Perimenopausal bleeding

Perimenopausal bleeding controversies and consensus

Perimenopausal bleeding

comprehensive evaluation to save uterus.Veerendrakumar CM MD.,DNBProfessorDept of OBG,VIMS,Bellary.12/11/20131Prof.Veerendrakumar, VIMS, Bellary.

READ/LISTEN/TALK toNot to contradict & Confute.Nor to believe & take it for granted.Nor to find & discourse.But to weigh & consider. Francis Bacon12/11/20132Prof.Veerendrakumar, VIMS, Bellary.

Litigant and evidence based world..Dont simply knock off the uterus.Uterus is a marker of FEMINITY.Make all efforts to save it

Comprehensive evaluation can offer specific treatment.

12/11/2013Prof.Veerendrakumar, VIMS, Bellary. 3

Perimenopausal bleedingIt is 3-5 years period before menopause with increase frequent irregular anovulatory bleeding followed by episodes of ammenorrhea and intermittent menopausal symptoms.

12/11/20134Prof.Veerendrakumar, VIMS, Bellary.

low resource basic investigations for abnormal uterine bleeding (AUB)

bearing in mind issues of effectiveness and cost effectiveness.12/11/20135Prof.Veerendrakumar, VIMS, Bellary.

Ideally, the evaluation is comprehensive, considering each of the potential etiological domains as defined by FIGO

PALM-COEIN system for Causes.

International Journal of Gynecology and Obstetrics 113 (2011) 31312/11/20136Prof.Veerendrakumar, VIMS, Bellary.

Figo classification of causes of AUB


the extent of investigations will be significantly influenced by the

technologies available and the time allotted for a consultation.12/11/20138Prof.Veerendrakumar, VIMS, Bellary.

investigations should be performed only if they will make a material difference to the management approaches that can be offered. 12/11/20139Prof.Veerendrakumar, VIMS, Bellary.

AUBheavy menstrual bleeding (HMB), intermenstrual bleeding (IMB), and irregular menstrual bleeding are very common.

Semin Reprod Med 2011;29(5):38339012/11/201310Prof.Veerendrakumar, VIMS, Bellary.

Medications that can be associated with abnormal uterine bleedingAnticoagulantsAntidepressants (SSRIand tricyclics)Hormonal contraceptivesTamoxifenAntipsychoticsCorticosteroids Herbs: ginseng,chasteberry,danshen


Systematic investigation

Determination of the clinical impact of the symptom with HMB

Evaluation of the patient for the underlying cause12/11/201312Prof.Veerendrakumar, VIMS, Bellary.

Assesmeent of blood loss..Frequency of changing "menstrual protection" items, use of "double" protection;changing menstrual protection at night; self-consciousness about odor; inability to contain "gushes" of menstrualflow; embarrassment at being unable to contain "gushes" of flow, and preparations and rituals to prevent embarrassing episodes.

NICE Guideline 44; Heavy menstrual bleeding.Women Health 2010;50(2): 195211


Pelvic examinationpelvic signs are picked up with low sensitivity and specificity in most situations, especially when influenced by obesity and the nervous patient.

postgraduate training improves the accuracy of this examination,

Int J Gynaecol Obstet 2005;88(1):8488it is of great value in the evaluation of the cervix.12/11/201314Prof.Veerendrakumar, VIMS, Bellary.

Labortatory assesmentEvaluation for coagulopathies that may contribute to HMB (AUB-C) is important in any setting

Ann Hematol 2005;84(5):339342Fertil Steril 2005;84(5):1345135112/11/201315Prof.Veerendrakumar, VIMS, Bellary.

Acquire knowledge and clinical skills to Comprehensively evaluate the uterus

1. assessment of the endometrium for the presence of hyperplasia or malignancy;

2.visualization of the endometrial cavity and cervical canal for localized Lesions and

3.evaluation of the structure of the uterine wall for adenomyosis, leiomyomas, and,

more rarely, arteriovenous malformations.

Semin Reprod Med 2011;29(5):39139912/11/201316Prof.Veerendrakumar, VIMS, Bellary.

Ultrasound TVUS is undoubtedly the primary imaging modality

highly dependent on the skill and experience of the ultrasound operator and contemporary machine !!!


TVUSan excellent tool for the determination of whether further investigation with curettage or some form of endometrial biopsy is necessary

Am J Obstet Gynecol.2003 Feb;188(2):401-8.


Typically, endometrial thickness is actually measured and reported as the sum of the two adjacent layers of endometrium, in essence a double thickness, a measurement called

the Endometrial Echo Complex, or EEC.


as long as the EEC thickness is 12 mm (in premenopausal women), there is a very low incidence ofendometrial hyperplasia or neoplasia.

Ultrasound Obstet Gynecol 1998;11(5):33734212/11/201320Prof.Veerendrakumar, VIMS, Bellary.

Who should undergo endometrial sampling?AUB and an EEC >12 mm should be sampled.age >45 years; obesity (>90 kg) a history of chronic anovulation, infertility, or diabetes; a family history of endometrial cancer; andprolonged exposure to unopposed estrogens or tamoxifen. Am J Obstet Gynecol 1999;181(3):525529

Colorectal cancer affected families with AUB regardless of age


Endometrial samplingHistological assessment of the endometrium requires a biopsy or curettage to evaluate for endometrial hyperplasia or malignancy (AUB-M). 12/11/201322Prof.Veerendrakumar, VIMS, Bellary.

Office endometrial sampling has a reasonably high accuracy and detects 67 to 96% of endometrial carcinomas.

J Reprod Med 1995;40(8):553555


insufficient tissue obtained for diagnosis has been reported in 4 to 20% of cases.

Gynecol Obstet Invest 1994;37(4):26026212/11/201324Prof.Veerendrakumar, VIMS, Bellary.

D and C left to Oblivion ???


Rcamier's operation ( D &C )named after French gynecologist who designed curette.


Options12/11/201327Prof.Veerendrakumar, VIMS, Bellary.

Dilatation and curettage alone should not be used as a diagnostic tool.

suggested that D&C does not give additional diagnostic information over and above a hysteroscopy with endometrial biopsy and it is not therapeutic in cases of heavy menstrual bleeding

NICE clinical guideline 44 Heavy menstrual bleeding


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D&C should no longer be used as the first-line method of investigating PMB in most cases.

Scottish Intercollegiate Guidelines 201112/11/201329Prof.Veerendrakumar, VIMS, Bellary.

it is limited in its ability to access the tubal cornua of the uterus.

Hysteroscopy with biopsy provides more information than dilatation and curettage alone and rivals the combination of saline-infusion sonohysterography and endometrial biopsy in its ability to diagnose polyps, submucous fibroids, and other sources of abnormal uterine bleeding.

Am Fam Physician.2004Apr15;69(8):1915-1926.


Hysteroscopy with directed biopsy is more sensitive in disclosing all types of uterine lesions than dilatation and curettage.

Curettage done after hysteroscopy and directed biopsy does not improve the detection of endometrial cancer

Eur J Gynaecol Oncol.2007;28(5):400-2.


We support hysteroscopy as a routine alternative to dilatation and curettage in the diagnosis of postmenopausal bleeding

J Obstet Gynaecol.2001 Jan;21(1):67-9



D&C missed 58% (25/43) of polyps, 50% (5/10) of hyperplasias, 60% (3/5) of complex atypical Hyperplasias, and 11% (2/19) of endometrial cancers.


The limitations of D&C are due to the blindness of the sampling procedure.

George Vorgias,etal 10/14/2003; Medscape General Medicine. 003;5(4)


dilatation a

YOU SHOULD NOT BE OFFERED

oral progestogens for use only in the second half of your menstrual cycle

drugs called danazol and etamsylate

D and C, which involves scraping out the womb lining as a treatment or test on its own


Endometrial Biopsy (EMB) Safe, simple office procedure


Both EB and D& C ineffective at diagnosing focal lesions. Polyps (AUB-P) are frequently missed (up to 50%) by blind techniques, which may include cases of focal atypical hyperplasia and carcinoma especially in premenopausal cases.

Cancer 2000;89(8):17651772


Structural abnormalitiesP PolypA-AdenomyosisL-LeiomyomaM-Malignancy- endometrial hyperplasia and endometrial carcinoma.12/11/201339Prof.Veerendrakumar, VIMS, Bellary.

advanced TVUS developments have improved our ability to detect and define certain structural lesions.

-saline infusion sonography (SIS), -color-flow Doppler assessment, and-3D imaging techniques.12/11/201340Prof.Veerendrakumar, VIMS, Bellary.

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Endometrial Polyp3D Ultrasound12/11/201341Prof.Veerendrakumar, VIMS, Bellary.

Saline infusion sonogram (SIS)Sonohysterography.Hysterosonography, Transvaginal sonography (TVS) with fluid contrast augmentationSaline infusion sonogram (SIS)

Parson, J Clin Ultrasound 1993 Goldstein J Ultrasound Med 2001;12/11/201342Prof.Veerendrakumar, VIMS, Bellary.

SISPerformed during proliferative phaseNot later than 10 daysPost menopuasal bleeding any timeWomen on HRT time it during withdrawal or during progesterone phaseBleeding not a contraindication but clot can make interpretation difficult. But doppler can differentiate cavitory lesions.

standard for the performance of saline infusion sonohysterography. J Ultrasound Med 200312/11/201343Prof.Veerendrakumar, VIMS, Bellary.

SISIf a focal lesion is identified on SIS, that lesion can be treated with hysteroscopy. Those patients who do not have a focal lesion can be spared hysteroscopy in many cases.12/11/201344Prof.Veerendrakumar, VIMS, Bellary.

meta-analysis of 5892 women.Using a double-wall thickness of 5 mm,the sensitivity for detecting endometrial cancer was 96%

A thin endometrium of 5 mm or less had a high negative predictive value, and this finding would support the diagnosis of atrophy

JAMA 1998; 280:15101517.12/11/201345Prof.Veerendrakumar, VIMS, Bellary.

Pipelle curette is excellent for detecting endometrial processes when the pathology is global in nature. When a focal lesion is detected a visually directed biopsy is indicated.

J Reprod Med 1995; 40:553555.12/11/201346Prof.Veerendrakumar, VIMS, Bellary.

In postmenopausal women, polyps are found to be the cause of bleeding in approximately 30% of cases.

Most of these polyps are benign. malignancy in polyps ranges from 0.5% to 1.5%.Eur J Gynaecol Oncol 2000; 21:180183.12/11/201347Prof.Veerendrakumar, VIMS, Bellary.

Transvaginal sonography cannot distinguish endometrial hyperplasia from benign polyps

both conditions can cause thickening of the endometrium, are hyperechoic, and can contain cystic spaces.12/11/201348Prof.Veerendrakumar, VIMS, Bellary.

Saline infusion sonohysterography

can distinguish focal lesions from diffuse endometrial thickening. Polyps are focal lesions, which project into the lumen of the endometrial cavity12/11/201349Prof.Veerendrakumar, VIMS, Bellary.

Normal endometrium


Endometrial polyp


Multiple polyps

Longitudinal sectionTransverse section12/11/201352Prof.Veerendrakumar, VIMS, Bellary.

Sub mucous fibroid & polyp


Blood clot in the cavity

After dislodging with the catheter12/11/201354Prof.Veerendrakumar, VIMS, Bellary.

If the fibroid projects into the lumen by more than 50% of its surface, then it can be resected by hysteroscopy, obviating an abdominal surgical procedure


Endometrial hyperplasia


SIS for monitoring the pts on Tamoxifen

the finding of a normal endometrium on SIS allowed these patients to avoid further intervention.

Am J Roentgenol 1997; 168:657661.12/11/201357Prof.Veerendrakumar, VIMS, Bellary.

Future directionEndometrial biopsy with real time usg guidance

Dubinsky AJR Am J Roentgenol 200012/11/201358Prof.Veerendrakumar, VIMS, Bellary.

SISSaline infusion sonohysterography is a simple technique that yields additional information over TVS in evaluation of endometrial and subendometrial conditions.12/11/201359Prof.Veerendrakumar, VIMS, Bellary.

Clinical impact SIS added certainty to the diagnosis in 88% of the patients studied. SIS results changed the patients treatment in 80% of cases. increased diagnostic confidence by 86%.

Radiology 2000; 216:260264.12/11/201360Prof.Veerendrakumar, VIMS, Bellary.

hysteroscopyIn the presence of an abnormally thick endometrium, when myomas exist suspiciously close to the EEC or when abnormal bleeding occurs or persists despite a normal TVUS, hysteroscopy is indicated.12/11/201361Prof.Veerendrakumar, VIMS, Bellary.

Endometrial carcinoma and endometrial hyperplasia (AUB-M), especially those arising as a field defect, may not always be clearly recognizable by hysteroscope alone, which should be performed in conjunction with endometrial biopsy.

Am J Obstet Gynecol 2007;196(3):243; e1-e5


SIS v/s HysteroscopySIS is comparable to hysteroscopy in its sensitivity for the diagnosis of intracavitary polyps and submucosal myomas In SIS- limited evaluation of the endocervical canal and the inability to concurrently remove selected lesions

Fertil Steril 2010;94(7):2720272512/11/201363Prof.Veerendrakumar, VIMS, Bellary.

One stop clinic..Office hysteroscopy may be more cumbersome, involves a steeper learning curve than either TVUS or SIS, and may also be more uncomfortable for the patient.

likely to achieve a primary diagnostic role if narrow, rigid, or flexible scopes are used without anesthesia or only with local cervical anesthesia and with low-pressure saline distension in an "office" situation

Clinical practice guidelines..Eur J Obstet Gynecol Reprod Biol 2010;12/11/201364Prof.Veerendrakumar, VIMS, Bellary.

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Low resource settings..

When TVUS (including SIS) and hysteroscopy are available, it is recommended they be used in complementary fashion. In this way, hysteroscopy can be used more selectively to exploit its use as a therapeutic tool for the performance of targeted biopsy, polypectomy, or myomectomy.12/11/201365Prof.Veerendrakumar, VIMS, Bellary.





Myometrial evaluationTVUS is generally useful for the evaluation of myomas, 3 D may give additional information. TVUS is quite sensitive for the diagnosis of diffuse adenomyosis.Color flow Doppler is of value for the detection ofarteriovenous malformations ,vascular hyperplasias and malignancies. And focal adenomyosis.


Therapy Once malignancy and significant pelvic pathology have been ruled out, medical treatment is an effective first-line therapeutic option for abnormal uterine bleeding. 12/11/201371Prof.Veerendrakumar, VIMS, Bellary.

NSAIDreduced menstrual blood loss by 33% to 55% when compared with placebo, without a significant difference in adverse effects. added benefit of improving dysmenorrhea for up to 70% of patients.START before the day of menses and continue for 3-5 days. Cochrane Database Syst Rev 2007;12/11/201372Prof.Veerendrakumar, VIMS, Bellary.

Tranexemic acidoverall reduction in menstrual blood loss between 40% and 59% from baseline.1 gram of tranexamic acid taken orally every 6 hours during menstruation, but a single daily dose of 4 grams has also been found to be effectiveIntravenous tranexamic acid is available for more acute scenarios, with a dose of 10 mg/kg every 6 hours.Cochrane Database Syst Rev 2000;4:CD000249.12/11/201373Prof.Veerendrakumar, VIMS, Bellary.

superiority of tranexamic acid to luteal-phase progestins and NSAID BMJ 1996;313:57982

No statistically significant increase in VTE


Hormonal..

cyclic luteal-phase progestin therapy is significantly less effective in treating menorrhagia than NSAIDS, tranexamic acid, or danazol

In contrast, long-cycle, high-dose oral progestins have been shown to reduce menstrual losses for women with heavy menstrual bleeding.

There are no published trials investigating the impact of DMPA on abnormal uterine bleeding


Woman has never learned to live healthy & happy without progesterone coverage of estrogen primed state

Its not simply a Pregnancy Hormone. But in true sense, A Mother Hormone.


LNG-IUSMaximal Benefits Outweigh Minimal Risks.

A reduction in menstrual blood loss of 86% at 3 months and 97% at 12 months was demonstrated in a single-arm study on the use of the LNG-IUS in women with menorrhagia,

20-80% become amenorrhic by 12 months.12/11/201377Prof.Veerendrakumar, VIMS, Bellary.

Hurskainen et al. randomized women with menorrhagia to receive either a hysterectomy or insertion of the LNG-IUS. The two groups had similar health-related quality of life scores at 5 years. JAMA 2004;291:145663.

women awaiting hysterectomy,

Over two thirds of the women who had the LNG-IUS inserted cancelled their surgery versus just 14.3% in the control group. BMJ 199812/11/201378Prof.Veerendrakumar, VIMS, Bellary.

Danazol and gonadotropin-releasing hormone agonists will effectively reduce menstrual bleeding, and may be used for scenarios in which other medical or surgical treatments have failed or are contraindicated. (I-C).


SERMs The Designer EstrogensSERMs are designed to act in a specific ways at each of the receptor sites

J Clin Oncol 2000 18:3172-3186.

J Clin Oncol 2000 18:3172-3186.

EstrogensAntiestrogensSERMs

TomoxifineDroloxifineToremifineRaloxifineOrmeloxifine


Ideal SERM for DUBNo uterine stimulation Prevents bone lossHas no risk for breast cancerHas a positive effect on lipids & cardiovascular systemMaintains cognitive function of the brain


Ormelloxifene


Weekly twice for 12 weeksweekly once for 12 weeks

74 of 85 subjects (87%) showed a reduction in endometrial thickness

Only 8.2% of women needed hysterectomy

J Obstet Gynecol Ind vol. 54, No 1 2004


Amenorrhea with the therapy 18 patients (42.9%)

ovarian cyst (7.1%), cervical erosion and discharge (7.1%), gastric dyspepsia (4.8%), vague abdominal pain (4.8%) and headache (4.8%) J. Obstet. Gynaecol. Res. 2009

Ormeloxifene is more effective as compared to MPA in reducing the blood loss in the treatment of DUB.


Surgical managementindications--failure to respond to medical therapy,-inability to utilize medical therapies (i.e. side effects, contraindications),-significant anemia,-impact on quality of life, and-concomitant uterine pathology (large uterine fibroids, endometrial hyperplasia).12/11/201385Prof.Veerendrakumar, VIMS, Bellary.

2nd generation techniques recommendedSeveral non-hysteroscopic ablation techniques are currently available.

Balloon, microwave, and radiofrequency ablation devices have a large reported clinical experience.

avoids the use of operating room resources and general anaesthetic.

SOGC guidelines 2013


SOGC GUIDELINES 2013


HYSTERECTOMYTHE most definitive treatment.Consider the least invasive method.12/11/201388Prof.Veerendrakumar, VIMS, Bellary.

From Research to Practice

Long Way to Go..

Technology made large populations possible and large populations today make technology indispensible


12/11/201390Prof.Veerendrakumar, VIMS, Bellary. THANK YOU

Perimenopausal bleeding

Health & Medicine

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