrial hyperplasia or neoplasia (Kaiser

Level A)

women aged gt 40 years (Kaiser Level B)

women aged lt 40 years with additional risk factors (including features suggestive of chronic anovulation and weight greater

than 90 kg) (Kaiser Level B)

patients with a family history of hereditary nonpolyposis colorectal cancer syndrome (Lynch Syndrome) (Kaiser Level B)

sampling approach

outpatient endometrial biopsy with catheter techniques should be considered first line approach (Kaiser Level A)

if endometrial biopsy is indicated and cannot be obtained or is inadequate repeat sampling should be attempted if

necessary with DampC (Kaiser Level C)

Pipelle and Explora curettes associated with similar patient pain ratings in endometrial biopsy (level 2 [mid-

level] evidence)

based on randomized trial with use of means instead of medians for pain analysis

70 women having endometrial biopsy (abnormaluterinebleeding most common indication) randomized to Pipelle vs Explora

curette

no significant difference in subject-reported pain or provider-reported ease of use

Reference - Obstet Gynecol 2011 Mar117(3)636

review of evaluation of the endometrium can be found in Obstet Gynecol 2010 Jul116(1)168

considerations for imaging of endometrial cavity(3)

goals for evaluation of endometrial cavity in women with chronic abnormaluterinebleeding include detection of endometrial

hyperplasia or cancer in selected patients and identification of focal lesions such as polyps and leiomyomas (fibroids) which

might explain bleeding (Kaiser Level C)

if chronic abnormaluterinebleeding continues despite normal and satisfactory endometrial sampling consider ultrasound

saline infusion sonography andor hysteroscopy (Kaiser Level A)

transvaginal ultrasound considered adequate if entire endometrial echo shown in longitudinal and transverse planes through

widest part of endometrial cavity (Kaiser Level C)

no consensus on upper limit of endometrial thickness to be considered normal in premenopausal women (Kaiser Level B)

transvaginal ultrasound considered good screening test but may miss some focal lesions such as polyps (Kaiser Level B)

transvaginal ultrasound sonohysterography and hysteroscopy may be similarly effective in detection of

intrauterine pathology in premenopausal women with abnormaluterinebleeding (level 2 [mid-level] evidence)

based on systematic review with heterogeneity

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Acute severe bleeding

19 prospective cohort studies reviewed including 2917 patients 408 (25) postmenopausal

for detection of any intrauterine pathology statistically significant heterogeneity prevented pooling of likelihood ratios

for detection of submucous fibroids

sonohysterography had pooled likelihood ratio 297 (95 CI 178-496)

hysteroscopy had pooled likelihood ratio 294 (95 CI 134-653)

pooled likelihood ratio for transvaginal ultrasound not calculated because of statistically significant heterogeneity

Reference - Acta Obstet Gynecol Scand 2003 Jun82(6)493 EBSCOhost Full Text

prophylactic vaginal misoprostol may reduce pain in women having outpatient hysteroscopy (level 2 [mid-

level] evidence)

based on randomized trial with allocation concealment not stated

150 women having outpatient hysteroscopy for diagnosis of infertility or abnormaluterinebleeding randomized to cervical

priming with misoprostol 200 mcg vaginally 3 hours before procedure vs no misoprostol

comparing misoprostol vs no misoprostol

mean pain scores (on 0-10 visual analog scale) 326 vs 487 (p lt 0001)

mean procedure time 2 minutes vs 25 minutes (p lt 0001)

misoprostol associated with increased ease of cervical entry and patient acceptability (p le 002 for each)

Reference - Fertil Steril 2011 Oct96(4)962

American Institute of Ultrasound in Medicine (AIUM) guideline on pelvic ultrasound examinations can be found in J Ultrasound

Med 2010 Jan29(1)166

review of evaluation of the endometrium can be found in Obstet Gynecol 2010 Jul116(1)168

Management

indications for hospitalization(1)

orthostatic hypotension

hemoglobin lt 10 gdL

profuse active bleeding

consider blood transfusion if severely anemic(1)

hormonal medication

estrogen

use often recommended but evidence for efficacy is limited(1 2)

IV conjugated equine estrogen may terminate endometrial bleeding in patients with dysfunctional

uterinebleeding (DUB) (level 2 [mid-level] evidence)

based on small randomized trial

34 patients who presented to emergency room with excessive or prolonged uterinebleeding were randomized to

conjugated estrogens (Premarin) 25 mg vs placebo in 5 mL normal saline injected IV over 2 minutes through IV

line running at 75 mLhour

dose repeated (double-blind Premarin or placebo) at 3 hours if bleeding continued

open-label dose of Premarin (regardless of original assignment) at 5 hours if bleeding continued

alternative treatment provided if bleeding continued at 8 hours

comparing estrogen vs placebo

mean duration of bleeding at presentation 141 days (range 1-78) vs 116 days (range 1-90)

bleeding stopped after first injection in 22 vs 36 (not significant)

bleeding stopped after first or second injection in 72 vs 38 (p = 0021 NNT 3)

adverse effects in 39 vs 13 (not significant)

Reference - Obstet Gynecol 1982 Mar59(3)285

DynaMed commentary -- patients had range of bleeding history unclear how many had acute severe bleeding

dose schedules suggested in review article(1)

for inpatient management

conjugated equine estrogens 25 mg in normal saline 50 mL given IV over 20 minutes every 4 hours for 24

hours

at same time start tapered dosing of combination oral contraceptive (ethinyl estradiol 30 mcgnorgestrel 03

mg)

for outpatient management

conjugated equine estrogens 25 mg orally 4 times daily

after acute bleeding stopped start tapered dosing of combination oral contraceptive (ethinyl estradiol 30

mcgnorgestrel 03 mg)

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Irregular menstrual bleeding

tapered dose schedule

1 tablet 4 times daily for 4 days then

1 tablet 3 times daily for 3 days then

1 tablet twice daily for 2 days then

1 tablet once daily for 3 weeks then

1 week off then cycle of oral contraceptives for at least 3 months

oral medroxyprogesterone acetate and combination oral contraceptives appear equally effective in

terminating acute uterinebleeding (level 2 [mid-level] evidence)

based on small randomized trial

40 hemodynamically stable patients with acute uterinebleeding (defined as sufficient to justify immediate medical or

surgical intervention) randomized to

medroxyprogesterone acetate 20 mg orally 3 times daily for 1 week then 20 mg once daily for 3 weeks

monophasic combination oral contraceptive containing norethindrone 1 mg plus ethinyl estradiol 35 mcg 1 tablet 3

times daily for 1 week then 1 tablet once daily for 3 weeks

33 patients (82) evaluated at 14 days

comparing medroxyprogesterone acetate vs combination oral contraceptive

cessation of bleeding achieved in 76 vs 88 (not significant)

median time to bleeding cessation 3 days vs 3 days

emergency surgical procedures avoided in 100 vs 95

no significant differences in incidence of treatment-related nausea and bloating

Reference - Obstet Gynecol 2006 Oct108(4)924

indications for dilatation and curettage or intrauterine Foley bulb placement(1 2)

hemodynamic instability and acute bleeding

lack of response to initial

2 doses of IV estrogen (if inpatient)

4 doses of oral estrogen (if outpatient)

evaluation once patient stabilized(1)

investigation for bleeding disorder (complete blood count platelet count prothrombin time activated partial thromboplastin

time platelet function analysis)

transvaginal ultrasound

medical therapy for irregular menstrual bleeding (presumed anovulatory)

empiric medical management can be started(2)

goal of treatment is to restore natural cycle of endometrial growth and shedding

withdrawal bleeding can be induced by progestin (medroxyprogesterone acetate 5-10 mg daily for 2 weeks every

month)

progestogens given alone (cyclically continuously or nearly continuously) or in combination with estrogens have limited

evidence for management of anovulatory irregular bleeding (Kaiser Level B)(3)

continuing therapy for at least 3 months after stabilization has been suggested for irregular bleeding in nonpregnant

women(1)

no randomized trials found evaluating progestogens alone or in combination with estrogens for irregular or

heavy menstrual bleeding due to anovulation

based on Cochrane review

Reference - Cochrane Database Syst Rev 2012 Sep 12(9)CD001895

metformin and other insulin-sensitizing drugs

role of metformin and other hypoglycemic agents for routine treatment of chronic anovulatory abnormaluterinebleeding

has not been established (Kaiser Level B)(3)

metformin may reduce menstrual abnormalities in women with polycystic ovarian syndrome (PCOS)

metformin may improve menstrual regularity (level 2 [mid-level] evidence) and hormonal markers

(level 3 [lacking direct] evidence) in normal weight normoinsulinemic women with PCOS

based on small randomized trial

28 normal-weight normoinsulinemic women with PCOS randomized to metformin 500 mg twice daily vs

placebo

metformin significantly associated with improved

testosterone levels at 3 and 6 months

17-hydroxyprogesterone levels at 6 months

hirsutism score at 6 months

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reduced ovarian volume at 3 and 6 months

70 in metformin group experienced restoration of menstrual cyclicity

no clinical or hormonal changes with placebo

Reference - Fertil Steril 2010 May 193(7)2303

metformin 850 mg twice daily does not appear to improve menstrual frequency or insulin sensitivity

in obese women with PCOS already making weight loss lifestyle changes (level 2 [mid-level]

evidence)

based on randomized trial with allocation concealment not stated

143 obese oligo-amenorrheic women with PCOS received dietary plan and were randomized to metformin

850 mg twice daily vs placebo for 6 months

metformin significantly reduced waist circumference and free androgen index

no significant difference in

menstrual frequency (both groups improved)

insulin sensitivity

lipid profiles

Reference - Hum Reprod 2006 Jan21(1)80 full-text

metformin may reduce markers of PCOS and menstrual abnormalities

based on small randomized trial

23 women with PCOS randomized to metformin 500 mg vs placebo orally 3 times daily for 6 months

metformin reduced menstrual abnormalities plasma insulin insulin resistance and ovarian hyperandrogenism

no changes in placebo group

warning that ovulation may resume and contraception may be necessary

Reference - J Clin Endocrinol Metab 2000 Jan85(1)139 in Prescribers Letter 2000 Mar7(3)16

metformin associated with higher rate of menses

based on 12-week randomized placebo-controlled trial with 22 patients aged 13-18 years with hyperinsulinemia

and PCOS

Reference - Arch Pediatr Adolesc Med 2006 Mar160(3)241 commentary can be found in Am Fam Physician

2006 Sep 174(5)862

metformin 500-1000 mg twice daily may improve menstrual cyclicity and quality of life in oligo-

amenorrheic women with PCOS (level 2 [mid-level] evidence)

based on cohort study of 64 women (mean age 29 years) with PCOS (all oligoamenorrheic) having

metformin 500-1000 mg twice daily (depending on weight) for 6 months

metformin associated with

normalized menstrual cycle (52 achieved 28-35 cycles)

improved quality of life scores (including domains of vitality social function mental and sexual health)

significant baseline reductions in

insulin resistance

testosterone levels (55 achieved normal levels)

free androgen index levels

body mass index (BMI) (mean decrease 11 kgm )2

no difference in alopecia or hirsutism scores

Reference - Hum Reprod 2006 Jul21(7)1925 full-text

ovulation induction is not indicated (Kaiser Level C)(3)

gonadotropin-releasing hormone (GnRH) agonists may have a role in management of selected women with chronic

anovulatory abnormaluterinebleeding (Kaiser Level B)(3)

lifestyle issues including stress reduction and weight loss might be important in management of abnormaluterinebleeding

associated with anovulatory state (Kaiser Level C)(3)

surgical therapy

surgical therapy for women with chronic dysfunctional uterinebleeding (DUB) is currently reserved for women not interested

in future fertility (Kaiser Level C)(3)

hysterectomy is more effective than endometrial ablation for resolution of symptoms of DUB but has more

adverse perioperative events (level 1 [likely reliable] evidence)

based on randomized trial

237 premenopausal women aged ge 18 years with dysfunctional uterinebleeding randomized to endometrial ablation vs

hysterectomy and followed for up to 5 years

85 were aged lt 45 years

due to funding concerns trial terminated early but gt 80 of women were followed for at least 2 years

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Heavy menstrual bleeding (menorrhagia)

Other management

primary outcome was resolution of the major reason for which women sought treatment (bleeding pain or fatigue)

comparing endometrial ablation vs hysterectomy

879 vs 932 had major problem solved at 1 year

849 vs 944 had major problem solved at 2 years (p = 0026 NNT 11 favoring hysterectomy)

933 vs 951 had major problem solved at 3 years

851 vs 98 had major problem solved at 4 years (p = 0026 NNT 8 favoring hysterectomy)

109 vs 406 had adverse perioperative events (NNT 4 favoring endometrial ablation)

29 (32 of 110 women) with endometrial ablation required reoperation by 48 months

Reference - STOP-DUB trial (Obstet Gynecol 2007 Dec110(6)1279) correction can be found in Obstet Gynecol 2008

Aug112(2 Pt 1)381 commentary can be found in Obstet Gynecol 2008 Apr111(4)992

for patients with abnormaluterinebleeding due to leiomyomas(3)

surgical management of abnormaluterinebleeding due to leiomyomas is determined by size location and number of

myomas (Kaiser Level C)

selected patients with leiomyoma-related abnormaluterinebleeding who do not wish to retain fertility may be considered

for endometrial ablation (Kaiser Level A)

abdominal myomectomy is the preferred procedure for women with abnormaluterinebleeding related to myomas

unsuitable for resectoscopic removal and who wish to retain their uterus (Kaiser Level C)

symptomatic endometrial polyps should be completely removed under hysteroscopic direction (Kaiser Level B)(3)

improvement in quality of life measures should be goal of any interventions (NICE D recommendation)

clarifying values and patient preferences may reduce hysterectomy rates for menorrhagia (level 2 [mid-level] evidence)

medications

levonorgestrel intrauterine system (LNG-IUS) appears effective for heavy menstrual bleeding (level 2 [mid-level] evidence)

and is treatment of choice if (NICE A recommendation)

hormonal treatments are acceptable

at least 12 months use anticipated

combined oral contraceptives is second-line drug treatment option (NICE B recommendation)

either NSAID or tranexamic acid (Lysteda) considered

second-line treatment option if either hormonal or nonhormonal treatments are acceptable (NICE A recommendation)

preferred treatment option if hormonal treatments are not acceptable (NICE D(GPP) recommendation)

tranexamic acid should not be used before LNG-IUS if long-term use is anticipated (NICE A recommendation)

oral progestins (such as norethisterone 15 mg once daily on menstrual cycle days 5-26) or injected long-acting progestins

considered third-line treatment options (NICE A recommendation)

danazol may be effective for heavy menstrual bleeding (level 2 [mid-level] evidence)

surgeryprocedures

surgery reduces menstrual bleeding at 1 year more than medical therapy but levonorgestrel-intrauterine system improves

quality of life as effectively as surgery (level 1 [likely reliable] evidence)

endometrial ablation

preferable to hysterectomy in women with heavy menstrual bleeding alone and uterus le 10 week pregnancy size

(NICE A recommendation)

preprocedure endometrial thinning may improve operative conditions and amenorrhea at 12 months (level 2 [mid-level]

evidence)

referral for consideration of surgery or uterine artery embolization (UAE) as first-line treatment recommended for women

with large fibroids and heavy menstrual bleeding and other significant symptoms such as dysmenorrhea or pressure

symptoms (NICE D(GPP) recommendation)

UAE myomectomy or hysterectomy should all be considered discussed and documented when surgery for fibroid-related

heavy menstrual bleeding is considered necessary (NICE D(GPP) recommendation)

vaginal hysterectomy preferred over abdominal hysterectomy after incorporating individual assessment (NICE A

recommendation)

DampC should not be used as therapeutic treatment (NICE C recommendation)

see Heavy menstrual bleeding for treatment details

assess need for iron therapy

therapy should be individualized

if needed see Iron deficiency anemia in adults

insufficient evidence for evaluation of use of Chinese herbal medication for dysfunctional uterinebleeding (DUB)

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Guidelines

United States guidelines

United Kingdom guidelines

Canadian guidelines

European guidelines

Mexican guidelines

Review articles

based on meta-analysis

all except one trial had poor methodological quality

Reference - Evid Based Complement Alternat Med 2009 Mar6(1)99 full-text

Guidelines and Resources

American College of Obstetricians and Gynecologists (ACOG) guidelines

American College of Obstetricians and Gynecologists (ACOG) Practice Bulletin 128 on diagnosis of abnormaluterinebleeding

in reproductive-aged women can be found in Obstet Gynecol 2012 Jul120(1)197 or at National Guideline Clearinghouse

2013 Feb 1138623 commentary can be found in ACOG News Release 2012 Jun 21

American College of Obstetricians and Gynecologists (ACOG) Committee Opinion 557 on management of acute

abnormaluterinebleeding in nonpregnant reproductive-aged women can be found in Obstet Gynecol 2013 Apr121(4)891

ACOG Practice Bulletin 136 on management of abnormaluterinebleeding associated with ovulatory dysfunction can be

found in Obstet Gynecol 2013 Jul122(1)176 or at National Guideline Clearinghouse 2014 Feb 1747451

ACOG Practice Bulletin 81 on endometrial ablation can be found in Obstet Gynecol 2007 May109(5)1233 reaffirmed 2012

Feb or at National Guideline Clearinghouse 2007 Dec 2410918

ACOG Committee Opinion 349 on menstruation on girls and adolescents can be found in Obstet Gynecol 2006

Nov108(5)1323 reaffirmed 2009 Jun also produced by American Academy of Pediatrics (Pediatrics 2006

Nov118(5)2245)

American College of Radiology (ACR) Appropriateness Criteria for abnormal vaginal bleeding can be found at ACR 2010 PDF or

at National Guideline Clearinghouse 2011 Sep 532629

Society of Gynecologic Surgeons (SGS) clinical practice guideline on abnormaluterinebleeding hysterectomy versus alternative

therapy can be found in J Minim Invasive Gynecol 2012 Jan-Feb19(1)81

American College of RadiologyAmerican College of Obstetricians and GynecologistsAmerican Institute of Ultrasound in Medicine

(ACRACOGAIUM) guideline on performance of sonohysterography can be found in J Ultrasound Med 2012 Jan31(1)165 full-

text or at ACRACOGAIUM 2011 PDF

National Institute for Health and Clinical Excellence (NICE) guideline on

heavy menstrual bleeding can be found in NICE 2007 JanCG44 PDF

fluid-filled thermal balloon and microwave endometrial ablation techniques for heavy menstrual bleeding can be found at

NICE 2004 AprTA78

Royal College of Obstetricians and Gynaecologists (RCOG) guideline on best practice in outpatient hysteroscopy can be found

at RCOG 2011 Mar PDF or at National Guideline Clearinghouse 2012 May 1434905

Society of Obstetricians and Gynaecologists of Canada (SOGC) guideline on abnormaluterinebleeding in pre-menopausal women

can be found at SOGC 2013 May 23 PDF or at National Guideline Clearinghouse 2014 Jan 646416

Society of Obstetricians and Gynaecologists of Canada (SOGC) clinical guideline on female sexual health consensus can be

found at SOGC 2012 PDF or at National Guideline Clearinghouse 2013 Jun 338474

Society of Obstetricians and Gynaecologists of Canada (SOGC) recommendations on asymptomatic endometrial thickening can

be found in J Obstet Gynaecol Can 2010 Oct32(10)990 PDF

Alberta Health Services (AHS) clinical practice guideline on uterine sarcoma can be found at AHS 2011 Aug PDF or at National

Guideline Clearinghouse 2013 Mar 438596

Collegravege National des Gyneacutecologues et Obsteacutetriciens Franccedilais (CNGOF) clinical practice guideline on menorrhagia management of

abnormaluterinebleeding before menopause can be found in Eur J Obstet Gynecol Reprod Biol 2010 Oct152(2)133

Mexican School of Obstetrics and Gynecology (Colegio Mexicano de Especialistas en Ginecologa y Obstetricia) clinical practice

guideline on dysfunctional uterinebleeding can be found in Ginecol Obstet Mex 2009 Sep77(9)S231 EBSCOhost Full Text

[Spanish]

review can be found in Am Fam Physician 2004 Apr 1569(8)1915

review can be found in Postgrad Med 2001 Jan109(1)137

review can be found in Am Fam Physician 1999 Oct 160(5)1371

review of managing unscheduled bleeding in non-pregnant premenopausal women can be found in BMJ 2013 Jun 4346f3251

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ICD-9 codes

ICD-10 codes

General references used

Recommendation grading systems used

AHRQ Comparative Effectiveness Review on primary care management of abnormaluterinebleeding 2013 Mar96 PDF

review of abnormaluterinebleeding in premenopausal women can be found in Am Fam Physician 2012 Jan 185(1)35

EBSCOhost Full Text

reviews of terminology controversy can be found in Fertil Steril 2008 Dec90(6)2269 Curr Opin Obstet Gynecol 2007

Dec19(6)591

review of treatment of dysfunctional uterinebleeding can be found in Maturitas 2004 Mar 1547(3)159

review of health-related quality of life work impairment and health-care costs and utilization in abnormaluterinebleeding can be

found in Value Health 2007 May-Jun10(3)183 EBSCOhost Full Text

Patient Information

handout from American College of Obstetricians and Gynecologists PDF

handout from American Society for Reproductive Medicine PDF

handout from American Academy of Family Physicians or in Spanish

handout on dysfunctional uterinebleeding from TeensHealth or in Spanish

technical information on dysfunctional uterinebleeding from Patient Plus PDF

handout on reasons for problem bleeding from Cleveland Clinic

handout on vaginal bleeding from Mayo Clinic

handout on dysfunctional uterinebleeding questions to discuss with your doctor from Harvard Medical School

ICD-9ICD-10 Codes

6262 excessive or frequent menstruation

6263 puberty bleeding

6264 irregular menstrual cycle

6265 ovulation bleeding

6266 metrorrhagia

6267 postcoital bleeding

6268 other disorders of menstruation and other abnormalbleeding from female genital tract

6269 unspecified disorders of menstruation and other abnormalbleeding from female genital tract

N92 excessive frequent and irregular menstruation

N920 excessive and frequent menstruation with regular cycle

N921 excessive and frequent menstruation with irregular cycle

N922 excessive menstruation at puberty

N923 ovulation bleeding

N924 excessive bleeding in the premenopausal period

N925 other specified irregular menstruation

N926 irregular menstruation unspecified

N93 other abnormaluterine and vaginal bleeding

N930 postcoital and contact bleeding

N938 other specified abnormaluterine and vaginal bleeding

N939 abnormaluterine and vaginal bleeding unspecified

References

1 Ely JW Kennedy CM Clark EC Bowdler NC Abnormaluterinebleeding a management algorithm J Am Board Fam Med

2006 Nov-Dec19(6)590-602 full-text

2 Casablanca Y Management of dysfunctional uterinebleeding Obstet Gynecol Clin North Am 2008 Jun35(2)219-34 viii

3 Amann M Anguino H Bauman RA et al Chronic abnormaluterinebleeding in nongravid women Pasadena (CA) Kaiser

Permanente Southern California National Guideline Clearinghouse 2007 Oct 2910889

4 National Collaborating Centre for Womenrsquos and Childrenrsquos Health Heavy menstrual bleeding National Institute for Health and

Clinical Excellence (NICE) 2007 JanCG44 PDF

Kaiser Permanente Southern California uses American College of Obstetricians and Gynecologists (ACOG) strength of

recommendation classification

grades of recommendation

Level A - based on good and consistent scientific evidence

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DynaMed editorial process

Special acknowledgements

How to cite

Level B - based on limited or inconsistent scientific evidence

Level C - based primarily on consensus and expert opinion

Reference - Kaiser Permanente Southern California guideline on chronic abnormaluterinebleeding in nongravid women

(National Guideline Clearinghouse 2007 Oct 2910889)

National Institute for Health and Clinical Excellence (NICE) grading system for recommendations

Grade A

at least 1 meta-analysis systematic review or randomized controlled trial (RCT) that is rated 1++ and is directly

applicable to target population or

systematic review of RCTs or body of evidence that consists principally of studies rated 1+ is directly applicable to

target population and demonstrates overall consistency of results or

evidence drawn from NICE technology appraisal

Grade B

body of evidence that includes studies rated 2++ is directly applicable to target population and demonstrates overall

consistency of results or

extrapolated evidence from studies rated 1++ or 1+

Grade C

body of evidence that includes studies rated 2++ is directly applicable to target population and demonstrates overall

consistency of results or

extrapolated evidence from studies rated 2++

Grade D

evidence level 3 or 4 or

extrapolated evidence from studies rated 2+ or

formal consensus

Grade D (GPP) - a good practice point (GPP) is a recommendation for best practice based on experience of Guideline

Development Group

levels of evidence for intervention studies

1++ includes high-quality meta-analyses systematic reviews of RCTs or RCTs with very low risk of bias

1+ includes well-conducted meta-analyses systematic reviews of RCTs or RCTs with low risk of bias

1- includes meta-analyses systematic reviews of RCTs or RCTs with high risk of bias

2++ includes high-quality systematic reviews of case-control or cohort studies high-quality case-control or cohort

studies with very low risk of confounding bias or chance and high probability relationship is casual

2+ includes well-conducted case-control or cohort studies with low risk of confounding bias or chance and moderate

probability relationship is casual

2- includes case-control or cohort studies with high risk of confounding bias or chance and significant risk relationship is

not casual

3 includes nonanalytical studies (for example case reports case series)

4 includes expert opinion formal consensus

Reference - NICE guideline on heavy menstrual bleeding (NICE 2007 JanCG44 PDF)

DynaMed topics are created and maintained by the DynaMed Editorial Team

Over 500 journals and evidence-based sources (DynaMed Content Sources) are monitored directly or indirectly using a 7-Step

evidence-based method for systematic literature surveillance DynaMed topics are updated daily as newly discovered best

available evidence is identified

The participating members of the DynaMed Editorial Team have declared that they have no financial or other competing

interests related to this topic

The participating reviewers have declared that they have no financial or other competing interests related to this topic unless

otherwise indicated

McMaster University is a partner that provides support in identifying Practice-Changing DynaMed Updates Over 1000 practicing

physicians from 61 disciplines in 77 countries rate these articles to help you find the most useful new evidence affecting your

practice

F1000 is a partner that provides support in identifying Practice-Changing DynaMed Updates Over 2000 practicing clinicians from

20 disciplines in 60 countries rate these articles to help you find the most useful new evidence affecting your practice

Linda Feng Chang PharmD MPH BCPS (EPC Course Director and Clinical Assistant Professor of Pharmacy University of Illinois

College of Medicine Illinois United States) provides peer review

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Estaacute viendo un resumen de DynaMed El uso de DynaMed indica la aceptacioacuten de las DynaMed Condiciones de uso Las limitaciones de

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copy 2014 EBSCO Industries Inc Todos los derechos reservados

Page 5: Abnormal uterine bleeding - AEEMmedicina-ucr.com/.../2014/04/Abnormal-Uterine-Bleeding-DynaMed.pdf · Abnormal uterine bleeding ... endometrial ablation preferable to hysterectomy

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Endometrial sampling

Imaging studies

pregnancy test (urine or blood) should be done (Kaiser Level C)

CBC should be considered (Kaiser Level C)

additional testing guided by patient history(3)

TSH is appropriate in women with suspected or known anovulatory dysfunctional uterinebleeding (DUB) (Kaiser Level C)

endometrial sampling if increased risk of endometrial hyperplasia or neoplasia (Kaiser Level A)

other endocrine tests if indicated

to rule out hyperprolactinemia - prolactin level

to rule out polycystic ovary syndrome or other hyperandrogenic state

17-hydroxyprogesterone

testosterone

dehydroepiandrosterone sulfate

testing for bleeding disorder if bleeding persists despite treatment(3)

platelets

bleeding time

factor VIII

routine transvaginal ultrasonography generally unnecessary for initial visit but should be considered for persisting symptoms and

especially for those who fail initial medical therapy (Kaiser Level C)(3)

indications for further evaluation with ultrasound saline infusion sonography andor hysteroscopy (Kaiser Level A) include(3)

persistent abnormaluterinebleeding despite normal and satisfactory endometrial sampling

irregular thickening of endometrium on ultrasound (suggesting presence of focal lesions)

endometrial cavity cannot be identified in its entirety

if polyps or fibroids involving endometrial cavity suspected

indications for endometrial sampling

endometrial sampling should be performed when there is an increased risk of endometrial hyperplasia or neoplasia (Kaiser

Level A)

women aged gt 40 years (Kaiser Level B)

women aged lt 40 years with additional risk factors (including features suggestive of chronic anovulation and weight greater

than 90 kg) (Kaiser Level B)

patients with a family history of hereditary nonpolyposis colorectal cancer syndrome (Lynch Syndrome) (Kaiser Level B)

sampling approach

outpatient endometrial biopsy with catheter techniques should be considered first line approach (Kaiser Level A)

if endometrial biopsy is indicated and cannot be obtained or is inadequate repeat sampling should be attempted if

necessary with DampC (Kaiser Level C)

Pipelle and Explora curettes associated with similar patient pain ratings in endometrial biopsy (level 2 [mid-

level] evidence)

based on randomized trial with use of means instead of medians for pain analysis

70 women having endometrial biopsy (abnormaluterinebleeding most common indication) randomized to Pipelle vs Explora

curette

no significant difference in subject-reported pain or provider-reported ease of use

Reference - Obstet Gynecol 2011 Mar117(3)636

review of evaluation of the endometrium can be found in Obstet Gynecol 2010 Jul116(1)168

considerations for imaging of endometrial cavity(3)

goals for evaluation of endometrial cavity in women with chronic abnormaluterinebleeding include detection of endometrial

hyperplasia or cancer in selected patients and identification of focal lesions such as polyps and leiomyomas (fibroids) which

might explain bleeding (Kaiser Level C)

if chronic abnormaluterinebleeding continues despite normal and satisfactory endometrial sampling consider ultrasound

saline infusion sonography andor hysteroscopy (Kaiser Level A)

transvaginal ultrasound considered adequate if entire endometrial echo shown in longitudinal and transverse planes through

widest part of endometrial cavity (Kaiser Level C)

no consensus on upper limit of endometrial thickness to be considered normal in premenopausal women (Kaiser Level B)

transvaginal ultrasound considered good screening test but may miss some focal lesions such as polyps (Kaiser Level B)

transvaginal ultrasound sonohysterography and hysteroscopy may be similarly effective in detection of

intrauterine pathology in premenopausal women with abnormaluterinebleeding (level 2 [mid-level] evidence)

based on systematic review with heterogeneity

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Acute severe bleeding

19 prospective cohort studies reviewed including 2917 patients 408 (25) postmenopausal

for detection of any intrauterine pathology statistically significant heterogeneity prevented pooling of likelihood ratios

for detection of submucous fibroids

sonohysterography had pooled likelihood ratio 297 (95 CI 178-496)

hysteroscopy had pooled likelihood ratio 294 (95 CI 134-653)

pooled likelihood ratio for transvaginal ultrasound not calculated because of statistically significant heterogeneity

Reference - Acta Obstet Gynecol Scand 2003 Jun82(6)493 EBSCOhost Full Text

prophylactic vaginal misoprostol may reduce pain in women having outpatient hysteroscopy (level 2 [mid-

level] evidence)

based on randomized trial with allocation concealment not stated

150 women having outpatient hysteroscopy for diagnosis of infertility or abnormaluterinebleeding randomized to cervical

priming with misoprostol 200 mcg vaginally 3 hours before procedure vs no misoprostol

comparing misoprostol vs no misoprostol

mean pain scores (on 0-10 visual analog scale) 326 vs 487 (p lt 0001)

mean procedure time 2 minutes vs 25 minutes (p lt 0001)

misoprostol associated with increased ease of cervical entry and patient acceptability (p le 002 for each)

Reference - Fertil Steril 2011 Oct96(4)962

American Institute of Ultrasound in Medicine (AIUM) guideline on pelvic ultrasound examinations can be found in J Ultrasound

Med 2010 Jan29(1)166

review of evaluation of the endometrium can be found in Obstet Gynecol 2010 Jul116(1)168

Management

indications for hospitalization(1)

orthostatic hypotension

hemoglobin lt 10 gdL

profuse active bleeding

consider blood transfusion if severely anemic(1)

hormonal medication

estrogen

use often recommended but evidence for efficacy is limited(1 2)

IV conjugated equine estrogen may terminate endometrial bleeding in patients with dysfunctional

uterinebleeding (DUB) (level 2 [mid-level] evidence)

based on small randomized trial

34 patients who presented to emergency room with excessive or prolonged uterinebleeding were randomized to

conjugated estrogens (Premarin) 25 mg vs placebo in 5 mL normal saline injected IV over 2 minutes through IV

line running at 75 mLhour

dose repeated (double-blind Premarin or placebo) at 3 hours if bleeding continued

open-label dose of Premarin (regardless of original assignment) at 5 hours if bleeding continued

alternative treatment provided if bleeding continued at 8 hours

comparing estrogen vs placebo

mean duration of bleeding at presentation 141 days (range 1-78) vs 116 days (range 1-90)

bleeding stopped after first injection in 22 vs 36 (not significant)

bleeding stopped after first or second injection in 72 vs 38 (p = 0021 NNT 3)

adverse effects in 39 vs 13 (not significant)

Reference - Obstet Gynecol 1982 Mar59(3)285

DynaMed commentary -- patients had range of bleeding history unclear how many had acute severe bleeding

dose schedules suggested in review article(1)

for inpatient management

conjugated equine estrogens 25 mg in normal saline 50 mL given IV over 20 minutes every 4 hours for 24

hours

at same time start tapered dosing of combination oral contraceptive (ethinyl estradiol 30 mcgnorgestrel 03

mg)

for outpatient management

conjugated equine estrogens 25 mg orally 4 times daily

after acute bleeding stopped start tapered dosing of combination oral contraceptive (ethinyl estradiol 30

mcgnorgestrel 03 mg)

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Irregular menstrual bleeding

tapered dose schedule

1 tablet 4 times daily for 4 days then

1 tablet 3 times daily for 3 days then

1 tablet twice daily for 2 days then

1 tablet once daily for 3 weeks then

1 week off then cycle of oral contraceptives for at least 3 months

oral medroxyprogesterone acetate and combination oral contraceptives appear equally effective in

terminating acute uterinebleeding (level 2 [mid-level] evidence)

based on small randomized trial

40 hemodynamically stable patients with acute uterinebleeding (defined as sufficient to justify immediate medical or

surgical intervention) randomized to

medroxyprogesterone acetate 20 mg orally 3 times daily for 1 week then 20 mg once daily for 3 weeks

monophasic combination oral contraceptive containing norethindrone 1 mg plus ethinyl estradiol 35 mcg 1 tablet 3

times daily for 1 week then 1 tablet once daily for 3 weeks

33 patients (82) evaluated at 14 days

comparing medroxyprogesterone acetate vs combination oral contraceptive

cessation of bleeding achieved in 76 vs 88 (not significant)

median time to bleeding cessation 3 days vs 3 days

emergency surgical procedures avoided in 100 vs 95

no significant differences in incidence of treatment-related nausea and bloating

Reference - Obstet Gynecol 2006 Oct108(4)924

indications for dilatation and curettage or intrauterine Foley bulb placement(1 2)

hemodynamic instability and acute bleeding

lack of response to initial

2 doses of IV estrogen (if inpatient)

4 doses of oral estrogen (if outpatient)

evaluation once patient stabilized(1)

investigation for bleeding disorder (complete blood count platelet count prothrombin time activated partial thromboplastin

time platelet function analysis)

transvaginal ultrasound

medical therapy for irregular menstrual bleeding (presumed anovulatory)

empiric medical management can be started(2)

goal of treatment is to restore natural cycle of endometrial growth and shedding

withdrawal bleeding can be induced by progestin (medroxyprogesterone acetate 5-10 mg daily for 2 weeks every

month)

progestogens given alone (cyclically continuously or nearly continuously) or in combination with estrogens have limited

evidence for management of anovulatory irregular bleeding (Kaiser Level B)(3)

continuing therapy for at least 3 months after stabilization has been suggested for irregular bleeding in nonpregnant

women(1)

no randomized trials found evaluating progestogens alone or in combination with estrogens for irregular or

heavy menstrual bleeding due to anovulation

based on Cochrane review

Reference - Cochrane Database Syst Rev 2012 Sep 12(9)CD001895

metformin and other insulin-sensitizing drugs

role of metformin and other hypoglycemic agents for routine treatment of chronic anovulatory abnormaluterinebleeding

has not been established (Kaiser Level B)(3)

metformin may reduce menstrual abnormalities in women with polycystic ovarian syndrome (PCOS)

metformin may improve menstrual regularity (level 2 [mid-level] evidence) and hormonal markers

(level 3 [lacking direct] evidence) in normal weight normoinsulinemic women with PCOS

based on small randomized trial

28 normal-weight normoinsulinemic women with PCOS randomized to metformin 500 mg twice daily vs

placebo

metformin significantly associated with improved

testosterone levels at 3 and 6 months

17-hydroxyprogesterone levels at 6 months

hirsutism score at 6 months

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reduced ovarian volume at 3 and 6 months

70 in metformin group experienced restoration of menstrual cyclicity

no clinical or hormonal changes with placebo

Reference - Fertil Steril 2010 May 193(7)2303

metformin 850 mg twice daily does not appear to improve menstrual frequency or insulin sensitivity

in obese women with PCOS already making weight loss lifestyle changes (level 2 [mid-level]

evidence)

based on randomized trial with allocation concealment not stated

143 obese oligo-amenorrheic women with PCOS received dietary plan and were randomized to metformin

850 mg twice daily vs placebo for 6 months

metformin significantly reduced waist circumference and free androgen index

no significant difference in

menstrual frequency (both groups improved)

insulin sensitivity

lipid profiles

Reference - Hum Reprod 2006 Jan21(1)80 full-text

metformin may reduce markers of PCOS and menstrual abnormalities

based on small randomized trial

23 women with PCOS randomized to metformin 500 mg vs placebo orally 3 times daily for 6 months

metformin reduced menstrual abnormalities plasma insulin insulin resistance and ovarian hyperandrogenism

no changes in placebo group

warning that ovulation may resume and contraception may be necessary

Reference - J Clin Endocrinol Metab 2000 Jan85(1)139 in Prescribers Letter 2000 Mar7(3)16

metformin associated with higher rate of menses

based on 12-week randomized placebo-controlled trial with 22 patients aged 13-18 years with hyperinsulinemia

and PCOS

Reference - Arch Pediatr Adolesc Med 2006 Mar160(3)241 commentary can be found in Am Fam Physician

2006 Sep 174(5)862

metformin 500-1000 mg twice daily may improve menstrual cyclicity and quality of life in oligo-

amenorrheic women with PCOS (level 2 [mid-level] evidence)

based on cohort study of 64 women (mean age 29 years) with PCOS (all oligoamenorrheic) having

metformin 500-1000 mg twice daily (depending on weight) for 6 months

metformin associated with

normalized menstrual cycle (52 achieved 28-35 cycles)

improved quality of life scores (including domains of vitality social function mental and sexual health)

significant baseline reductions in

insulin resistance

testosterone levels (55 achieved normal levels)

free androgen index levels

body mass index (BMI) (mean decrease 11 kgm )2

no difference in alopecia or hirsutism scores

Reference - Hum Reprod 2006 Jul21(7)1925 full-text

ovulation induction is not indicated (Kaiser Level C)(3)

gonadotropin-releasing hormone (GnRH) agonists may have a role in management of selected women with chronic

anovulatory abnormaluterinebleeding (Kaiser Level B)(3)

lifestyle issues including stress reduction and weight loss might be important in management of abnormaluterinebleeding

associated with anovulatory state (Kaiser Level C)(3)

surgical therapy

surgical therapy for women with chronic dysfunctional uterinebleeding (DUB) is currently reserved for women not interested

in future fertility (Kaiser Level C)(3)

hysterectomy is more effective than endometrial ablation for resolution of symptoms of DUB but has more

adverse perioperative events (level 1 [likely reliable] evidence)

based on randomized trial

237 premenopausal women aged ge 18 years with dysfunctional uterinebleeding randomized to endometrial ablation vs

hysterectomy and followed for up to 5 years

85 were aged lt 45 years

due to funding concerns trial terminated early but gt 80 of women were followed for at least 2 years

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Heavy menstrual bleeding (menorrhagia)

Other management

primary outcome was resolution of the major reason for which women sought treatment (bleeding pain or fatigue)

comparing endometrial ablation vs hysterectomy

879 vs 932 had major problem solved at 1 year

849 vs 944 had major problem solved at 2 years (p = 0026 NNT 11 favoring hysterectomy)

933 vs 951 had major problem solved at 3 years

851 vs 98 had major problem solved at 4 years (p = 0026 NNT 8 favoring hysterectomy)

109 vs 406 had adverse perioperative events (NNT 4 favoring endometrial ablation)

29 (32 of 110 women) with endometrial ablation required reoperation by 48 months

Reference - STOP-DUB trial (Obstet Gynecol 2007 Dec110(6)1279) correction can be found in Obstet Gynecol 2008

Aug112(2 Pt 1)381 commentary can be found in Obstet Gynecol 2008 Apr111(4)992

for patients with abnormaluterinebleeding due to leiomyomas(3)

surgical management of abnormaluterinebleeding due to leiomyomas is determined by size location and number of

myomas (Kaiser Level C)

selected patients with leiomyoma-related abnormaluterinebleeding who do not wish to retain fertility may be considered

for endometrial ablation (Kaiser Level A)

abdominal myomectomy is the preferred procedure for women with abnormaluterinebleeding related to myomas

unsuitable for resectoscopic removal and who wish to retain their uterus (Kaiser Level C)

symptomatic endometrial polyps should be completely removed under hysteroscopic direction (Kaiser Level B)(3)

improvement in quality of life measures should be goal of any interventions (NICE D recommendation)

clarifying values and patient preferences may reduce hysterectomy rates for menorrhagia (level 2 [mid-level] evidence)

medications

levonorgestrel intrauterine system (LNG-IUS) appears effective for heavy menstrual bleeding (level 2 [mid-level] evidence)

and is treatment of choice if (NICE A recommendation)

hormonal treatments are acceptable

at least 12 months use anticipated

combined oral contraceptives is second-line drug treatment option (NICE B recommendation)

either NSAID or tranexamic acid (Lysteda) considered

second-line treatment option if either hormonal or nonhormonal treatments are acceptable (NICE A recommendation)

preferred treatment option if hormonal treatments are not acceptable (NICE D(GPP) recommendation)

tranexamic acid should not be used before LNG-IUS if long-term use is anticipated (NICE A recommendation)

oral progestins (such as norethisterone 15 mg once daily on menstrual cycle days 5-26) or injected long-acting progestins

considered third-line treatment options (NICE A recommendation)

danazol may be effective for heavy menstrual bleeding (level 2 [mid-level] evidence)

surgeryprocedures

surgery reduces menstrual bleeding at 1 year more than medical therapy but levonorgestrel-intrauterine system improves

quality of life as effectively as surgery (level 1 [likely reliable] evidence)

endometrial ablation

preferable to hysterectomy in women with heavy menstrual bleeding alone and uterus le 10 week pregnancy size

(NICE A recommendation)

preprocedure endometrial thinning may improve operative conditions and amenorrhea at 12 months (level 2 [mid-level]

evidence)

referral for consideration of surgery or uterine artery embolization (UAE) as first-line treatment recommended for women

with large fibroids and heavy menstrual bleeding and other significant symptoms such as dysmenorrhea or pressure

symptoms (NICE D(GPP) recommendation)

UAE myomectomy or hysterectomy should all be considered discussed and documented when surgery for fibroid-related

heavy menstrual bleeding is considered necessary (NICE D(GPP) recommendation)

vaginal hysterectomy preferred over abdominal hysterectomy after incorporating individual assessment (NICE A

recommendation)

DampC should not be used as therapeutic treatment (NICE C recommendation)

see Heavy menstrual bleeding for treatment details

assess need for iron therapy

therapy should be individualized

if needed see Iron deficiency anemia in adults

insufficient evidence for evaluation of use of Chinese herbal medication for dysfunctional uterinebleeding (DUB)

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Guidelines

United States guidelines

United Kingdom guidelines

Canadian guidelines

European guidelines

Mexican guidelines

Review articles

based on meta-analysis

all except one trial had poor methodological quality

Reference - Evid Based Complement Alternat Med 2009 Mar6(1)99 full-text

Guidelines and Resources

American College of Obstetricians and Gynecologists (ACOG) guidelines

American College of Obstetricians and Gynecologists (ACOG) Practice Bulletin 128 on diagnosis of abnormaluterinebleeding

in reproductive-aged women can be found in Obstet Gynecol 2012 Jul120(1)197 or at National Guideline Clearinghouse

2013 Feb 1138623 commentary can be found in ACOG News Release 2012 Jun 21

American College of Obstetricians and Gynecologists (ACOG) Committee Opinion 557 on management of acute

abnormaluterinebleeding in nonpregnant reproductive-aged women can be found in Obstet Gynecol 2013 Apr121(4)891

ACOG Practice Bulletin 136 on management of abnormaluterinebleeding associated with ovulatory dysfunction can be

found in Obstet Gynecol 2013 Jul122(1)176 or at National Guideline Clearinghouse 2014 Feb 1747451

ACOG Practice Bulletin 81 on endometrial ablation can be found in Obstet Gynecol 2007 May109(5)1233 reaffirmed 2012

Feb or at National Guideline Clearinghouse 2007 Dec 2410918

ACOG Committee Opinion 349 on menstruation on girls and adolescents can be found in Obstet Gynecol 2006

Nov108(5)1323 reaffirmed 2009 Jun also produced by American Academy of Pediatrics (Pediatrics 2006

Nov118(5)2245)

American College of Radiology (ACR) Appropriateness Criteria for abnormal vaginal bleeding can be found at ACR 2010 PDF or

at National Guideline Clearinghouse 2011 Sep 532629

Society of Gynecologic Surgeons (SGS) clinical practice guideline on abnormaluterinebleeding hysterectomy versus alternative

therapy can be found in J Minim Invasive Gynecol 2012 Jan-Feb19(1)81

American College of RadiologyAmerican College of Obstetricians and GynecologistsAmerican Institute of Ultrasound in Medicine

(ACRACOGAIUM) guideline on performance of sonohysterography can be found in J Ultrasound Med 2012 Jan31(1)165 full-

text or at ACRACOGAIUM 2011 PDF

National Institute for Health and Clinical Excellence (NICE) guideline on

heavy menstrual bleeding can be found in NICE 2007 JanCG44 PDF

fluid-filled thermal balloon and microwave endometrial ablation techniques for heavy menstrual bleeding can be found at

NICE 2004 AprTA78

Royal College of Obstetricians and Gynaecologists (RCOG) guideline on best practice in outpatient hysteroscopy can be found

at RCOG 2011 Mar PDF or at National Guideline Clearinghouse 2012 May 1434905

Society of Obstetricians and Gynaecologists of Canada (SOGC) guideline on abnormaluterinebleeding in pre-menopausal women

can be found at SOGC 2013 May 23 PDF or at National Guideline Clearinghouse 2014 Jan 646416

Society of Obstetricians and Gynaecologists of Canada (SOGC) clinical guideline on female sexual health consensus can be

found at SOGC 2012 PDF or at National Guideline Clearinghouse 2013 Jun 338474

Society of Obstetricians and Gynaecologists of Canada (SOGC) recommendations on asymptomatic endometrial thickening can

be found in J Obstet Gynaecol Can 2010 Oct32(10)990 PDF

Alberta Health Services (AHS) clinical practice guideline on uterine sarcoma can be found at AHS 2011 Aug PDF or at National

Guideline Clearinghouse 2013 Mar 438596

Collegravege National des Gyneacutecologues et Obsteacutetriciens Franccedilais (CNGOF) clinical practice guideline on menorrhagia management of

abnormaluterinebleeding before menopause can be found in Eur J Obstet Gynecol Reprod Biol 2010 Oct152(2)133

Mexican School of Obstetrics and Gynecology (Colegio Mexicano de Especialistas en Ginecologa y Obstetricia) clinical practice

guideline on dysfunctional uterinebleeding can be found in Ginecol Obstet Mex 2009 Sep77(9)S231 EBSCOhost Full Text

[Spanish]

review can be found in Am Fam Physician 2004 Apr 1569(8)1915

review can be found in Postgrad Med 2001 Jan109(1)137

review can be found in Am Fam Physician 1999 Oct 160(5)1371

review of managing unscheduled bleeding in non-pregnant premenopausal women can be found in BMJ 2013 Jun 4346f3251

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ICD-9 codes

ICD-10 codes

General references used

Recommendation grading systems used

AHRQ Comparative Effectiveness Review on primary care management of abnormaluterinebleeding 2013 Mar96 PDF

review of abnormaluterinebleeding in premenopausal women can be found in Am Fam Physician 2012 Jan 185(1)35

EBSCOhost Full Text

reviews of terminology controversy can be found in Fertil Steril 2008 Dec90(6)2269 Curr Opin Obstet Gynecol 2007

Dec19(6)591

review of treatment of dysfunctional uterinebleeding can be found in Maturitas 2004 Mar 1547(3)159

review of health-related quality of life work impairment and health-care costs and utilization in abnormaluterinebleeding can be

found in Value Health 2007 May-Jun10(3)183 EBSCOhost Full Text

Patient Information

handout from American College of Obstetricians and Gynecologists PDF

handout from American Society for Reproductive Medicine PDF

handout from American Academy of Family Physicians or in Spanish

handout on dysfunctional uterinebleeding from TeensHealth or in Spanish

technical information on dysfunctional uterinebleeding from Patient Plus PDF

handout on reasons for problem bleeding from Cleveland Clinic

handout on vaginal bleeding from Mayo Clinic

handout on dysfunctional uterinebleeding questions to discuss with your doctor from Harvard Medical School

ICD-9ICD-10 Codes

6262 excessive or frequent menstruation

6263 puberty bleeding

6264 irregular menstrual cycle

6265 ovulation bleeding

6266 metrorrhagia

6267 postcoital bleeding

6268 other disorders of menstruation and other abnormalbleeding from female genital tract

6269 unspecified disorders of menstruation and other abnormalbleeding from female genital tract

N92 excessive frequent and irregular menstruation

N920 excessive and frequent menstruation with regular cycle

N921 excessive and frequent menstruation with irregular cycle

N922 excessive menstruation at puberty

N923 ovulation bleeding

N924 excessive bleeding in the premenopausal period

N925 other specified irregular menstruation

N926 irregular menstruation unspecified

N93 other abnormaluterine and vaginal bleeding

N930 postcoital and contact bleeding

N938 other specified abnormaluterine and vaginal bleeding

N939 abnormaluterine and vaginal bleeding unspecified

References

1 Ely JW Kennedy CM Clark EC Bowdler NC Abnormaluterinebleeding a management algorithm J Am Board Fam Med

2006 Nov-Dec19(6)590-602 full-text

2 Casablanca Y Management of dysfunctional uterinebleeding Obstet Gynecol Clin North Am 2008 Jun35(2)219-34 viii

3 Amann M Anguino H Bauman RA et al Chronic abnormaluterinebleeding in nongravid women Pasadena (CA) Kaiser

Permanente Southern California National Guideline Clearinghouse 2007 Oct 2910889

4 National Collaborating Centre for Womenrsquos and Childrenrsquos Health Heavy menstrual bleeding National Institute for Health and

Clinical Excellence (NICE) 2007 JanCG44 PDF

Kaiser Permanente Southern California uses American College of Obstetricians and Gynecologists (ACOG) strength of

recommendation classification

grades of recommendation

Level A - based on good and consistent scientific evidence

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DynaMed editorial process

Special acknowledgements

How to cite

Level B - based on limited or inconsistent scientific evidence

Level C - based primarily on consensus and expert opinion

Reference - Kaiser Permanente Southern California guideline on chronic abnormaluterinebleeding in nongravid women

(National Guideline Clearinghouse 2007 Oct 2910889)

National Institute for Health and Clinical Excellence (NICE) grading system for recommendations

Grade A

at least 1 meta-analysis systematic review or randomized controlled trial (RCT) that is rated 1++ and is directly

applicable to target population or

systematic review of RCTs or body of evidence that consists principally of studies rated 1+ is directly applicable to

target population and demonstrates overall consistency of results or

evidence drawn from NICE technology appraisal

Grade B

body of evidence that includes studies rated 2++ is directly applicable to target population and demonstrates overall

consistency of results or

extrapolated evidence from studies rated 1++ or 1+

Grade C

body of evidence that includes studies rated 2++ is directly applicable to target population and demonstrates overall

consistency of results or

extrapolated evidence from studies rated 2++

Grade D

evidence level 3 or 4 or

extrapolated evidence from studies rated 2+ or

formal consensus

Grade D (GPP) - a good practice point (GPP) is a recommendation for best practice based on experience of Guideline

Development Group

levels of evidence for intervention studies

1++ includes high-quality meta-analyses systematic reviews of RCTs or RCTs with very low risk of bias

1+ includes well-conducted meta-analyses systematic reviews of RCTs or RCTs with low risk of bias

1- includes meta-analyses systematic reviews of RCTs or RCTs with high risk of bias

2++ includes high-quality systematic reviews of case-control or cohort studies high-quality case-control or cohort

studies with very low risk of confounding bias or chance and high probability relationship is casual

2+ includes well-conducted case-control or cohort studies with low risk of confounding bias or chance and moderate

probability relationship is casual

2- includes case-control or cohort studies with high risk of confounding bias or chance and significant risk relationship is

not casual

3 includes nonanalytical studies (for example case reports case series)

4 includes expert opinion formal consensus

Reference - NICE guideline on heavy menstrual bleeding (NICE 2007 JanCG44 PDF)

DynaMed topics are created and maintained by the DynaMed Editorial Team

Over 500 journals and evidence-based sources (DynaMed Content Sources) are monitored directly or indirectly using a 7-Step

evidence-based method for systematic literature surveillance DynaMed topics are updated daily as newly discovered best

available evidence is identified

The participating members of the DynaMed Editorial Team have declared that they have no financial or other competing

interests related to this topic

The participating reviewers have declared that they have no financial or other competing interests related to this topic unless

otherwise indicated

McMaster University is a partner that provides support in identifying Practice-Changing DynaMed Updates Over 1000 practicing

physicians from 61 disciplines in 77 countries rate these articles to help you find the most useful new evidence affecting your

practice

F1000 is a partner that provides support in identifying Practice-Changing DynaMed Updates Over 2000 practicing clinicians from

20 disciplines in 60 countries rate these articles to help you find the most useful new evidence affecting your practice

Linda Feng Chang PharmD MPH BCPS (EPC Course Director and Clinical Assistant Professor of Pharmacy University of Illinois

College of Medicine Illinois United States) provides peer review

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Estaacute viendo un resumen de DynaMed El uso de DynaMed indica la aceptacioacuten de las DynaMed Condiciones de uso Las limitaciones de

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copy 2014 EBSCO Industries Inc Todos los derechos reservados

Page 6: Abnormal uterine bleeding - AEEMmedicina-ucr.com/.../2014/04/Abnormal-Uterine-Bleeding-DynaMed.pdf · Abnormal uterine bleeding ... endometrial ablation preferable to hysterectomy

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Acute severe bleeding

19 prospective cohort studies reviewed including 2917 patients 408 (25) postmenopausal

for detection of any intrauterine pathology statistically significant heterogeneity prevented pooling of likelihood ratios

for detection of submucous fibroids

sonohysterography had pooled likelihood ratio 297 (95 CI 178-496)

hysteroscopy had pooled likelihood ratio 294 (95 CI 134-653)

pooled likelihood ratio for transvaginal ultrasound not calculated because of statistically significant heterogeneity

Reference - Acta Obstet Gynecol Scand 2003 Jun82(6)493 EBSCOhost Full Text

prophylactic vaginal misoprostol may reduce pain in women having outpatient hysteroscopy (level 2 [mid-

level] evidence)

based on randomized trial with allocation concealment not stated

150 women having outpatient hysteroscopy for diagnosis of infertility or abnormaluterinebleeding randomized to cervical

priming with misoprostol 200 mcg vaginally 3 hours before procedure vs no misoprostol

comparing misoprostol vs no misoprostol

mean pain scores (on 0-10 visual analog scale) 326 vs 487 (p lt 0001)

mean procedure time 2 minutes vs 25 minutes (p lt 0001)

misoprostol associated with increased ease of cervical entry and patient acceptability (p le 002 for each)

Reference - Fertil Steril 2011 Oct96(4)962

American Institute of Ultrasound in Medicine (AIUM) guideline on pelvic ultrasound examinations can be found in J Ultrasound

Med 2010 Jan29(1)166

review of evaluation of the endometrium can be found in Obstet Gynecol 2010 Jul116(1)168

Management

indications for hospitalization(1)

orthostatic hypotension

hemoglobin lt 10 gdL

profuse active bleeding

consider blood transfusion if severely anemic(1)

hormonal medication

estrogen

use often recommended but evidence for efficacy is limited(1 2)

IV conjugated equine estrogen may terminate endometrial bleeding in patients with dysfunctional

uterinebleeding (DUB) (level 2 [mid-level] evidence)

based on small randomized trial

34 patients who presented to emergency room with excessive or prolonged uterinebleeding were randomized to

conjugated estrogens (Premarin) 25 mg vs placebo in 5 mL normal saline injected IV over 2 minutes through IV

line running at 75 mLhour

dose repeated (double-blind Premarin or placebo) at 3 hours if bleeding continued

open-label dose of Premarin (regardless of original assignment) at 5 hours if bleeding continued

alternative treatment provided if bleeding continued at 8 hours

comparing estrogen vs placebo

mean duration of bleeding at presentation 141 days (range 1-78) vs 116 days (range 1-90)

bleeding stopped after first injection in 22 vs 36 (not significant)

bleeding stopped after first or second injection in 72 vs 38 (p = 0021 NNT 3)

adverse effects in 39 vs 13 (not significant)

Reference - Obstet Gynecol 1982 Mar59(3)285

DynaMed commentary -- patients had range of bleeding history unclear how many had acute severe bleeding

dose schedules suggested in review article(1)

for inpatient management

conjugated equine estrogens 25 mg in normal saline 50 mL given IV over 20 minutes every 4 hours for 24

hours

at same time start tapered dosing of combination oral contraceptive (ethinyl estradiol 30 mcgnorgestrel 03

mg)

for outpatient management

conjugated equine estrogens 25 mg orally 4 times daily

after acute bleeding stopped start tapered dosing of combination oral contraceptive (ethinyl estradiol 30

mcgnorgestrel 03 mg)

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Irregular menstrual bleeding

tapered dose schedule

1 tablet 4 times daily for 4 days then

1 tablet 3 times daily for 3 days then

1 tablet twice daily for 2 days then

1 tablet once daily for 3 weeks then

1 week off then cycle of oral contraceptives for at least 3 months

oral medroxyprogesterone acetate and combination oral contraceptives appear equally effective in

terminating acute uterinebleeding (level 2 [mid-level] evidence)

based on small randomized trial

40 hemodynamically stable patients with acute uterinebleeding (defined as sufficient to justify immediate medical or

surgical intervention) randomized to

medroxyprogesterone acetate 20 mg orally 3 times daily for 1 week then 20 mg once daily for 3 weeks

monophasic combination oral contraceptive containing norethindrone 1 mg plus ethinyl estradiol 35 mcg 1 tablet 3

times daily for 1 week then 1 tablet once daily for 3 weeks

33 patients (82) evaluated at 14 days

comparing medroxyprogesterone acetate vs combination oral contraceptive

cessation of bleeding achieved in 76 vs 88 (not significant)

median time to bleeding cessation 3 days vs 3 days

emergency surgical procedures avoided in 100 vs 95

no significant differences in incidence of treatment-related nausea and bloating

Reference - Obstet Gynecol 2006 Oct108(4)924

indications for dilatation and curettage or intrauterine Foley bulb placement(1 2)

hemodynamic instability and acute bleeding

lack of response to initial

2 doses of IV estrogen (if inpatient)

4 doses of oral estrogen (if outpatient)

evaluation once patient stabilized(1)

investigation for bleeding disorder (complete blood count platelet count prothrombin time activated partial thromboplastin

time platelet function analysis)

transvaginal ultrasound

medical therapy for irregular menstrual bleeding (presumed anovulatory)

empiric medical management can be started(2)

goal of treatment is to restore natural cycle of endometrial growth and shedding

withdrawal bleeding can be induced by progestin (medroxyprogesterone acetate 5-10 mg daily for 2 weeks every

month)

progestogens given alone (cyclically continuously or nearly continuously) or in combination with estrogens have limited

evidence for management of anovulatory irregular bleeding (Kaiser Level B)(3)

continuing therapy for at least 3 months after stabilization has been suggested for irregular bleeding in nonpregnant

women(1)

no randomized trials found evaluating progestogens alone or in combination with estrogens for irregular or

heavy menstrual bleeding due to anovulation

based on Cochrane review

Reference - Cochrane Database Syst Rev 2012 Sep 12(9)CD001895

metformin and other insulin-sensitizing drugs

role of metformin and other hypoglycemic agents for routine treatment of chronic anovulatory abnormaluterinebleeding

has not been established (Kaiser Level B)(3)

metformin may reduce menstrual abnormalities in women with polycystic ovarian syndrome (PCOS)

metformin may improve menstrual regularity (level 2 [mid-level] evidence) and hormonal markers

(level 3 [lacking direct] evidence) in normal weight normoinsulinemic women with PCOS

based on small randomized trial

28 normal-weight normoinsulinemic women with PCOS randomized to metformin 500 mg twice daily vs

placebo

metformin significantly associated with improved

testosterone levels at 3 and 6 months

17-hydroxyprogesterone levels at 6 months

hirsutism score at 6 months

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reduced ovarian volume at 3 and 6 months

70 in metformin group experienced restoration of menstrual cyclicity

no clinical or hormonal changes with placebo

Reference - Fertil Steril 2010 May 193(7)2303

metformin 850 mg twice daily does not appear to improve menstrual frequency or insulin sensitivity

in obese women with PCOS already making weight loss lifestyle changes (level 2 [mid-level]

evidence)

based on randomized trial with allocation concealment not stated

143 obese oligo-amenorrheic women with PCOS received dietary plan and were randomized to metformin

850 mg twice daily vs placebo for 6 months

metformin significantly reduced waist circumference and free androgen index

no significant difference in

menstrual frequency (both groups improved)

insulin sensitivity

lipid profiles

Reference - Hum Reprod 2006 Jan21(1)80 full-text

metformin may reduce markers of PCOS and menstrual abnormalities

based on small randomized trial

23 women with PCOS randomized to metformin 500 mg vs placebo orally 3 times daily for 6 months

metformin reduced menstrual abnormalities plasma insulin insulin resistance and ovarian hyperandrogenism

no changes in placebo group

warning that ovulation may resume and contraception may be necessary

Reference - J Clin Endocrinol Metab 2000 Jan85(1)139 in Prescribers Letter 2000 Mar7(3)16

metformin associated with higher rate of menses

based on 12-week randomized placebo-controlled trial with 22 patients aged 13-18 years with hyperinsulinemia

and PCOS

Reference - Arch Pediatr Adolesc Med 2006 Mar160(3)241 commentary can be found in Am Fam Physician

2006 Sep 174(5)862

metformin 500-1000 mg twice daily may improve menstrual cyclicity and quality of life in oligo-

amenorrheic women with PCOS (level 2 [mid-level] evidence)

based on cohort study of 64 women (mean age 29 years) with PCOS (all oligoamenorrheic) having

metformin 500-1000 mg twice daily (depending on weight) for 6 months

metformin associated with

normalized menstrual cycle (52 achieved 28-35 cycles)

improved quality of life scores (including domains of vitality social function mental and sexual health)

significant baseline reductions in

insulin resistance

testosterone levels (55 achieved normal levels)

free androgen index levels

body mass index (BMI) (mean decrease 11 kgm )2

no difference in alopecia or hirsutism scores

Reference - Hum Reprod 2006 Jul21(7)1925 full-text

ovulation induction is not indicated (Kaiser Level C)(3)

gonadotropin-releasing hormone (GnRH) agonists may have a role in management of selected women with chronic

anovulatory abnormaluterinebleeding (Kaiser Level B)(3)

lifestyle issues including stress reduction and weight loss might be important in management of abnormaluterinebleeding

associated with anovulatory state (Kaiser Level C)(3)

surgical therapy

surgical therapy for women with chronic dysfunctional uterinebleeding (DUB) is currently reserved for women not interested

in future fertility (Kaiser Level C)(3)

hysterectomy is more effective than endometrial ablation for resolution of symptoms of DUB but has more

adverse perioperative events (level 1 [likely reliable] evidence)

based on randomized trial

237 premenopausal women aged ge 18 years with dysfunctional uterinebleeding randomized to endometrial ablation vs

hysterectomy and followed for up to 5 years

85 were aged lt 45 years

due to funding concerns trial terminated early but gt 80 of women were followed for at least 2 years

1142014 DynaMed

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Heavy menstrual bleeding (menorrhagia)

Other management

primary outcome was resolution of the major reason for which women sought treatment (bleeding pain or fatigue)

comparing endometrial ablation vs hysterectomy

879 vs 932 had major problem solved at 1 year

849 vs 944 had major problem solved at 2 years (p = 0026 NNT 11 favoring hysterectomy)

933 vs 951 had major problem solved at 3 years

851 vs 98 had major problem solved at 4 years (p = 0026 NNT 8 favoring hysterectomy)

109 vs 406 had adverse perioperative events (NNT 4 favoring endometrial ablation)

29 (32 of 110 women) with endometrial ablation required reoperation by 48 months

Reference - STOP-DUB trial (Obstet Gynecol 2007 Dec110(6)1279) correction can be found in Obstet Gynecol 2008

Aug112(2 Pt 1)381 commentary can be found in Obstet Gynecol 2008 Apr111(4)992

for patients with abnormaluterinebleeding due to leiomyomas(3)

surgical management of abnormaluterinebleeding due to leiomyomas is determined by size location and number of

myomas (Kaiser Level C)

selected patients with leiomyoma-related abnormaluterinebleeding who do not wish to retain fertility may be considered

for endometrial ablation (Kaiser Level A)

abdominal myomectomy is the preferred procedure for women with abnormaluterinebleeding related to myomas

unsuitable for resectoscopic removal and who wish to retain their uterus (Kaiser Level C)

symptomatic endometrial polyps should be completely removed under hysteroscopic direction (Kaiser Level B)(3)

improvement in quality of life measures should be goal of any interventions (NICE D recommendation)

clarifying values and patient preferences may reduce hysterectomy rates for menorrhagia (level 2 [mid-level] evidence)

medications

levonorgestrel intrauterine system (LNG-IUS) appears effective for heavy menstrual bleeding (level 2 [mid-level] evidence)

and is treatment of choice if (NICE A recommendation)

hormonal treatments are acceptable

at least 12 months use anticipated

combined oral contraceptives is second-line drug treatment option (NICE B recommendation)

either NSAID or tranexamic acid (Lysteda) considered

second-line treatment option if either hormonal or nonhormonal treatments are acceptable (NICE A recommendation)

preferred treatment option if hormonal treatments are not acceptable (NICE D(GPP) recommendation)

tranexamic acid should not be used before LNG-IUS if long-term use is anticipated (NICE A recommendation)

oral progestins (such as norethisterone 15 mg once daily on menstrual cycle days 5-26) or injected long-acting progestins

considered third-line treatment options (NICE A recommendation)

danazol may be effective for heavy menstrual bleeding (level 2 [mid-level] evidence)

surgeryprocedures

surgery reduces menstrual bleeding at 1 year more than medical therapy but levonorgestrel-intrauterine system improves

quality of life as effectively as surgery (level 1 [likely reliable] evidence)

endometrial ablation

preferable to hysterectomy in women with heavy menstrual bleeding alone and uterus le 10 week pregnancy size

(NICE A recommendation)

preprocedure endometrial thinning may improve operative conditions and amenorrhea at 12 months (level 2 [mid-level]

evidence)

referral for consideration of surgery or uterine artery embolization (UAE) as first-line treatment recommended for women

with large fibroids and heavy menstrual bleeding and other significant symptoms such as dysmenorrhea or pressure

symptoms (NICE D(GPP) recommendation)

UAE myomectomy or hysterectomy should all be considered discussed and documented when surgery for fibroid-related

heavy menstrual bleeding is considered necessary (NICE D(GPP) recommendation)

vaginal hysterectomy preferred over abdominal hysterectomy after incorporating individual assessment (NICE A

recommendation)

DampC should not be used as therapeutic treatment (NICE C recommendation)

see Heavy menstrual bleeding for treatment details

assess need for iron therapy

therapy should be individualized

if needed see Iron deficiency anemia in adults

insufficient evidence for evaluation of use of Chinese herbal medication for dysfunctional uterinebleeding (DUB)

1142014 DynaMed

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Guidelines

United States guidelines

United Kingdom guidelines

Canadian guidelines

European guidelines

Mexican guidelines

Review articles

based on meta-analysis

all except one trial had poor methodological quality

Reference - Evid Based Complement Alternat Med 2009 Mar6(1)99 full-text

Guidelines and Resources

American College of Obstetricians and Gynecologists (ACOG) guidelines

American College of Obstetricians and Gynecologists (ACOG) Practice Bulletin 128 on diagnosis of abnormaluterinebleeding

in reproductive-aged women can be found in Obstet Gynecol 2012 Jul120(1)197 or at National Guideline Clearinghouse

2013 Feb 1138623 commentary can be found in ACOG News Release 2012 Jun 21

American College of Obstetricians and Gynecologists (ACOG) Committee Opinion 557 on management of acute

abnormaluterinebleeding in nonpregnant reproductive-aged women can be found in Obstet Gynecol 2013 Apr121(4)891

ACOG Practice Bulletin 136 on management of abnormaluterinebleeding associated with ovulatory dysfunction can be

found in Obstet Gynecol 2013 Jul122(1)176 or at National Guideline Clearinghouse 2014 Feb 1747451

ACOG Practice Bulletin 81 on endometrial ablation can be found in Obstet Gynecol 2007 May109(5)1233 reaffirmed 2012

Feb or at National Guideline Clearinghouse 2007 Dec 2410918

ACOG Committee Opinion 349 on menstruation on girls and adolescents can be found in Obstet Gynecol 2006

Nov108(5)1323 reaffirmed 2009 Jun also produced by American Academy of Pediatrics (Pediatrics 2006

Nov118(5)2245)

American College of Radiology (ACR) Appropriateness Criteria for abnormal vaginal bleeding can be found at ACR 2010 PDF or

at National Guideline Clearinghouse 2011 Sep 532629

Society of Gynecologic Surgeons (SGS) clinical practice guideline on abnormaluterinebleeding hysterectomy versus alternative

therapy can be found in J Minim Invasive Gynecol 2012 Jan-Feb19(1)81

American College of RadiologyAmerican College of Obstetricians and GynecologistsAmerican Institute of Ultrasound in Medicine

(ACRACOGAIUM) guideline on performance of sonohysterography can be found in J Ultrasound Med 2012 Jan31(1)165 full-

text or at ACRACOGAIUM 2011 PDF

National Institute for Health and Clinical Excellence (NICE) guideline on

heavy menstrual bleeding can be found in NICE 2007 JanCG44 PDF

fluid-filled thermal balloon and microwave endometrial ablation techniques for heavy menstrual bleeding can be found at

NICE 2004 AprTA78

Royal College of Obstetricians and Gynaecologists (RCOG) guideline on best practice in outpatient hysteroscopy can be found

at RCOG 2011 Mar PDF or at National Guideline Clearinghouse 2012 May 1434905

Society of Obstetricians and Gynaecologists of Canada (SOGC) guideline on abnormaluterinebleeding in pre-menopausal women

can be found at SOGC 2013 May 23 PDF or at National Guideline Clearinghouse 2014 Jan 646416

Society of Obstetricians and Gynaecologists of Canada (SOGC) clinical guideline on female sexual health consensus can be

found at SOGC 2012 PDF or at National Guideline Clearinghouse 2013 Jun 338474

Society of Obstetricians and Gynaecologists of Canada (SOGC) recommendations on asymptomatic endometrial thickening can

be found in J Obstet Gynaecol Can 2010 Oct32(10)990 PDF

Alberta Health Services (AHS) clinical practice guideline on uterine sarcoma can be found at AHS 2011 Aug PDF or at National

Guideline Clearinghouse 2013 Mar 438596

Collegravege National des Gyneacutecologues et Obsteacutetriciens Franccedilais (CNGOF) clinical practice guideline on menorrhagia management of

abnormaluterinebleeding before menopause can be found in Eur J Obstet Gynecol Reprod Biol 2010 Oct152(2)133

Mexican School of Obstetrics and Gynecology (Colegio Mexicano de Especialistas en Ginecologa y Obstetricia) clinical practice

guideline on dysfunctional uterinebleeding can be found in Ginecol Obstet Mex 2009 Sep77(9)S231 EBSCOhost Full Text

[Spanish]

review can be found in Am Fam Physician 2004 Apr 1569(8)1915

review can be found in Postgrad Med 2001 Jan109(1)137

review can be found in Am Fam Physician 1999 Oct 160(5)1371

review of managing unscheduled bleeding in non-pregnant premenopausal women can be found in BMJ 2013 Jun 4346f3251

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ICD-9 codes

ICD-10 codes

General references used

Recommendation grading systems used

AHRQ Comparative Effectiveness Review on primary care management of abnormaluterinebleeding 2013 Mar96 PDF

review of abnormaluterinebleeding in premenopausal women can be found in Am Fam Physician 2012 Jan 185(1)35

EBSCOhost Full Text

reviews of terminology controversy can be found in Fertil Steril 2008 Dec90(6)2269 Curr Opin Obstet Gynecol 2007

Dec19(6)591

review of treatment of dysfunctional uterinebleeding can be found in Maturitas 2004 Mar 1547(3)159

review of health-related quality of life work impairment and health-care costs and utilization in abnormaluterinebleeding can be

found in Value Health 2007 May-Jun10(3)183 EBSCOhost Full Text

Patient Information

handout from American College of Obstetricians and Gynecologists PDF

handout from American Society for Reproductive Medicine PDF

handout from American Academy of Family Physicians or in Spanish

handout on dysfunctional uterinebleeding from TeensHealth or in Spanish

technical information on dysfunctional uterinebleeding from Patient Plus PDF

handout on reasons for problem bleeding from Cleveland Clinic

handout on vaginal bleeding from Mayo Clinic

handout on dysfunctional uterinebleeding questions to discuss with your doctor from Harvard Medical School

ICD-9ICD-10 Codes

6262 excessive or frequent menstruation

6263 puberty bleeding

6264 irregular menstrual cycle

6265 ovulation bleeding

6266 metrorrhagia

6267 postcoital bleeding

6268 other disorders of menstruation and other abnormalbleeding from female genital tract

6269 unspecified disorders of menstruation and other abnormalbleeding from female genital tract

N92 excessive frequent and irregular menstruation

N920 excessive and frequent menstruation with regular cycle

N921 excessive and frequent menstruation with irregular cycle

N922 excessive menstruation at puberty

N923 ovulation bleeding

N924 excessive bleeding in the premenopausal period

N925 other specified irregular menstruation

N926 irregular menstruation unspecified

N93 other abnormaluterine and vaginal bleeding

N930 postcoital and contact bleeding

N938 other specified abnormaluterine and vaginal bleeding

N939 abnormaluterine and vaginal bleeding unspecified

References

1 Ely JW Kennedy CM Clark EC Bowdler NC Abnormaluterinebleeding a management algorithm J Am Board Fam Med

2006 Nov-Dec19(6)590-602 full-text

2 Casablanca Y Management of dysfunctional uterinebleeding Obstet Gynecol Clin North Am 2008 Jun35(2)219-34 viii

3 Amann M Anguino H Bauman RA et al Chronic abnormaluterinebleeding in nongravid women Pasadena (CA) Kaiser

Permanente Southern California National Guideline Clearinghouse 2007 Oct 2910889

4 National Collaborating Centre for Womenrsquos and Childrenrsquos Health Heavy menstrual bleeding National Institute for Health and

Clinical Excellence (NICE) 2007 JanCG44 PDF

Kaiser Permanente Southern California uses American College of Obstetricians and Gynecologists (ACOG) strength of

recommendation classification

grades of recommendation

Level A - based on good and consistent scientific evidence

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DynaMed editorial process

Special acknowledgements

How to cite

Level B - based on limited or inconsistent scientific evidence

Level C - based primarily on consensus and expert opinion

Reference - Kaiser Permanente Southern California guideline on chronic abnormaluterinebleeding in nongravid women

(National Guideline Clearinghouse 2007 Oct 2910889)

National Institute for Health and Clinical Excellence (NICE) grading system for recommendations

Grade A

at least 1 meta-analysis systematic review or randomized controlled trial (RCT) that is rated 1++ and is directly

applicable to target population or

systematic review of RCTs or body of evidence that consists principally of studies rated 1+ is directly applicable to

target population and demonstrates overall consistency of results or

evidence drawn from NICE technology appraisal

Grade B

body of evidence that includes studies rated 2++ is directly applicable to target population and demonstrates overall

consistency of results or

extrapolated evidence from studies rated 1++ or 1+

Grade C

body of evidence that includes studies rated 2++ is directly applicable to target population and demonstrates overall

consistency of results or

extrapolated evidence from studies rated 2++

Grade D

evidence level 3 or 4 or

extrapolated evidence from studies rated 2+ or

formal consensus

Grade D (GPP) - a good practice point (GPP) is a recommendation for best practice based on experience of Guideline

Development Group

levels of evidence for intervention studies

1++ includes high-quality meta-analyses systematic reviews of RCTs or RCTs with very low risk of bias

1+ includes well-conducted meta-analyses systematic reviews of RCTs or RCTs with low risk of bias

1- includes meta-analyses systematic reviews of RCTs or RCTs with high risk of bias

2++ includes high-quality systematic reviews of case-control or cohort studies high-quality case-control or cohort

studies with very low risk of confounding bias or chance and high probability relationship is casual

2+ includes well-conducted case-control or cohort studies with low risk of confounding bias or chance and moderate

probability relationship is casual

2- includes case-control or cohort studies with high risk of confounding bias or chance and significant risk relationship is

not casual

3 includes nonanalytical studies (for example case reports case series)

4 includes expert opinion formal consensus

Reference - NICE guideline on heavy menstrual bleeding (NICE 2007 JanCG44 PDF)

DynaMed topics are created and maintained by the DynaMed Editorial Team

Over 500 journals and evidence-based sources (DynaMed Content Sources) are monitored directly or indirectly using a 7-Step

evidence-based method for systematic literature surveillance DynaMed topics are updated daily as newly discovered best

available evidence is identified

The participating members of the DynaMed Editorial Team have declared that they have no financial or other competing

interests related to this topic

The participating reviewers have declared that they have no financial or other competing interests related to this topic unless

otherwise indicated

McMaster University is a partner that provides support in identifying Practice-Changing DynaMed Updates Over 1000 practicing

physicians from 61 disciplines in 77 countries rate these articles to help you find the most useful new evidence affecting your

practice

F1000 is a partner that provides support in identifying Practice-Changing DynaMed Updates Over 2000 practicing clinicians from

20 disciplines in 60 countries rate these articles to help you find the most useful new evidence affecting your practice

Linda Feng Chang PharmD MPH BCPS (EPC Course Director and Clinical Assistant Professor of Pharmacy University of Illinois

College of Medicine Illinois United States) provides peer review

1142014 DynaMed

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Estaacute viendo un resumen de DynaMed El uso de DynaMed indica la aceptacioacuten de las DynaMed Condiciones de uso Las limitaciones de

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For attribution in other publications see How to Cite Information from DynaMed

Parte superior de la paacutegina Sitio de asistencia de EBSCO Claacuteusula de confidencialidad Teacuterminos de uso Copyright

copy 2014 EBSCO Industries Inc Todos los derechos reservados

Page 7: Abnormal uterine bleeding - AEEMmedicina-ucr.com/.../2014/04/Abnormal-Uterine-Bleeding-DynaMed.pdf · Abnormal uterine bleeding ... endometrial ablation preferable to hysterectomy

1142014 DynaMed

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Irregular menstrual bleeding

tapered dose schedule

1 tablet 4 times daily for 4 days then

1 tablet 3 times daily for 3 days then

1 tablet twice daily for 2 days then

1 tablet once daily for 3 weeks then

1 week off then cycle of oral contraceptives for at least 3 months

oral medroxyprogesterone acetate and combination oral contraceptives appear equally effective in

terminating acute uterinebleeding (level 2 [mid-level] evidence)

based on small randomized trial

40 hemodynamically stable patients with acute uterinebleeding (defined as sufficient to justify immediate medical or

surgical intervention) randomized to

medroxyprogesterone acetate 20 mg orally 3 times daily for 1 week then 20 mg once daily for 3 weeks

monophasic combination oral contraceptive containing norethindrone 1 mg plus ethinyl estradiol 35 mcg 1 tablet 3

times daily for 1 week then 1 tablet once daily for 3 weeks

33 patients (82) evaluated at 14 days

comparing medroxyprogesterone acetate vs combination oral contraceptive

cessation of bleeding achieved in 76 vs 88 (not significant)

median time to bleeding cessation 3 days vs 3 days

emergency surgical procedures avoided in 100 vs 95

no significant differences in incidence of treatment-related nausea and bloating

Reference - Obstet Gynecol 2006 Oct108(4)924

indications for dilatation and curettage or intrauterine Foley bulb placement(1 2)

hemodynamic instability and acute bleeding

lack of response to initial

2 doses of IV estrogen (if inpatient)

4 doses of oral estrogen (if outpatient)

evaluation once patient stabilized(1)

investigation for bleeding disorder (complete blood count platelet count prothrombin time activated partial thromboplastin

time platelet function analysis)

transvaginal ultrasound

medical therapy for irregular menstrual bleeding (presumed anovulatory)

empiric medical management can be started(2)

goal of treatment is to restore natural cycle of endometrial growth and shedding

withdrawal bleeding can be induced by progestin (medroxyprogesterone acetate 5-10 mg daily for 2 weeks every

month)

progestogens given alone (cyclically continuously or nearly continuously) or in combination with estrogens have limited

evidence for management of anovulatory irregular bleeding (Kaiser Level B)(3)

continuing therapy for at least 3 months after stabilization has been suggested for irregular bleeding in nonpregnant

women(1)

no randomized trials found evaluating progestogens alone or in combination with estrogens for irregular or

heavy menstrual bleeding due to anovulation

based on Cochrane review

Reference - Cochrane Database Syst Rev 2012 Sep 12(9)CD001895

metformin and other insulin-sensitizing drugs

role of metformin and other hypoglycemic agents for routine treatment of chronic anovulatory abnormaluterinebleeding

has not been established (Kaiser Level B)(3)

metformin may reduce menstrual abnormalities in women with polycystic ovarian syndrome (PCOS)

metformin may improve menstrual regularity (level 2 [mid-level] evidence) and hormonal markers

(level 3 [lacking direct] evidence) in normal weight normoinsulinemic women with PCOS

based on small randomized trial

28 normal-weight normoinsulinemic women with PCOS randomized to metformin 500 mg twice daily vs

placebo

metformin significantly associated with improved

testosterone levels at 3 and 6 months

17-hydroxyprogesterone levels at 6 months

hirsutism score at 6 months

1142014 DynaMed

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reduced ovarian volume at 3 and 6 months

70 in metformin group experienced restoration of menstrual cyclicity

no clinical or hormonal changes with placebo

Reference - Fertil Steril 2010 May 193(7)2303

metformin 850 mg twice daily does not appear to improve menstrual frequency or insulin sensitivity

in obese women with PCOS already making weight loss lifestyle changes (level 2 [mid-level]

evidence)

based on randomized trial with allocation concealment not stated

143 obese oligo-amenorrheic women with PCOS received dietary plan and were randomized to metformin

850 mg twice daily vs placebo for 6 months

metformin significantly reduced waist circumference and free androgen index

no significant difference in

menstrual frequency (both groups improved)

insulin sensitivity

lipid profiles

Reference - Hum Reprod 2006 Jan21(1)80 full-text

metformin may reduce markers of PCOS and menstrual abnormalities

based on small randomized trial

23 women with PCOS randomized to metformin 500 mg vs placebo orally 3 times daily for 6 months

metformin reduced menstrual abnormalities plasma insulin insulin resistance and ovarian hyperandrogenism

no changes in placebo group

warning that ovulation may resume and contraception may be necessary

Reference - J Clin Endocrinol Metab 2000 Jan85(1)139 in Prescribers Letter 2000 Mar7(3)16

metformin associated with higher rate of menses

based on 12-week randomized placebo-controlled trial with 22 patients aged 13-18 years with hyperinsulinemia

and PCOS

Reference - Arch Pediatr Adolesc Med 2006 Mar160(3)241 commentary can be found in Am Fam Physician

2006 Sep 174(5)862

metformin 500-1000 mg twice daily may improve menstrual cyclicity and quality of life in oligo-

amenorrheic women with PCOS (level 2 [mid-level] evidence)

based on cohort study of 64 women (mean age 29 years) with PCOS (all oligoamenorrheic) having

metformin 500-1000 mg twice daily (depending on weight) for 6 months

metformin associated with

normalized menstrual cycle (52 achieved 28-35 cycles)

improved quality of life scores (including domains of vitality social function mental and sexual health)

significant baseline reductions in

insulin resistance

testosterone levels (55 achieved normal levels)

free androgen index levels

body mass index (BMI) (mean decrease 11 kgm )2

no difference in alopecia or hirsutism scores

Reference - Hum Reprod 2006 Jul21(7)1925 full-text

ovulation induction is not indicated (Kaiser Level C)(3)

gonadotropin-releasing hormone (GnRH) agonists may have a role in management of selected women with chronic

anovulatory abnormaluterinebleeding (Kaiser Level B)(3)

lifestyle issues including stress reduction and weight loss might be important in management of abnormaluterinebleeding

associated with anovulatory state (Kaiser Level C)(3)

surgical therapy

surgical therapy for women with chronic dysfunctional uterinebleeding (DUB) is currently reserved for women not interested

in future fertility (Kaiser Level C)(3)

hysterectomy is more effective than endometrial ablation for resolution of symptoms of DUB but has more

adverse perioperative events (level 1 [likely reliable] evidence)

based on randomized trial

237 premenopausal women aged ge 18 years with dysfunctional uterinebleeding randomized to endometrial ablation vs

hysterectomy and followed for up to 5 years

85 were aged lt 45 years

due to funding concerns trial terminated early but gt 80 of women were followed for at least 2 years

1142014 DynaMed

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Heavy menstrual bleeding (menorrhagia)

Other management

primary outcome was resolution of the major reason for which women sought treatment (bleeding pain or fatigue)

comparing endometrial ablation vs hysterectomy

879 vs 932 had major problem solved at 1 year

849 vs 944 had major problem solved at 2 years (p = 0026 NNT 11 favoring hysterectomy)

933 vs 951 had major problem solved at 3 years

851 vs 98 had major problem solved at 4 years (p = 0026 NNT 8 favoring hysterectomy)

109 vs 406 had adverse perioperative events (NNT 4 favoring endometrial ablation)

29 (32 of 110 women) with endometrial ablation required reoperation by 48 months

Reference - STOP-DUB trial (Obstet Gynecol 2007 Dec110(6)1279) correction can be found in Obstet Gynecol 2008

Aug112(2 Pt 1)381 commentary can be found in Obstet Gynecol 2008 Apr111(4)992

for patients with abnormaluterinebleeding due to leiomyomas(3)

surgical management of abnormaluterinebleeding due to leiomyomas is determined by size location and number of

myomas (Kaiser Level C)

selected patients with leiomyoma-related abnormaluterinebleeding who do not wish to retain fertility may be considered

for endometrial ablation (Kaiser Level A)

abdominal myomectomy is the preferred procedure for women with abnormaluterinebleeding related to myomas

unsuitable for resectoscopic removal and who wish to retain their uterus (Kaiser Level C)

symptomatic endometrial polyps should be completely removed under hysteroscopic direction (Kaiser Level B)(3)

improvement in quality of life measures should be goal of any interventions (NICE D recommendation)

clarifying values and patient preferences may reduce hysterectomy rates for menorrhagia (level 2 [mid-level] evidence)

medications

levonorgestrel intrauterine system (LNG-IUS) appears effective for heavy menstrual bleeding (level 2 [mid-level] evidence)

and is treatment of choice if (NICE A recommendation)

hormonal treatments are acceptable

at least 12 months use anticipated

combined oral contraceptives is second-line drug treatment option (NICE B recommendation)

either NSAID or tranexamic acid (Lysteda) considered

second-line treatment option if either hormonal or nonhormonal treatments are acceptable (NICE A recommendation)

preferred treatment option if hormonal treatments are not acceptable (NICE D(GPP) recommendation)

tranexamic acid should not be used before LNG-IUS if long-term use is anticipated (NICE A recommendation)

oral progestins (such as norethisterone 15 mg once daily on menstrual cycle days 5-26) or injected long-acting progestins

considered third-line treatment options (NICE A recommendation)

danazol may be effective for heavy menstrual bleeding (level 2 [mid-level] evidence)

surgeryprocedures

surgery reduces menstrual bleeding at 1 year more than medical therapy but levonorgestrel-intrauterine system improves

quality of life as effectively as surgery (level 1 [likely reliable] evidence)

endometrial ablation

preferable to hysterectomy in women with heavy menstrual bleeding alone and uterus le 10 week pregnancy size

(NICE A recommendation)

preprocedure endometrial thinning may improve operative conditions and amenorrhea at 12 months (level 2 [mid-level]

evidence)

referral for consideration of surgery or uterine artery embolization (UAE) as first-line treatment recommended for women

with large fibroids and heavy menstrual bleeding and other significant symptoms such as dysmenorrhea or pressure

symptoms (NICE D(GPP) recommendation)

UAE myomectomy or hysterectomy should all be considered discussed and documented when surgery for fibroid-related

heavy menstrual bleeding is considered necessary (NICE D(GPP) recommendation)

vaginal hysterectomy preferred over abdominal hysterectomy after incorporating individual assessment (NICE A

recommendation)

DampC should not be used as therapeutic treatment (NICE C recommendation)

see Heavy menstrual bleeding for treatment details

assess need for iron therapy

therapy should be individualized

if needed see Iron deficiency anemia in adults

insufficient evidence for evaluation of use of Chinese herbal medication for dysfunctional uterinebleeding (DUB)

1142014 DynaMed

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Guidelines

United States guidelines

United Kingdom guidelines

Canadian guidelines

European guidelines

Mexican guidelines

Review articles

based on meta-analysis

all except one trial had poor methodological quality

Reference - Evid Based Complement Alternat Med 2009 Mar6(1)99 full-text

Guidelines and Resources

American College of Obstetricians and Gynecologists (ACOG) guidelines

American College of Obstetricians and Gynecologists (ACOG) Practice Bulletin 128 on diagnosis of abnormaluterinebleeding

in reproductive-aged women can be found in Obstet Gynecol 2012 Jul120(1)197 or at National Guideline Clearinghouse

2013 Feb 1138623 commentary can be found in ACOG News Release 2012 Jun 21

American College of Obstetricians and Gynecologists (ACOG) Committee Opinion 557 on management of acute

abnormaluterinebleeding in nonpregnant reproductive-aged women can be found in Obstet Gynecol 2013 Apr121(4)891

ACOG Practice Bulletin 136 on management of abnormaluterinebleeding associated with ovulatory dysfunction can be

found in Obstet Gynecol 2013 Jul122(1)176 or at National Guideline Clearinghouse 2014 Feb 1747451

ACOG Practice Bulletin 81 on endometrial ablation can be found in Obstet Gynecol 2007 May109(5)1233 reaffirmed 2012

Feb or at National Guideline Clearinghouse 2007 Dec 2410918

ACOG Committee Opinion 349 on menstruation on girls and adolescents can be found in Obstet Gynecol 2006

Nov108(5)1323 reaffirmed 2009 Jun also produced by American Academy of Pediatrics (Pediatrics 2006

Nov118(5)2245)

American College of Radiology (ACR) Appropriateness Criteria for abnormal vaginal bleeding can be found at ACR 2010 PDF or

at National Guideline Clearinghouse 2011 Sep 532629

Society of Gynecologic Surgeons (SGS) clinical practice guideline on abnormaluterinebleeding hysterectomy versus alternative

therapy can be found in J Minim Invasive Gynecol 2012 Jan-Feb19(1)81

American College of RadiologyAmerican College of Obstetricians and GynecologistsAmerican Institute of Ultrasound in Medicine

(ACRACOGAIUM) guideline on performance of sonohysterography can be found in J Ultrasound Med 2012 Jan31(1)165 full-

text or at ACRACOGAIUM 2011 PDF

National Institute for Health and Clinical Excellence (NICE) guideline on

heavy menstrual bleeding can be found in NICE 2007 JanCG44 PDF

fluid-filled thermal balloon and microwave endometrial ablation techniques for heavy menstrual bleeding can be found at

NICE 2004 AprTA78

Royal College of Obstetricians and Gynaecologists (RCOG) guideline on best practice in outpatient hysteroscopy can be found

at RCOG 2011 Mar PDF or at National Guideline Clearinghouse 2012 May 1434905

Society of Obstetricians and Gynaecologists of Canada (SOGC) guideline on abnormaluterinebleeding in pre-menopausal women

can be found at SOGC 2013 May 23 PDF or at National Guideline Clearinghouse 2014 Jan 646416

Society of Obstetricians and Gynaecologists of Canada (SOGC) clinical guideline on female sexual health consensus can be

found at SOGC 2012 PDF or at National Guideline Clearinghouse 2013 Jun 338474

Society of Obstetricians and Gynaecologists of Canada (SOGC) recommendations on asymptomatic endometrial thickening can

be found in J Obstet Gynaecol Can 2010 Oct32(10)990 PDF

Alberta Health Services (AHS) clinical practice guideline on uterine sarcoma can be found at AHS 2011 Aug PDF or at National

Guideline Clearinghouse 2013 Mar 438596

Collegravege National des Gyneacutecologues et Obsteacutetriciens Franccedilais (CNGOF) clinical practice guideline on menorrhagia management of

abnormaluterinebleeding before menopause can be found in Eur J Obstet Gynecol Reprod Biol 2010 Oct152(2)133

Mexican School of Obstetrics and Gynecology (Colegio Mexicano de Especialistas en Ginecologa y Obstetricia) clinical practice

guideline on dysfunctional uterinebleeding can be found in Ginecol Obstet Mex 2009 Sep77(9)S231 EBSCOhost Full Text

[Spanish]

review can be found in Am Fam Physician 2004 Apr 1569(8)1915

review can be found in Postgrad Med 2001 Jan109(1)137

review can be found in Am Fam Physician 1999 Oct 160(5)1371

review of managing unscheduled bleeding in non-pregnant premenopausal women can be found in BMJ 2013 Jun 4346f3251

1142014 DynaMed

httpwebbebscohostcomezproxysibdiucraccr2048dynameddeliveryprintcitationexpand=sec-General-Informationsec-Causessec-History-and-Physicahellip 1113

ICD-9 codes

ICD-10 codes

General references used

Recommendation grading systems used

AHRQ Comparative Effectiveness Review on primary care management of abnormaluterinebleeding 2013 Mar96 PDF

review of abnormaluterinebleeding in premenopausal women can be found in Am Fam Physician 2012 Jan 185(1)35

EBSCOhost Full Text

reviews of terminology controversy can be found in Fertil Steril 2008 Dec90(6)2269 Curr Opin Obstet Gynecol 2007

Dec19(6)591

review of treatment of dysfunctional uterinebleeding can be found in Maturitas 2004 Mar 1547(3)159

review of health-related quality of life work impairment and health-care costs and utilization in abnormaluterinebleeding can be

found in Value Health 2007 May-Jun10(3)183 EBSCOhost Full Text

Patient Information

handout from American College of Obstetricians and Gynecologists PDF

handout from American Society for Reproductive Medicine PDF

handout from American Academy of Family Physicians or in Spanish

handout on dysfunctional uterinebleeding from TeensHealth or in Spanish

technical information on dysfunctional uterinebleeding from Patient Plus PDF

handout on reasons for problem bleeding from Cleveland Clinic

handout on vaginal bleeding from Mayo Clinic

handout on dysfunctional uterinebleeding questions to discuss with your doctor from Harvard Medical School

ICD-9ICD-10 Codes

6262 excessive or frequent menstruation

6263 puberty bleeding

6264 irregular menstrual cycle

6265 ovulation bleeding

6266 metrorrhagia

6267 postcoital bleeding

6268 other disorders of menstruation and other abnormalbleeding from female genital tract

6269 unspecified disorders of menstruation and other abnormalbleeding from female genital tract

N92 excessive frequent and irregular menstruation

N920 excessive and frequent menstruation with regular cycle

N921 excessive and frequent menstruation with irregular cycle

N922 excessive menstruation at puberty

N923 ovulation bleeding

N924 excessive bleeding in the premenopausal period

N925 other specified irregular menstruation

N926 irregular menstruation unspecified

N93 other abnormaluterine and vaginal bleeding

N930 postcoital and contact bleeding

N938 other specified abnormaluterine and vaginal bleeding

N939 abnormaluterine and vaginal bleeding unspecified

References

1 Ely JW Kennedy CM Clark EC Bowdler NC Abnormaluterinebleeding a management algorithm J Am Board Fam Med

2006 Nov-Dec19(6)590-602 full-text

2 Casablanca Y Management of dysfunctional uterinebleeding Obstet Gynecol Clin North Am 2008 Jun35(2)219-34 viii

3 Amann M Anguino H Bauman RA et al Chronic abnormaluterinebleeding in nongravid women Pasadena (CA) Kaiser

Permanente Southern California National Guideline Clearinghouse 2007 Oct 2910889

4 National Collaborating Centre for Womenrsquos and Childrenrsquos Health Heavy menstrual bleeding National Institute for Health and

Clinical Excellence (NICE) 2007 JanCG44 PDF

Kaiser Permanente Southern California uses American College of Obstetricians and Gynecologists (ACOG) strength of

recommendation classification

grades of recommendation

Level A - based on good and consistent scientific evidence

1142014 DynaMed

httpwebbebscohostcomezproxysibdiucraccr2048dynameddeliveryprintcitationexpand=sec-General-Informationsec-Causessec-History-and-Physicahellip 1213

DynaMed editorial process

Special acknowledgements

How to cite

Level B - based on limited or inconsistent scientific evidence

Level C - based primarily on consensus and expert opinion

Reference - Kaiser Permanente Southern California guideline on chronic abnormaluterinebleeding in nongravid women

(National Guideline Clearinghouse 2007 Oct 2910889)

National Institute for Health and Clinical Excellence (NICE) grading system for recommendations

Grade A

at least 1 meta-analysis systematic review or randomized controlled trial (RCT) that is rated 1++ and is directly

applicable to target population or

systematic review of RCTs or body of evidence that consists principally of studies rated 1+ is directly applicable to

target population and demonstrates overall consistency of results or

evidence drawn from NICE technology appraisal

Grade B

body of evidence that includes studies rated 2++ is directly applicable to target population and demonstrates overall

consistency of results or

extrapolated evidence from studies rated 1++ or 1+

Grade C

body of evidence that includes studies rated 2++ is directly applicable to target population and demonstrates overall

consistency of results or

extrapolated evidence from studies rated 2++

Grade D

evidence level 3 or 4 or

extrapolated evidence from studies rated 2+ or

formal consensus

Grade D (GPP) - a good practice point (GPP) is a recommendation for best practice based on experience of Guideline

Development Group

levels of evidence for intervention studies

1++ includes high-quality meta-analyses systematic reviews of RCTs or RCTs with very low risk of bias

1+ includes well-conducted meta-analyses systematic reviews of RCTs or RCTs with low risk of bias

1- includes meta-analyses systematic reviews of RCTs or RCTs with high risk of bias

2++ includes high-quality systematic reviews of case-control or cohort studies high-quality case-control or cohort

studies with very low risk of confounding bias or chance and high probability relationship is casual

2+ includes well-conducted case-control or cohort studies with low risk of confounding bias or chance and moderate

probability relationship is casual

2- includes case-control or cohort studies with high risk of confounding bias or chance and significant risk relationship is

not casual

3 includes nonanalytical studies (for example case reports case series)

4 includes expert opinion formal consensus

Reference - NICE guideline on heavy menstrual bleeding (NICE 2007 JanCG44 PDF)

DynaMed topics are created and maintained by the DynaMed Editorial Team

Over 500 journals and evidence-based sources (DynaMed Content Sources) are monitored directly or indirectly using a 7-Step

evidence-based method for systematic literature surveillance DynaMed topics are updated daily as newly discovered best

available evidence is identified

The participating members of the DynaMed Editorial Team have declared that they have no financial or other competing

interests related to this topic

The participating reviewers have declared that they have no financial or other competing interests related to this topic unless

otherwise indicated

McMaster University is a partner that provides support in identifying Practice-Changing DynaMed Updates Over 1000 practicing

physicians from 61 disciplines in 77 countries rate these articles to help you find the most useful new evidence affecting your

practice

F1000 is a partner that provides support in identifying Practice-Changing DynaMed Updates Over 2000 practicing clinicians from

20 disciplines in 60 countries rate these articles to help you find the most useful new evidence affecting your practice

Linda Feng Chang PharmD MPH BCPS (EPC Course Director and Clinical Assistant Professor of Pharmacy University of Illinois

College of Medicine Illinois United States) provides peer review

1142014 DynaMed

httpwebbebscohostcomezproxysibdiucraccr2048dynameddeliveryprintcitationexpand=sec-General-Informationsec-Causessec-History-and-Physicahellip 1313

Estaacute viendo un resumen de DynaMed El uso de DynaMed indica la aceptacioacuten de las DynaMed Condiciones de uso Las limitaciones de

DynaMed se encuentran en las Condiciones de uso de DynaMed

Haga sus comentarios enviando un correo electroacutenico para DynaMed a DynaMedEditorebscohostcom

For attribution in other publications see How to Cite Information from DynaMed

Parte superior de la paacutegina Sitio de asistencia de EBSCO Claacuteusula de confidencialidad Teacuterminos de uso Copyright

copy 2014 EBSCO Industries Inc Todos los derechos reservados

Page 8: Abnormal uterine bleeding - AEEMmedicina-ucr.com/.../2014/04/Abnormal-Uterine-Bleeding-DynaMed.pdf · Abnormal uterine bleeding ... endometrial ablation preferable to hysterectomy

1142014 DynaMed

httpwebbebscohostcomezproxysibdiucraccr2048dynameddeliveryprintcitationexpand=sec-General-Informationsec-Causessec-History-and-Physicalhellip 813

reduced ovarian volume at 3 and 6 months

70 in metformin group experienced restoration of menstrual cyclicity

no clinical or hormonal changes with placebo

Reference - Fertil Steril 2010 May 193(7)2303

metformin 850 mg twice daily does not appear to improve menstrual frequency or insulin sensitivity

in obese women with PCOS already making weight loss lifestyle changes (level 2 [mid-level]

evidence)

based on randomized trial with allocation concealment not stated

143 obese oligo-amenorrheic women with PCOS received dietary plan and were randomized to metformin

850 mg twice daily vs placebo for 6 months

metformin significantly reduced waist circumference and free androgen index

no significant difference in

menstrual frequency (both groups improved)

insulin sensitivity

lipid profiles

Reference - Hum Reprod 2006 Jan21(1)80 full-text

metformin may reduce markers of PCOS and menstrual abnormalities

based on small randomized trial

23 women with PCOS randomized to metformin 500 mg vs placebo orally 3 times daily for 6 months

metformin reduced menstrual abnormalities plasma insulin insulin resistance and ovarian hyperandrogenism

no changes in placebo group

warning that ovulation may resume and contraception may be necessary

Reference - J Clin Endocrinol Metab 2000 Jan85(1)139 in Prescribers Letter 2000 Mar7(3)16

metformin associated with higher rate of menses

based on 12-week randomized placebo-controlled trial with 22 patients aged 13-18 years with hyperinsulinemia

and PCOS

Reference - Arch Pediatr Adolesc Med 2006 Mar160(3)241 commentary can be found in Am Fam Physician

2006 Sep 174(5)862

metformin 500-1000 mg twice daily may improve menstrual cyclicity and quality of life in oligo-

amenorrheic women with PCOS (level 2 [mid-level] evidence)

based on cohort study of 64 women (mean age 29 years) with PCOS (all oligoamenorrheic) having

metformin 500-1000 mg twice daily (depending on weight) for 6 months

metformin associated with

normalized menstrual cycle (52 achieved 28-35 cycles)

improved quality of life scores (including domains of vitality social function mental and sexual health)

significant baseline reductions in

insulin resistance

testosterone levels (55 achieved normal levels)

free androgen index levels

body mass index (BMI) (mean decrease 11 kgm )2

no difference in alopecia or hirsutism scores

Reference - Hum Reprod 2006 Jul21(7)1925 full-text

ovulation induction is not indicated (Kaiser Level C)(3)

gonadotropin-releasing hormone (GnRH) agonists may have a role in management of selected women with chronic

anovulatory abnormaluterinebleeding (Kaiser Level B)(3)

lifestyle issues including stress reduction and weight loss might be important in management of abnormaluterinebleeding

associated with anovulatory state (Kaiser Level C)(3)

surgical therapy

surgical therapy for women with chronic dysfunctional uterinebleeding (DUB) is currently reserved for women not interested

in future fertility (Kaiser Level C)(3)

hysterectomy is more effective than endometrial ablation for resolution of symptoms of DUB but has more

adverse perioperative events (level 1 [likely reliable] evidence)

based on randomized trial

237 premenopausal women aged ge 18 years with dysfunctional uterinebleeding randomized to endometrial ablation vs

hysterectomy and followed for up to 5 years

85 were aged lt 45 years

due to funding concerns trial terminated early but gt 80 of women were followed for at least 2 years

1142014 DynaMed

httpwebbebscohostcomezproxysibdiucraccr2048dynameddeliveryprintcitationexpand=sec-General-Informationsec-Causessec-History-and-Physicalhellip 913

Heavy menstrual bleeding (menorrhagia)

Other management

primary outcome was resolution of the major reason for which women sought treatment (bleeding pain or fatigue)

comparing endometrial ablation vs hysterectomy

879 vs 932 had major problem solved at 1 year

849 vs 944 had major problem solved at 2 years (p = 0026 NNT 11 favoring hysterectomy)

933 vs 951 had major problem solved at 3 years

851 vs 98 had major problem solved at 4 years (p = 0026 NNT 8 favoring hysterectomy)

109 vs 406 had adverse perioperative events (NNT 4 favoring endometrial ablation)

29 (32 of 110 women) with endometrial ablation required reoperation by 48 months

Reference - STOP-DUB trial (Obstet Gynecol 2007 Dec110(6)1279) correction can be found in Obstet Gynecol 2008

Aug112(2 Pt 1)381 commentary can be found in Obstet Gynecol 2008 Apr111(4)992

for patients with abnormaluterinebleeding due to leiomyomas(3)

surgical management of abnormaluterinebleeding due to leiomyomas is determined by size location and number of

myomas (Kaiser Level C)

selected patients with leiomyoma-related abnormaluterinebleeding who do not wish to retain fertility may be considered

for endometrial ablation (Kaiser Level A)

abdominal myomectomy is the preferred procedure for women with abnormaluterinebleeding related to myomas

unsuitable for resectoscopic removal and who wish to retain their uterus (Kaiser Level C)

symptomatic endometrial polyps should be completely removed under hysteroscopic direction (Kaiser Level B)(3)

improvement in quality of life measures should be goal of any interventions (NICE D recommendation)

clarifying values and patient preferences may reduce hysterectomy rates for menorrhagia (level 2 [mid-level] evidence)

medications

levonorgestrel intrauterine system (LNG-IUS) appears effective for heavy menstrual bleeding (level 2 [mid-level] evidence)

and is treatment of choice if (NICE A recommendation)

hormonal treatments are acceptable

at least 12 months use anticipated

combined oral contraceptives is second-line drug treatment option (NICE B recommendation)

either NSAID or tranexamic acid (Lysteda) considered

second-line treatment option if either hormonal or nonhormonal treatments are acceptable (NICE A recommendation)

preferred treatment option if hormonal treatments are not acceptable (NICE D(GPP) recommendation)

tranexamic acid should not be used before LNG-IUS if long-term use is anticipated (NICE A recommendation)

oral progestins (such as norethisterone 15 mg once daily on menstrual cycle days 5-26) or injected long-acting progestins

considered third-line treatment options (NICE A recommendation)

danazol may be effective for heavy menstrual bleeding (level 2 [mid-level] evidence)

surgeryprocedures

surgery reduces menstrual bleeding at 1 year more than medical therapy but levonorgestrel-intrauterine system improves

quality of life as effectively as surgery (level 1 [likely reliable] evidence)

endometrial ablation

preferable to hysterectomy in women with heavy menstrual bleeding alone and uterus le 10 week pregnancy size

(NICE A recommendation)

preprocedure endometrial thinning may improve operative conditions and amenorrhea at 12 months (level 2 [mid-level]

evidence)

referral for consideration of surgery or uterine artery embolization (UAE) as first-line treatment recommended for women

with large fibroids and heavy menstrual bleeding and other significant symptoms such as dysmenorrhea or pressure

symptoms (NICE D(GPP) recommendation)

UAE myomectomy or hysterectomy should all be considered discussed and documented when surgery for fibroid-related

heavy menstrual bleeding is considered necessary (NICE D(GPP) recommendation)

vaginal hysterectomy preferred over abdominal hysterectomy after incorporating individual assessment (NICE A

recommendation)

DampC should not be used as therapeutic treatment (NICE C recommendation)

see Heavy menstrual bleeding for treatment details

assess need for iron therapy

therapy should be individualized

if needed see Iron deficiency anemia in adults

insufficient evidence for evaluation of use of Chinese herbal medication for dysfunctional uterinebleeding (DUB)

1142014 DynaMed

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Guidelines

United States guidelines

United Kingdom guidelines

Canadian guidelines

European guidelines

Mexican guidelines

Review articles

based on meta-analysis

all except one trial had poor methodological quality

Reference - Evid Based Complement Alternat Med 2009 Mar6(1)99 full-text

Guidelines and Resources

American College of Obstetricians and Gynecologists (ACOG) guidelines

American College of Obstetricians and Gynecologists (ACOG) Practice Bulletin 128 on diagnosis of abnormaluterinebleeding

in reproductive-aged women can be found in Obstet Gynecol 2012 Jul120(1)197 or at National Guideline Clearinghouse

2013 Feb 1138623 commentary can be found in ACOG News Release 2012 Jun 21

American College of Obstetricians and Gynecologists (ACOG) Committee Opinion 557 on management of acute

abnormaluterinebleeding in nonpregnant reproductive-aged women can be found in Obstet Gynecol 2013 Apr121(4)891

ACOG Practice Bulletin 136 on management of abnormaluterinebleeding associated with ovulatory dysfunction can be

found in Obstet Gynecol 2013 Jul122(1)176 or at National Guideline Clearinghouse 2014 Feb 1747451

ACOG Practice Bulletin 81 on endometrial ablation can be found in Obstet Gynecol 2007 May109(5)1233 reaffirmed 2012

Feb or at National Guideline Clearinghouse 2007 Dec 2410918

ACOG Committee Opinion 349 on menstruation on girls and adolescents can be found in Obstet Gynecol 2006

Nov108(5)1323 reaffirmed 2009 Jun also produced by American Academy of Pediatrics (Pediatrics 2006

Nov118(5)2245)

American College of Radiology (ACR) Appropriateness Criteria for abnormal vaginal bleeding can be found at ACR 2010 PDF or

at National Guideline Clearinghouse 2011 Sep 532629

Society of Gynecologic Surgeons (SGS) clinical practice guideline on abnormaluterinebleeding hysterectomy versus alternative

therapy can be found in J Minim Invasive Gynecol 2012 Jan-Feb19(1)81

American College of RadiologyAmerican College of Obstetricians and GynecologistsAmerican Institute of Ultrasound in Medicine

(ACRACOGAIUM) guideline on performance of sonohysterography can be found in J Ultrasound Med 2012 Jan31(1)165 full-

text or at ACRACOGAIUM 2011 PDF

National Institute for Health and Clinical Excellence (NICE) guideline on

heavy menstrual bleeding can be found in NICE 2007 JanCG44 PDF

fluid-filled thermal balloon and microwave endometrial ablation techniques for heavy menstrual bleeding can be found at

NICE 2004 AprTA78

Royal College of Obstetricians and Gynaecologists (RCOG) guideline on best practice in outpatient hysteroscopy can be found

at RCOG 2011 Mar PDF or at National Guideline Clearinghouse 2012 May 1434905

Society of Obstetricians and Gynaecologists of Canada (SOGC) guideline on abnormaluterinebleeding in pre-menopausal women

can be found at SOGC 2013 May 23 PDF or at National Guideline Clearinghouse 2014 Jan 646416

Society of Obstetricians and Gynaecologists of Canada (SOGC) clinical guideline on female sexual health consensus can be

found at SOGC 2012 PDF or at National Guideline Clearinghouse 2013 Jun 338474

Society of Obstetricians and Gynaecologists of Canada (SOGC) recommendations on asymptomatic endometrial thickening can

be found in J Obstet Gynaecol Can 2010 Oct32(10)990 PDF

Alberta Health Services (AHS) clinical practice guideline on uterine sarcoma can be found at AHS 2011 Aug PDF or at National

Guideline Clearinghouse 2013 Mar 438596

Collegravege National des Gyneacutecologues et Obsteacutetriciens Franccedilais (CNGOF) clinical practice guideline on menorrhagia management of

abnormaluterinebleeding before menopause can be found in Eur J Obstet Gynecol Reprod Biol 2010 Oct152(2)133

Mexican School of Obstetrics and Gynecology (Colegio Mexicano de Especialistas en Ginecologa y Obstetricia) clinical practice

guideline on dysfunctional uterinebleeding can be found in Ginecol Obstet Mex 2009 Sep77(9)S231 EBSCOhost Full Text

[Spanish]

review can be found in Am Fam Physician 2004 Apr 1569(8)1915

review can be found in Postgrad Med 2001 Jan109(1)137

review can be found in Am Fam Physician 1999 Oct 160(5)1371

review of managing unscheduled bleeding in non-pregnant premenopausal women can be found in BMJ 2013 Jun 4346f3251

1142014 DynaMed

httpwebbebscohostcomezproxysibdiucraccr2048dynameddeliveryprintcitationexpand=sec-General-Informationsec-Causessec-History-and-Physicahellip 1113

ICD-9 codes

ICD-10 codes

General references used

Recommendation grading systems used

AHRQ Comparative Effectiveness Review on primary care management of abnormaluterinebleeding 2013 Mar96 PDF

review of abnormaluterinebleeding in premenopausal women can be found in Am Fam Physician 2012 Jan 185(1)35

EBSCOhost Full Text

reviews of terminology controversy can be found in Fertil Steril 2008 Dec90(6)2269 Curr Opin Obstet Gynecol 2007

Dec19(6)591

review of treatment of dysfunctional uterinebleeding can be found in Maturitas 2004 Mar 1547(3)159

review of health-related quality of life work impairment and health-care costs and utilization in abnormaluterinebleeding can be

found in Value Health 2007 May-Jun10(3)183 EBSCOhost Full Text

Patient Information

handout from American College of Obstetricians and Gynecologists PDF

handout from American Society for Reproductive Medicine PDF

handout from American Academy of Family Physicians or in Spanish

handout on dysfunctional uterinebleeding from TeensHealth or in Spanish

technical information on dysfunctional uterinebleeding from Patient Plus PDF

handout on reasons for problem bleeding from Cleveland Clinic

handout on vaginal bleeding from Mayo Clinic

handout on dysfunctional uterinebleeding questions to discuss with your doctor from Harvard Medical School

ICD-9ICD-10 Codes

6262 excessive or frequent menstruation

6263 puberty bleeding

6264 irregular menstrual cycle

6265 ovulation bleeding

6266 metrorrhagia

6267 postcoital bleeding

6268 other disorders of menstruation and other abnormalbleeding from female genital tract

6269 unspecified disorders of menstruation and other abnormalbleeding from female genital tract

N92 excessive frequent and irregular menstruation

N920 excessive and frequent menstruation with regular cycle

N921 excessive and frequent menstruation with irregular cycle

N922 excessive menstruation at puberty

N923 ovulation bleeding

N924 excessive bleeding in the premenopausal period

N925 other specified irregular menstruation

N926 irregular menstruation unspecified

N93 other abnormaluterine and vaginal bleeding

N930 postcoital and contact bleeding

N938 other specified abnormaluterine and vaginal bleeding

N939 abnormaluterine and vaginal bleeding unspecified

References

1 Ely JW Kennedy CM Clark EC Bowdler NC Abnormaluterinebleeding a management algorithm J Am Board Fam Med

2006 Nov-Dec19(6)590-602 full-text

2 Casablanca Y Management of dysfunctional uterinebleeding Obstet Gynecol Clin North Am 2008 Jun35(2)219-34 viii

3 Amann M Anguino H Bauman RA et al Chronic abnormaluterinebleeding in nongravid women Pasadena (CA) Kaiser

Permanente Southern California National Guideline Clearinghouse 2007 Oct 2910889

4 National Collaborating Centre for Womenrsquos and Childrenrsquos Health Heavy menstrual bleeding National Institute for Health and

Clinical Excellence (NICE) 2007 JanCG44 PDF

Kaiser Permanente Southern California uses American College of Obstetricians and Gynecologists (ACOG) strength of

recommendation classification

grades of recommendation

Level A - based on good and consistent scientific evidence

1142014 DynaMed

httpwebbebscohostcomezproxysibdiucraccr2048dynameddeliveryprintcitationexpand=sec-General-Informationsec-Causessec-History-and-Physicahellip 1213

DynaMed editorial process

Special acknowledgements

How to cite

Level B - based on limited or inconsistent scientific evidence

Level C - based primarily on consensus and expert opinion

Reference - Kaiser Permanente Southern California guideline on chronic abnormaluterinebleeding in nongravid women

(National Guideline Clearinghouse 2007 Oct 2910889)

National Institute for Health and Clinical Excellence (NICE) grading system for recommendations

Grade A

at least 1 meta-analysis systematic review or randomized controlled trial (RCT) that is rated 1++ and is directly

applicable to target population or

systematic review of RCTs or body of evidence that consists principally of studies rated 1+ is directly applicable to

target population and demonstrates overall consistency of results or

evidence drawn from NICE technology appraisal

Grade B

body of evidence that includes studies rated 2++ is directly applicable to target population and demonstrates overall

consistency of results or

extrapolated evidence from studies rated 1++ or 1+

Grade C

body of evidence that includes studies rated 2++ is directly applicable to target population and demonstrates overall

consistency of results or

extrapolated evidence from studies rated 2++

Grade D

evidence level 3 or 4 or

extrapolated evidence from studies rated 2+ or

formal consensus

Grade D (GPP) - a good practice point (GPP) is a recommendation for best practice based on experience of Guideline

Development Group

levels of evidence for intervention studies

1++ includes high-quality meta-analyses systematic reviews of RCTs or RCTs with very low risk of bias

1+ includes well-conducted meta-analyses systematic reviews of RCTs or RCTs with low risk of bias

1- includes meta-analyses systematic reviews of RCTs or RCTs with high risk of bias

2++ includes high-quality systematic reviews of case-control or cohort studies high-quality case-control or cohort

studies with very low risk of confounding bias or chance and high probability relationship is casual

2+ includes well-conducted case-control or cohort studies with low risk of confounding bias or chance and moderate

probability relationship is casual

2- includes case-control or cohort studies with high risk of confounding bias or chance and significant risk relationship is

not casual

3 includes nonanalytical studies (for example case reports case series)

4 includes expert opinion formal consensus

Reference - NICE guideline on heavy menstrual bleeding (NICE 2007 JanCG44 PDF)

DynaMed topics are created and maintained by the DynaMed Editorial Team

Over 500 journals and evidence-based sources (DynaMed Content Sources) are monitored directly or indirectly using a 7-Step

evidence-based method for systematic literature surveillance DynaMed topics are updated daily as newly discovered best

available evidence is identified

The participating members of the DynaMed Editorial Team have declared that they have no financial or other competing

interests related to this topic

The participating reviewers have declared that they have no financial or other competing interests related to this topic unless

otherwise indicated

McMaster University is a partner that provides support in identifying Practice-Changing DynaMed Updates Over 1000 practicing

physicians from 61 disciplines in 77 countries rate these articles to help you find the most useful new evidence affecting your

practice

F1000 is a partner that provides support in identifying Practice-Changing DynaMed Updates Over 2000 practicing clinicians from

20 disciplines in 60 countries rate these articles to help you find the most useful new evidence affecting your practice

Linda Feng Chang PharmD MPH BCPS (EPC Course Director and Clinical Assistant Professor of Pharmacy University of Illinois

College of Medicine Illinois United States) provides peer review

1142014 DynaMed

httpwebbebscohostcomezproxysibdiucraccr2048dynameddeliveryprintcitationexpand=sec-General-Informationsec-Causessec-History-and-Physicahellip 1313

Estaacute viendo un resumen de DynaMed El uso de DynaMed indica la aceptacioacuten de las DynaMed Condiciones de uso Las limitaciones de

DynaMed se encuentran en las Condiciones de uso de DynaMed

Haga sus comentarios enviando un correo electroacutenico para DynaMed a DynaMedEditorebscohostcom

For attribution in other publications see How to Cite Information from DynaMed

Parte superior de la paacutegina Sitio de asistencia de EBSCO Claacuteusula de confidencialidad Teacuterminos de uso Copyright

copy 2014 EBSCO Industries Inc Todos los derechos reservados

Page 9: Abnormal uterine bleeding - AEEMmedicina-ucr.com/.../2014/04/Abnormal-Uterine-Bleeding-DynaMed.pdf · Abnormal uterine bleeding ... endometrial ablation preferable to hysterectomy

1142014 DynaMed

httpwebbebscohostcomezproxysibdiucraccr2048dynameddeliveryprintcitationexpand=sec-General-Informationsec-Causessec-History-and-Physicalhellip 913

Heavy menstrual bleeding (menorrhagia)

Other management

primary outcome was resolution of the major reason for which women sought treatment (bleeding pain or fatigue)

comparing endometrial ablation vs hysterectomy

879 vs 932 had major problem solved at 1 year

849 vs 944 had major problem solved at 2 years (p = 0026 NNT 11 favoring hysterectomy)

933 vs 951 had major problem solved at 3 years

851 vs 98 had major problem solved at 4 years (p = 0026 NNT 8 favoring hysterectomy)

109 vs 406 had adverse perioperative events (NNT 4 favoring endometrial ablation)

29 (32 of 110 women) with endometrial ablation required reoperation by 48 months

Reference - STOP-DUB trial (Obstet Gynecol 2007 Dec110(6)1279) correction can be found in Obstet Gynecol 2008

Aug112(2 Pt 1)381 commentary can be found in Obstet Gynecol 2008 Apr111(4)992

for patients with abnormaluterinebleeding due to leiomyomas(3)

surgical management of abnormaluterinebleeding due to leiomyomas is determined by size location and number of

myomas (Kaiser Level C)

selected patients with leiomyoma-related abnormaluterinebleeding who do not wish to retain fertility may be considered

for endometrial ablation (Kaiser Level A)

abdominal myomectomy is the preferred procedure for women with abnormaluterinebleeding related to myomas

unsuitable for resectoscopic removal and who wish to retain their uterus (Kaiser Level C)

symptomatic endometrial polyps should be completely removed under hysteroscopic direction (Kaiser Level B)(3)

improvement in quality of life measures should be goal of any interventions (NICE D recommendation)

clarifying values and patient preferences may reduce hysterectomy rates for menorrhagia (level 2 [mid-level] evidence)

medications

levonorgestrel intrauterine system (LNG-IUS) appears effective for heavy menstrual bleeding (level 2 [mid-level] evidence)

and is treatment of choice if (NICE A recommendation)

hormonal treatments are acceptable

at least 12 months use anticipated

combined oral contraceptives is second-line drug treatment option (NICE B recommendation)

either NSAID or tranexamic acid (Lysteda) considered

second-line treatment option if either hormonal or nonhormonal treatments are acceptable (NICE A recommendation)

preferred treatment option if hormonal treatments are not acceptable (NICE D(GPP) recommendation)

tranexamic acid should not be used before LNG-IUS if long-term use is anticipated (NICE A recommendation)

oral progestins (such as norethisterone 15 mg once daily on menstrual cycle days 5-26) or injected long-acting progestins

considered third-line treatment options (NICE A recommendation)

danazol may be effective for heavy menstrual bleeding (level 2 [mid-level] evidence)

surgeryprocedures

surgery reduces menstrual bleeding at 1 year more than medical therapy but levonorgestrel-intrauterine system improves

quality of life as effectively as surgery (level 1 [likely reliable] evidence)

endometrial ablation

preferable to hysterectomy in women with heavy menstrual bleeding alone and uterus le 10 week pregnancy size

(NICE A recommendation)

preprocedure endometrial thinning may improve operative conditions and amenorrhea at 12 months (level 2 [mid-level]

evidence)

referral for consideration of surgery or uterine artery embolization (UAE) as first-line treatment recommended for women

with large fibroids and heavy menstrual bleeding and other significant symptoms such as dysmenorrhea or pressure

symptoms (NICE D(GPP) recommendation)

UAE myomectomy or hysterectomy should all be considered discussed and documented when surgery for fibroid-related

heavy menstrual bleeding is considered necessary (NICE D(GPP) recommendation)

vaginal hysterectomy preferred over abdominal hysterectomy after incorporating individual assessment (NICE A

recommendation)

DampC should not be used as therapeutic treatment (NICE C recommendation)

see Heavy menstrual bleeding for treatment details

assess need for iron therapy

therapy should be individualized

if needed see Iron deficiency anemia in adults

insufficient evidence for evaluation of use of Chinese herbal medication for dysfunctional uterinebleeding (DUB)

1142014 DynaMed

httpwebbebscohostcomezproxysibdiucraccr2048dynameddeliveryprintcitationexpand=sec-General-Informationsec-Causessec-History-and-Physicahellip 1013

Guidelines

United States guidelines

United Kingdom guidelines

Canadian guidelines

European guidelines

Mexican guidelines

Review articles

based on meta-analysis

all except one trial had poor methodological quality

Reference - Evid Based Complement Alternat Med 2009 Mar6(1)99 full-text

Guidelines and Resources

American College of Obstetricians and Gynecologists (ACOG) guidelines

American College of Obstetricians and Gynecologists (ACOG) Practice Bulletin 128 on diagnosis of abnormaluterinebleeding

in reproductive-aged women can be found in Obstet Gynecol 2012 Jul120(1)197 or at National Guideline Clearinghouse

2013 Feb 1138623 commentary can be found in ACOG News Release 2012 Jun 21

American College of Obstetricians and Gynecologists (ACOG) Committee Opinion 557 on management of acute

abnormaluterinebleeding in nonpregnant reproductive-aged women can be found in Obstet Gynecol 2013 Apr121(4)891

ACOG Practice Bulletin 136 on management of abnormaluterinebleeding associated with ovulatory dysfunction can be

found in Obstet Gynecol 2013 Jul122(1)176 or at National Guideline Clearinghouse 2014 Feb 1747451

ACOG Practice Bulletin 81 on endometrial ablation can be found in Obstet Gynecol 2007 May109(5)1233 reaffirmed 2012

Feb or at National Guideline Clearinghouse 2007 Dec 2410918

ACOG Committee Opinion 349 on menstruation on girls and adolescents can be found in Obstet Gynecol 2006

Nov108(5)1323 reaffirmed 2009 Jun also produced by American Academy of Pediatrics (Pediatrics 2006

Nov118(5)2245)

American College of Radiology (ACR) Appropriateness Criteria for abnormal vaginal bleeding can be found at ACR 2010 PDF or

at National Guideline Clearinghouse 2011 Sep 532629

Society of Gynecologic Surgeons (SGS) clinical practice guideline on abnormaluterinebleeding hysterectomy versus alternative

therapy can be found in J Minim Invasive Gynecol 2012 Jan-Feb19(1)81

American College of RadiologyAmerican College of Obstetricians and GynecologistsAmerican Institute of Ultrasound in Medicine

(ACRACOGAIUM) guideline on performance of sonohysterography can be found in J Ultrasound Med 2012 Jan31(1)165 full-

text or at ACRACOGAIUM 2011 PDF

National Institute for Health and Clinical Excellence (NICE) guideline on

heavy menstrual bleeding can be found in NICE 2007 JanCG44 PDF

fluid-filled thermal balloon and microwave endometrial ablation techniques for heavy menstrual bleeding can be found at

NICE 2004 AprTA78

Royal College of Obstetricians and Gynaecologists (RCOG) guideline on best practice in outpatient hysteroscopy can be found

at RCOG 2011 Mar PDF or at National Guideline Clearinghouse 2012 May 1434905

Society of Obstetricians and Gynaecologists of Canada (SOGC) guideline on abnormaluterinebleeding in pre-menopausal women

can be found at SOGC 2013 May 23 PDF or at National Guideline Clearinghouse 2014 Jan 646416

Society of Obstetricians and Gynaecologists of Canada (SOGC) clinical guideline on female sexual health consensus can be

found at SOGC 2012 PDF or at National Guideline Clearinghouse 2013 Jun 338474

Society of Obstetricians and Gynaecologists of Canada (SOGC) recommendations on asymptomatic endometrial thickening can

be found in J Obstet Gynaecol Can 2010 Oct32(10)990 PDF

Alberta Health Services (AHS) clinical practice guideline on uterine sarcoma can be found at AHS 2011 Aug PDF or at National

Guideline Clearinghouse 2013 Mar 438596

Collegravege National des Gyneacutecologues et Obsteacutetriciens Franccedilais (CNGOF) clinical practice guideline on menorrhagia management of

abnormaluterinebleeding before menopause can be found in Eur J Obstet Gynecol Reprod Biol 2010 Oct152(2)133

Mexican School of Obstetrics and Gynecology (Colegio Mexicano de Especialistas en Ginecologa y Obstetricia) clinical practice

guideline on dysfunctional uterinebleeding can be found in Ginecol Obstet Mex 2009 Sep77(9)S231 EBSCOhost Full Text

[Spanish]

review can be found in Am Fam Physician 2004 Apr 1569(8)1915

review can be found in Postgrad Med 2001 Jan109(1)137

review can be found in Am Fam Physician 1999 Oct 160(5)1371

review of managing unscheduled bleeding in non-pregnant premenopausal women can be found in BMJ 2013 Jun 4346f3251

1142014 DynaMed

httpwebbebscohostcomezproxysibdiucraccr2048dynameddeliveryprintcitationexpand=sec-General-Informationsec-Causessec-History-and-Physicahellip 1113

ICD-9 codes

ICD-10 codes

General references used

Recommendation grading systems used

AHRQ Comparative Effectiveness Review on primary care management of abnormaluterinebleeding 2013 Mar96 PDF

review of abnormaluterinebleeding in premenopausal women can be found in Am Fam Physician 2012 Jan 185(1)35

EBSCOhost Full Text

reviews of terminology controversy can be found in Fertil Steril 2008 Dec90(6)2269 Curr Opin Obstet Gynecol 2007

Dec19(6)591

review of treatment of dysfunctional uterinebleeding can be found in Maturitas 2004 Mar 1547(3)159

review of health-related quality of life work impairment and health-care costs and utilization in abnormaluterinebleeding can be

found in Value Health 2007 May-Jun10(3)183 EBSCOhost Full Text

Patient Information

handout from American College of Obstetricians and Gynecologists PDF

handout from American Society for Reproductive Medicine PDF

handout from American Academy of Family Physicians or in Spanish

handout on dysfunctional uterinebleeding from TeensHealth or in Spanish

technical information on dysfunctional uterinebleeding from Patient Plus PDF

handout on reasons for problem bleeding from Cleveland Clinic

handout on vaginal bleeding from Mayo Clinic

handout on dysfunctional uterinebleeding questions to discuss with your doctor from Harvard Medical School

ICD-9ICD-10 Codes

6262 excessive or frequent menstruation

6263 puberty bleeding

6264 irregular menstrual cycle

6265 ovulation bleeding

6266 metrorrhagia

6267 postcoital bleeding

6268 other disorders of menstruation and other abnormalbleeding from female genital tract

6269 unspecified disorders of menstruation and other abnormalbleeding from female genital tract

N92 excessive frequent and irregular menstruation

N920 excessive and frequent menstruation with regular cycle

N921 excessive and frequent menstruation with irregular cycle

N922 excessive menstruation at puberty

N923 ovulation bleeding

N924 excessive bleeding in the premenopausal period

N925 other specified irregular menstruation

N926 irregular menstruation unspecified

N93 other abnormaluterine and vaginal bleeding

N930 postcoital and contact bleeding

N938 other specified abnormaluterine and vaginal bleeding

N939 abnormaluterine and vaginal bleeding unspecified

References

1 Ely JW Kennedy CM Clark EC Bowdler NC Abnormaluterinebleeding a management algorithm J Am Board Fam Med

2006 Nov-Dec19(6)590-602 full-text

2 Casablanca Y Management of dysfunctional uterinebleeding Obstet Gynecol Clin North Am 2008 Jun35(2)219-34 viii

3 Amann M Anguino H Bauman RA et al Chronic abnormaluterinebleeding in nongravid women Pasadena (CA) Kaiser

Permanente Southern California National Guideline Clearinghouse 2007 Oct 2910889

4 National Collaborating Centre for Womenrsquos and Childrenrsquos Health Heavy menstrual bleeding National Institute for Health and

Clinical Excellence (NICE) 2007 JanCG44 PDF

Kaiser Permanente Southern California uses American College of Obstetricians and Gynecologists (ACOG) strength of

recommendation classification

grades of recommendation

Level A - based on good and consistent scientific evidence

1142014 DynaMed

httpwebbebscohostcomezproxysibdiucraccr2048dynameddeliveryprintcitationexpand=sec-General-Informationsec-Causessec-History-and-Physicahellip 1213

DynaMed editorial process

Special acknowledgements

How to cite

Level B - based on limited or inconsistent scientific evidence

Level C - based primarily on consensus and expert opinion

Reference - Kaiser Permanente Southern California guideline on chronic abnormaluterinebleeding in nongravid women

(National Guideline Clearinghouse 2007 Oct 2910889)

National Institute for Health and Clinical Excellence (NICE) grading system for recommendations

Grade A

at least 1 meta-analysis systematic review or randomized controlled trial (RCT) that is rated 1++ and is directly

applicable to target population or

systematic review of RCTs or body of evidence that consists principally of studies rated 1+ is directly applicable to

target population and demonstrates overall consistency of results or

evidence drawn from NICE technology appraisal

Grade B

body of evidence that includes studies rated 2++ is directly applicable to target population and demonstrates overall

consistency of results or

extrapolated evidence from studies rated 1++ or 1+

Grade C

body of evidence that includes studies rated 2++ is directly applicable to target population and demonstrates overall

consistency of results or

extrapolated evidence from studies rated 2++

Grade D

evidence level 3 or 4 or

extrapolated evidence from studies rated 2+ or

formal consensus

Grade D (GPP) - a good practice point (GPP) is a recommendation for best practice based on experience of Guideline

Development Group

levels of evidence for intervention studies

1++ includes high-quality meta-analyses systematic reviews of RCTs or RCTs with very low risk of bias

1+ includes well-conducted meta-analyses systematic reviews of RCTs or RCTs with low risk of bias

1- includes meta-analyses systematic reviews of RCTs or RCTs with high risk of bias

2++ includes high-quality systematic reviews of case-control or cohort studies high-quality case-control or cohort

studies with very low risk of confounding bias or chance and high probability relationship is casual

2+ includes well-conducted case-control or cohort studies with low risk of confounding bias or chance and moderate

probability relationship is casual

2- includes case-control or cohort studies with high risk of confounding bias or chance and significant risk relationship is

not casual

3 includes nonanalytical studies (for example case reports case series)

4 includes expert opinion formal consensus

Reference - NICE guideline on heavy menstrual bleeding (NICE 2007 JanCG44 PDF)

DynaMed topics are created and maintained by the DynaMed Editorial Team

Over 500 journals and evidence-based sources (DynaMed Content Sources) are monitored directly or indirectly using a 7-Step

evidence-based method for systematic literature surveillance DynaMed topics are updated daily as newly discovered best

available evidence is identified

The participating members of the DynaMed Editorial Team have declared that they have no financial or other competing

interests related to this topic

The participating reviewers have declared that they have no financial or other competing interests related to this topic unless

otherwise indicated

McMaster University is a partner that provides support in identifying Practice-Changing DynaMed Updates Over 1000 practicing

physicians from 61 disciplines in 77 countries rate these articles to help you find the most useful new evidence affecting your

practice

F1000 is a partner that provides support in identifying Practice-Changing DynaMed Updates Over 2000 practicing clinicians from

20 disciplines in 60 countries rate these articles to help you find the most useful new evidence affecting your practice

Linda Feng Chang PharmD MPH BCPS (EPC Course Director and Clinical Assistant Professor of Pharmacy University of Illinois

College of Medicine Illinois United States) provides peer review

1142014 DynaMed

httpwebbebscohostcomezproxysibdiucraccr2048dynameddeliveryprintcitationexpand=sec-General-Informationsec-Causessec-History-and-Physicahellip 1313

Estaacute viendo un resumen de DynaMed El uso de DynaMed indica la aceptacioacuten de las DynaMed Condiciones de uso Las limitaciones de

DynaMed se encuentran en las Condiciones de uso de DynaMed

Haga sus comentarios enviando un correo electroacutenico para DynaMed a DynaMedEditorebscohostcom

For attribution in other publications see How to Cite Information from DynaMed

Parte superior de la paacutegina Sitio de asistencia de EBSCO Claacuteusula de confidencialidad Teacuterminos de uso Copyright

copy 2014 EBSCO Industries Inc Todos los derechos reservados

Page 10: Abnormal uterine bleeding - AEEMmedicina-ucr.com/.../2014/04/Abnormal-Uterine-Bleeding-DynaMed.pdf · Abnormal uterine bleeding ... endometrial ablation preferable to hysterectomy

1142014 DynaMed

httpwebbebscohostcomezproxysibdiucraccr2048dynameddeliveryprintcitationexpand=sec-General-Informationsec-Causessec-History-and-Physicahellip 1013

Guidelines

United States guidelines

United Kingdom guidelines

Canadian guidelines

European guidelines

Mexican guidelines

Review articles

based on meta-analysis

all except one trial had poor methodological quality

Reference - Evid Based Complement Alternat Med 2009 Mar6(1)99 full-text

Guidelines and Resources

American College of Obstetricians and Gynecologists (ACOG) guidelines

American College of Obstetricians and Gynecologists (ACOG) Practice Bulletin 128 on diagnosis of abnormaluterinebleeding

in reproductive-aged women can be found in Obstet Gynecol 2012 Jul120(1)197 or at National Guideline Clearinghouse

2013 Feb 1138623 commentary can be found in ACOG News Release 2012 Jun 21

American College of Obstetricians and Gynecologists (ACOG) Committee Opinion 557 on management of acute

abnormaluterinebleeding in nonpregnant reproductive-aged women can be found in Obstet Gynecol 2013 Apr121(4)891

ACOG Practice Bulletin 136 on management of abnormaluterinebleeding associated with ovulatory dysfunction can be

found in Obstet Gynecol 2013 Jul122(1)176 or at National Guideline Clearinghouse 2014 Feb 1747451

ACOG Practice Bulletin 81 on endometrial ablation can be found in Obstet Gynecol 2007 May109(5)1233 reaffirmed 2012

Feb or at National Guideline Clearinghouse 2007 Dec 2410918

ACOG Committee Opinion 349 on menstruation on girls and adolescents can be found in Obstet Gynecol 2006

Nov108(5)1323 reaffirmed 2009 Jun also produced by American Academy of Pediatrics (Pediatrics 2006

Nov118(5)2245)

American College of Radiology (ACR) Appropriateness Criteria for abnormal vaginal bleeding can be found at ACR 2010 PDF or

at National Guideline Clearinghouse 2011 Sep 532629

Society of Gynecologic Surgeons (SGS) clinical practice guideline on abnormaluterinebleeding hysterectomy versus alternative

therapy can be found in J Minim Invasive Gynecol 2012 Jan-Feb19(1)81

American College of RadiologyAmerican College of Obstetricians and GynecologistsAmerican Institute of Ultrasound in Medicine

(ACRACOGAIUM) guideline on performance of sonohysterography can be found in J Ultrasound Med 2012 Jan31(1)165 full-

text or at ACRACOGAIUM 2011 PDF

National Institute for Health and Clinical Excellence (NICE) guideline on

heavy menstrual bleeding can be found in NICE 2007 JanCG44 PDF

fluid-filled thermal balloon and microwave endometrial ablation techniques for heavy menstrual bleeding can be found at

NICE 2004 AprTA78

Royal College of Obstetricians and Gynaecologists (RCOG) guideline on best practice in outpatient hysteroscopy can be found

at RCOG 2011 Mar PDF or at National Guideline Clearinghouse 2012 May 1434905

Society of Obstetricians and Gynaecologists of Canada (SOGC) guideline on abnormaluterinebleeding in pre-menopausal women

can be found at SOGC 2013 May 23 PDF or at National Guideline Clearinghouse 2014 Jan 646416

Society of Obstetricians and Gynaecologists of Canada (SOGC) clinical guideline on female sexual health consensus can be

found at SOGC 2012 PDF or at National Guideline Clearinghouse 2013 Jun 338474

Society of Obstetricians and Gynaecologists of Canada (SOGC) recommendations on asymptomatic endometrial thickening can

be found in J Obstet Gynaecol Can 2010 Oct32(10)990 PDF

Alberta Health Services (AHS) clinical practice guideline on uterine sarcoma can be found at AHS 2011 Aug PDF or at National

Guideline Clearinghouse 2013 Mar 438596

Collegravege National des Gyneacutecologues et Obsteacutetriciens Franccedilais (CNGOF) clinical practice guideline on menorrhagia management of

abnormaluterinebleeding before menopause can be found in Eur J Obstet Gynecol Reprod Biol 2010 Oct152(2)133

Mexican School of Obstetrics and Gynecology (Colegio Mexicano de Especialistas en Ginecologa y Obstetricia) clinical practice

guideline on dysfunctional uterinebleeding can be found in Ginecol Obstet Mex 2009 Sep77(9)S231 EBSCOhost Full Text

[Spanish]

review can be found in Am Fam Physician 2004 Apr 1569(8)1915

review can be found in Postgrad Med 2001 Jan109(1)137

review can be found in Am Fam Physician 1999 Oct 160(5)1371

review of managing unscheduled bleeding in non-pregnant premenopausal women can be found in BMJ 2013 Jun 4346f3251

1142014 DynaMed

httpwebbebscohostcomezproxysibdiucraccr2048dynameddeliveryprintcitationexpand=sec-General-Informationsec-Causessec-History-and-Physicahellip 1113

ICD-9 codes

ICD-10 codes

General references used

Recommendation grading systems used

AHRQ Comparative Effectiveness Review on primary care management of abnormaluterinebleeding 2013 Mar96 PDF

review of abnormaluterinebleeding in premenopausal women can be found in Am Fam Physician 2012 Jan 185(1)35

EBSCOhost Full Text

reviews of terminology controversy can be found in Fertil Steril 2008 Dec90(6)2269 Curr Opin Obstet Gynecol 2007

Dec19(6)591

review of treatment of dysfunctional uterinebleeding can be found in Maturitas 2004 Mar 1547(3)159

review of health-related quality of life work impairment and health-care costs and utilization in abnormaluterinebleeding can be

found in Value Health 2007 May-Jun10(3)183 EBSCOhost Full Text

Patient Information

handout from American College of Obstetricians and Gynecologists PDF

handout from American Society for Reproductive Medicine PDF

handout from American Academy of Family Physicians or in Spanish

handout on dysfunctional uterinebleeding from TeensHealth or in Spanish

technical information on dysfunctional uterinebleeding from Patient Plus PDF

handout on reasons for problem bleeding from Cleveland Clinic

handout on vaginal bleeding from Mayo Clinic

handout on dysfunctional uterinebleeding questions to discuss with your doctor from Harvard Medical School

ICD-9ICD-10 Codes

6262 excessive or frequent menstruation

6263 puberty bleeding

6264 irregular menstrual cycle

6265 ovulation bleeding

6266 metrorrhagia

6267 postcoital bleeding

6268 other disorders of menstruation and other abnormalbleeding from female genital tract

6269 unspecified disorders of menstruation and other abnormalbleeding from female genital tract

N92 excessive frequent and irregular menstruation

N920 excessive and frequent menstruation with regular cycle

N921 excessive and frequent menstruation with irregular cycle

N922 excessive menstruation at puberty

N923 ovulation bleeding

N924 excessive bleeding in the premenopausal period

N925 other specified irregular menstruation

N926 irregular menstruation unspecified

N93 other abnormaluterine and vaginal bleeding

N930 postcoital and contact bleeding

N938 other specified abnormaluterine and vaginal bleeding

N939 abnormaluterine and vaginal bleeding unspecified

References

1 Ely JW Kennedy CM Clark EC Bowdler NC Abnormaluterinebleeding a management algorithm J Am Board Fam Med

2006 Nov-Dec19(6)590-602 full-text

2 Casablanca Y Management of dysfunctional uterinebleeding Obstet Gynecol Clin North Am 2008 Jun35(2)219-34 viii

3 Amann M Anguino H Bauman RA et al Chronic abnormaluterinebleeding in nongravid women Pasadena (CA) Kaiser

Permanente Southern California National Guideline Clearinghouse 2007 Oct 2910889

4 National Collaborating Centre for Womenrsquos and Childrenrsquos Health Heavy menstrual bleeding National Institute for Health and

Clinical Excellence (NICE) 2007 JanCG44 PDF

Kaiser Permanente Southern California uses American College of Obstetricians and Gynecologists (ACOG) strength of

recommendation classification

grades of recommendation

Level A - based on good and consistent scientific evidence

1142014 DynaMed

httpwebbebscohostcomezproxysibdiucraccr2048dynameddeliveryprintcitationexpand=sec-General-Informationsec-Causessec-History-and-Physicahellip 1213

DynaMed editorial process

Special acknowledgements

How to cite

Level B - based on limited or inconsistent scientific evidence

Level C - based primarily on consensus and expert opinion

Reference - Kaiser Permanente Southern California guideline on chronic abnormaluterinebleeding in nongravid women

(National Guideline Clearinghouse 2007 Oct 2910889)

National Institute for Health and Clinical Excellence (NICE) grading system for recommendations

Grade A

at least 1 meta-analysis systematic review or randomized controlled trial (RCT) that is rated 1++ and is directly

applicable to target population or

systematic review of RCTs or body of evidence that consists principally of studies rated 1+ is directly applicable to

target population and demonstrates overall consistency of results or

evidence drawn from NICE technology appraisal

Grade B

body of evidence that includes studies rated 2++ is directly applicable to target population and demonstrates overall

consistency of results or

extrapolated evidence from studies rated 1++ or 1+

Grade C

body of evidence that includes studies rated 2++ is directly applicable to target population and demonstrates overall

consistency of results or

extrapolated evidence from studies rated 2++

Grade D

evidence level 3 or 4 or

extrapolated evidence from studies rated 2+ or

formal consensus

Grade D (GPP) - a good practice point (GPP) is a recommendation for best practice based on experience of Guideline

Development Group

levels of evidence for intervention studies

1++ includes high-quality meta-analyses systematic reviews of RCTs or RCTs with very low risk of bias

1+ includes well-conducted meta-analyses systematic reviews of RCTs or RCTs with low risk of bias

1- includes meta-analyses systematic reviews of RCTs or RCTs with high risk of bias

2++ includes high-quality systematic reviews of case-control or cohort studies high-quality case-control or cohort

studies with very low risk of confounding bias or chance and high probability relationship is casual

2+ includes well-conducted case-control or cohort studies with low risk of confounding bias or chance and moderate

probability relationship is casual

2- includes case-control or cohort studies with high risk of confounding bias or chance and significant risk relationship is

not casual

3 includes nonanalytical studies (for example case reports case series)

4 includes expert opinion formal consensus

Reference - NICE guideline on heavy menstrual bleeding (NICE 2007 JanCG44 PDF)

DynaMed topics are created and maintained by the DynaMed Editorial Team

Over 500 journals and evidence-based sources (DynaMed Content Sources) are monitored directly or indirectly using a 7-Step

evidence-based method for systematic literature surveillance DynaMed topics are updated daily as newly discovered best

available evidence is identified

The participating members of the DynaMed Editorial Team have declared that they have no financial or other competing

interests related to this topic

The participating reviewers have declared that they have no financial or other competing interests related to this topic unless

otherwise indicated

McMaster University is a partner that provides support in identifying Practice-Changing DynaMed Updates Over 1000 practicing

physicians from 61 disciplines in 77 countries rate these articles to help you find the most useful new evidence affecting your

practice

F1000 is a partner that provides support in identifying Practice-Changing DynaMed Updates Over 2000 practicing clinicians from

20 disciplines in 60 countries rate these articles to help you find the most useful new evidence affecting your practice

Linda Feng Chang PharmD MPH BCPS (EPC Course Director and Clinical Assistant Professor of Pharmacy University of Illinois

College of Medicine Illinois United States) provides peer review

1142014 DynaMed

httpwebbebscohostcomezproxysibdiucraccr2048dynameddeliveryprintcitationexpand=sec-General-Informationsec-Causessec-History-and-Physicahellip 1313

Estaacute viendo un resumen de DynaMed El uso de DynaMed indica la aceptacioacuten de las DynaMed Condiciones de uso Las limitaciones de

DynaMed se encuentran en las Condiciones de uso de DynaMed

Haga sus comentarios enviando un correo electroacutenico para DynaMed a DynaMedEditorebscohostcom

For attribution in other publications see How to Cite Information from DynaMed

Parte superior de la paacutegina Sitio de asistencia de EBSCO Claacuteusula de confidencialidad Teacuterminos de uso Copyright

copy 2014 EBSCO Industries Inc Todos los derechos reservados

Page 11: Abnormal uterine bleeding - AEEMmedicina-ucr.com/.../2014/04/Abnormal-Uterine-Bleeding-DynaMed.pdf · Abnormal uterine bleeding ... endometrial ablation preferable to hysterectomy

1142014 DynaMed

httpwebbebscohostcomezproxysibdiucraccr2048dynameddeliveryprintcitationexpand=sec-General-Informationsec-Causessec-History-and-Physicahellip 1113

ICD-9 codes

ICD-10 codes

General references used

Recommendation grading systems used

AHRQ Comparative Effectiveness Review on primary care management of abnormaluterinebleeding 2013 Mar96 PDF

review of abnormaluterinebleeding in premenopausal women can be found in Am Fam Physician 2012 Jan 185(1)35

EBSCOhost Full Text

reviews of terminology controversy can be found in Fertil Steril 2008 Dec90(6)2269 Curr Opin Obstet Gynecol 2007

Dec19(6)591

review of treatment of dysfunctional uterinebleeding can be found in Maturitas 2004 Mar 1547(3)159

review of health-related quality of life work impairment and health-care costs and utilization in abnormaluterinebleeding can be

found in Value Health 2007 May-Jun10(3)183 EBSCOhost Full Text

Patient Information

handout from American College of Obstetricians and Gynecologists PDF

handout from American Society for Reproductive Medicine PDF

handout from American Academy of Family Physicians or in Spanish

handout on dysfunctional uterinebleeding from TeensHealth or in Spanish

technical information on dysfunctional uterinebleeding from Patient Plus PDF

handout on reasons for problem bleeding from Cleveland Clinic

handout on vaginal bleeding from Mayo Clinic

handout on dysfunctional uterinebleeding questions to discuss with your doctor from Harvard Medical School

ICD-9ICD-10 Codes

6262 excessive or frequent menstruation

6263 puberty bleeding

6264 irregular menstrual cycle

6265 ovulation bleeding

6266 metrorrhagia

6267 postcoital bleeding

6268 other disorders of menstruation and other abnormalbleeding from female genital tract

6269 unspecified disorders of menstruation and other abnormalbleeding from female genital tract

N92 excessive frequent and irregular menstruation

N920 excessive and frequent menstruation with regular cycle

N921 excessive and frequent menstruation with irregular cycle

N922 excessive menstruation at puberty

N923 ovulation bleeding

N924 excessive bleeding in the premenopausal period

N925 other specified irregular menstruation

N926 irregular menstruation unspecified

N93 other abnormaluterine and vaginal bleeding

N930 postcoital and contact bleeding

N938 other specified abnormaluterine and vaginal bleeding

N939 abnormaluterine and vaginal bleeding unspecified

References

1 Ely JW Kennedy CM Clark EC Bowdler NC Abnormaluterinebleeding a management algorithm J Am Board Fam Med

2006 Nov-Dec19(6)590-602 full-text

2 Casablanca Y Management of dysfunctional uterinebleeding Obstet Gynecol Clin North Am 2008 Jun35(2)219-34 viii

3 Amann M Anguino H Bauman RA et al Chronic abnormaluterinebleeding in nongravid women Pasadena (CA) Kaiser

Permanente Southern California National Guideline Clearinghouse 2007 Oct 2910889

4 National Collaborating Centre for Womenrsquos and Childrenrsquos Health Heavy menstrual bleeding National Institute for Health and

Clinical Excellence (NICE) 2007 JanCG44 PDF

Kaiser Permanente Southern California uses American College of Obstetricians and Gynecologists (ACOG) strength of

recommendation classification

grades of recommendation

Level A - based on good and consistent scientific evidence

1142014 DynaMed

httpwebbebscohostcomezproxysibdiucraccr2048dynameddeliveryprintcitationexpand=sec-General-Informationsec-Causessec-History-and-Physicahellip 1213

DynaMed editorial process

Special acknowledgements

How to cite

Level B - based on limited or inconsistent scientific evidence

Level C - based primarily on consensus and expert opinion

Reference - Kaiser Permanente Southern California guideline on chronic abnormaluterinebleeding in nongravid women

(National Guideline Clearinghouse 2007 Oct 2910889)

National Institute for Health and Clinical Excellence (NICE) grading system for recommendations

Grade A

at least 1 meta-analysis systematic review or randomized controlled trial (RCT) that is rated 1++ and is directly

applicable to target population or

systematic review of RCTs or body of evidence that consists principally of studies rated 1+ is directly applicable to

target population and demonstrates overall consistency of results or

evidence drawn from NICE technology appraisal

Grade B

body of evidence that includes studies rated 2++ is directly applicable to target population and demonstrates overall

consistency of results or

extrapolated evidence from studies rated 1++ or 1+

Grade C

body of evidence that includes studies rated 2++ is directly applicable to target population and demonstrates overall

consistency of results or

extrapolated evidence from studies rated 2++

Grade D

evidence level 3 or 4 or

extrapolated evidence from studies rated 2+ or

formal consensus

Grade D (GPP) - a good practice point (GPP) is a recommendation for best practice based on experience of Guideline

Development Group

levels of evidence for intervention studies

1++ includes high-quality meta-analyses systematic reviews of RCTs or RCTs with very low risk of bias

1+ includes well-conducted meta-analyses systematic reviews of RCTs or RCTs with low risk of bias

1- includes meta-analyses systematic reviews of RCTs or RCTs with high risk of bias

2++ includes high-quality systematic reviews of case-control or cohort studies high-quality case-control or cohort

studies with very low risk of confounding bias or chance and high probability relationship is casual

2+ includes well-conducted case-control or cohort studies with low risk of confounding bias or chance and moderate

probability relationship is casual

2- includes case-control or cohort studies with high risk of confounding bias or chance and significant risk relationship is

not casual

3 includes nonanalytical studies (for example case reports case series)

4 includes expert opinion formal consensus

Reference - NICE guideline on heavy menstrual bleeding (NICE 2007 JanCG44 PDF)

DynaMed topics are created and maintained by the DynaMed Editorial Team

Over 500 journals and evidence-based sources (DynaMed Content Sources) are monitored directly or indirectly using a 7-Step

evidence-based method for systematic literature surveillance DynaMed topics are updated daily as newly discovered best

available evidence is identified

The participating members of the DynaMed Editorial Team have declared that they have no financial or other competing

interests related to this topic

The participating reviewers have declared that they have no financial or other competing interests related to this topic unless

otherwise indicated

McMaster University is a partner that provides support in identifying Practice-Changing DynaMed Updates Over 1000 practicing

physicians from 61 disciplines in 77 countries rate these articles to help you find the most useful new evidence affecting your

practice

F1000 is a partner that provides support in identifying Practice-Changing DynaMed Updates Over 2000 practicing clinicians from

20 disciplines in 60 countries rate these articles to help you find the most useful new evidence affecting your practice

Linda Feng Chang PharmD MPH BCPS (EPC Course Director and Clinical Assistant Professor of Pharmacy University of Illinois

College of Medicine Illinois United States) provides peer review

1142014 DynaMed

httpwebbebscohostcomezproxysibdiucraccr2048dynameddeliveryprintcitationexpand=sec-General-Informationsec-Causessec-History-and-Physicahellip 1313

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DynaMed editorial process

Special acknowledgements

How to cite

Level B - based on limited or inconsistent scientific evidence

Level C - based primarily on consensus and expert opinion

Reference - Kaiser Permanente Southern California guideline on chronic abnormaluterinebleeding in nongravid women

(National Guideline Clearinghouse 2007 Oct 2910889)

National Institute for Health and Clinical Excellence (NICE) grading system for recommendations

Grade A

at least 1 meta-analysis systematic review or randomized controlled trial (RCT) that is rated 1++ and is directly

applicable to target population or

systematic review of RCTs or body of evidence that consists principally of studies rated 1+ is directly applicable to

target population and demonstrates overall consistency of results or

evidence drawn from NICE technology appraisal

Grade B

body of evidence that includes studies rated 2++ is directly applicable to target population and demonstrates overall

consistency of results or

extrapolated evidence from studies rated 1++ or 1+

Grade C

body of evidence that includes studies rated 2++ is directly applicable to target population and demonstrates overall

consistency of results or

extrapolated evidence from studies rated 2++

Grade D

evidence level 3 or 4 or

extrapolated evidence from studies rated 2+ or

formal consensus

Grade D (GPP) - a good practice point (GPP) is a recommendation for best practice based on experience of Guideline

Development Group

levels of evidence for intervention studies

1++ includes high-quality meta-analyses systematic reviews of RCTs or RCTs with very low risk of bias

1+ includes well-conducted meta-analyses systematic reviews of RCTs or RCTs with low risk of bias

1- includes meta-analyses systematic reviews of RCTs or RCTs with high risk of bias

2++ includes high-quality systematic reviews of case-control or cohort studies high-quality case-control or cohort

studies with very low risk of confounding bias or chance and high probability relationship is casual

2+ includes well-conducted case-control or cohort studies with low risk of confounding bias or chance and moderate

probability relationship is casual

2- includes case-control or cohort studies with high risk of confounding bias or chance and significant risk relationship is

not casual

3 includes nonanalytical studies (for example case reports case series)

4 includes expert opinion formal consensus

Reference - NICE guideline on heavy menstrual bleeding (NICE 2007 JanCG44 PDF)

DynaMed topics are created and maintained by the DynaMed Editorial Team

Over 500 journals and evidence-based sources (DynaMed Content Sources) are monitored directly or indirectly using a 7-Step

evidence-based method for systematic literature surveillance DynaMed topics are updated daily as newly discovered best

available evidence is identified

The participating members of the DynaMed Editorial Team have declared that they have no financial or other competing

interests related to this topic

The participating reviewers have declared that they have no financial or other competing interests related to this topic unless

otherwise indicated

McMaster University is a partner that provides support in identifying Practice-Changing DynaMed Updates Over 1000 practicing

physicians from 61 disciplines in 77 countries rate these articles to help you find the most useful new evidence affecting your

practice

F1000 is a partner that provides support in identifying Practice-Changing DynaMed Updates Over 2000 practicing clinicians from

20 disciplines in 60 countries rate these articles to help you find the most useful new evidence affecting your practice

Linda Feng Chang PharmD MPH BCPS (EPC Course Director and Clinical Assistant Professor of Pharmacy University of Illinois

College of Medicine Illinois United States) provides peer review

1142014 DynaMed

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Estaacute viendo un resumen de DynaMed El uso de DynaMed indica la aceptacioacuten de las DynaMed Condiciones de uso Las limitaciones de

DynaMed se encuentran en las Condiciones de uso de DynaMed

Haga sus comentarios enviando un correo electroacutenico para DynaMed a DynaMedEditorebscohostcom

For attribution in other publications see How to Cite Information from DynaMed

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Estaacute viendo un resumen de DynaMed El uso de DynaMed indica la aceptacioacuten de las DynaMed Condiciones de uso Las limitaciones de

DynaMed se encuentran en las Condiciones de uso de DynaMed

Haga sus comentarios enviando un correo electroacutenico para DynaMed a DynaMedEditorebscohostcom

For attribution in other publications see How to Cite Information from DynaMed

Parte superior de la paacutegina Sitio de asistencia de EBSCO Claacuteusula de confidencialidad Teacuterminos de uso Copyright

copy 2014 EBSCO Industries Inc Todos los derechos reservados