Contraception and HRT for Women in Contemporary Clinical...

Ed ti l C C t ti dEducational Course: Contraception and HRT for Women in Contemporary

Clinical PracticeClinical Practice

HOW HORMONE THERAPY MAY HELP SEXUAL FUNCTION AT MENOPAUSE

Dr. Santiago PalaciosgInstituto Palacios, Salud y Medicina de la Mujer

Antonio Acuña, 9 - 28009 Madrid – Spain - Phone +34 91 578 05 17E-mail: [email protected] @ p

www.institutopalacios.com

www.institutopalacios.com

Diapositivas / Slides

Natural vs Surgical Menopause

Natural Menopause Surgical MenopausePhysiological processNatural transition Gradual decline of sex hormone levels Gradual, variable presence of symptoms

Medical intervention (potentially distressing)Sudden onsetSteep decline of sex hormone levelsStronger, more severe symptoms

Menopause↓Hormone levels↓Hormone levels

End of fertile phase

Symptoms/ImpactHot flushes

Sleep disturbanceMood changesgMemory loss

Loss of energyUrogenital problemsSexual problemsp

Adapted from Nappi RE et al. Gynecol Endocrinol 2006; 22:318-323Source: FSDeducation.eu

Role of Estradiol & Testosterone in the Onset of Sexual Symptoms at MenopauseOnset of Sexual Symptoms at Menopause

Estradiol DeficiencyH t fl h / t

Testosterone DeficiencyDiminished sense ofHot flushes/sweats

Sleep disturbanceMood changes

Diminished sense ofwell-beingDecreased energyI d d iVaginal dryness Increased depressionReduced sexual desire, receptivity and arousal

Impairment of Sexual Function

Source: FSDeducation.eu

“Domino Effect” of Climacteric C l i t S l S tComplaints on Sexual Symptoms

NegativeEmotional Feelings

SEXUALity

(depression, anxiety,panic, loss of interest…)

SEXUALDYSFUNCTION

Inte

nsi

Poor Physical Health(loss of fitness, fatigue,weight gain headache )I weight gain, headache…)

Genito-Urinary Problems(recurrent vaginal infections(recurrent vaginal infections,involuntary loss of urine…)

RE Nappi et al, 2002

Nappi RE, et al. (2002) Gynecol Obstet Invest; 53: 181-7

Body PhysiologyBody Physiology

PartnerHormones

BrainBrain

SEXUAL FUNCTIONSEXUAL FUNCTION

Mean Plasma Hormone Levels:Pre and Post Menopausal

ld

Pre- and Post-Menopausal

Below assay Below assay 40 ± 3Oestradiol (pg/ml)

Surgical Menopause (Oophorectomy)Natural MenopauseReproductive

Age

100 ± 20200 ± 20

detection limit

((400 ± 30Testosterone

detection limit40 ± 3Oestradiol (pg/ml)

1260 ±

100 ± 20

1970 ±

200 ± 20

((4200 210DHEA ( / l)

(75%)

(50%)400 ± 30(pg/ml)

Androgens are present at higher circulating levels than oestradiol

1260 ±360

1970 ±430

(70%)

(53%)4200 ± 210DHEA (pg/ml)

Androgens are present at higher circulating levels than oestradiolAndrogen levels fall more dramatically after surgical menopausePost menopause, androgen levels decline by 50% compared with

Lobo, RA (2001) Obstet Gynecol Surv 56: 361-76

pre-menopausal levels

Menopause-Associated Clinical Profile

Hormonal InstabilityInstability

SleepHotDepression

Sleepdisturbance

Hotflashes

Windows of Vulnerability y

•Heightened prevalence of psychiatric conditions during periods of intense hormone

i bilit fl t ti ( PMDD PPD)variability, fluctuation (e.g., PMDD, PPD)

•Symptoms adverse outcomes resulting from •Symptoms, adverse outcomes resulting from the disruption of hormone milieu

•Windows of sexual dysfunction

Cohen LS et al Arch Gen Psychiatry 2006;63:385-390Cohen LS, et al. Arch Gen Psychiatry. 2006;63:385-390.Soares CN. Expert Rev Neurother. 2007;7:1285-1293. Rocca W, et al. Neurology. 2007;69:1074-1083.Almeida OP, et al. Arch Gen Psychiatry. 2008;65:283-289.

Windows of Opportunity pp y

•A stable hormone milieu or a hormone •A stable hormone milieu or a hormone intervention may exert a prophylacticeffect effect

•Hormone intervention/modulation may •Hormone intervention/modulation may exert a therapeutic effect

Soares CN, et al. Arch Gen Psychiatry. 2001;58:529-534. Rocca WA, et al. Neurology. 2007;69:1074-1083.Joffe H, et al. J Clin Psychiatry. 2007;68:943-950.

Hot Flashes and Night SweatsHot Flashes and Night Sweats

• Hot flashes and night sweats may be associated with hormonal changes1,2

Night sweatsHot flashes - transient Night sweats– Drenching perspiration– Usually associated

Hot flashes transient episodes

– Warming sensation Usually associated with sleep disruptionto intense heat

– Reddening of the kiskin

– Perspiration

1. Kronenberg F. Ann N Y Acad Sci. 1990;592:52-86.2. North American Menopause Society. Menopause. 2004;11:11-33.

Hot Flashes: EpidemiologyHot Flashes: Epidemiology

Prevalence of Hot Flashes by Age (N=1400)100

80

90

100sh

es (

%)

1968-1969

1974 1975

Assessment year

Onset: as early as 38 years of agePrevalence peak: age 52 to 54 years

60

70

ng h

ot f

las 1974-1975

1980-1981

Prevalence peak: age 52 to 54 yearsMay persist up to 72 years of age

40

50

peri

enci

n

10

20

30

Wom

en e

xp

3

0

10

38 44 46 50 52 54 56 58 60 62 66 72

W

Data in this graph represent information collected at three intervals: 1968-1969, 1974-1975, 1980-1981.Rödström K, et al. Menopause. 2002;9:156-161.

Age (years)

For How Long Can Hot Flushes Continue? g

Number of years women report having hot flushes as estimated by a survey of 501 untreated women who experienced hot flushes40

45

50

untreated women who experienced hot flushes

25

30

35

Numberof

10

15

20of Subjects

0 2 4 6 8 10 12 14 16 18 20 22 24 28 30 36 410

5

10

Years after menopause

Kronenberg F. 1990

Hypothesis of Thermoregulatory Dysfunction: Core Body Temperature ThresholdsCore Body Temperature Thresholds

SymptomaticNormal Symptomatic

Sweating

Normal

Sweating

Upper threshold(Upper set

Sweating

h l

Sweating

(Upper set point)

Lower

Thermoneutral Zone

(homeostatic range)

CBT

Lower threshold(Lower set point) ShiveringShivering

Body temperature

Body temperature

Freedman RR. Am J Med. 2005;118:124S-130S

Factors that Influence the Thermoneutral Zone: The Role of 5-HT, NE and Estrogens , gModulation

Sweating Threshold

+

AsymptomaticEstrogen

Decreased Body

ratu

re +

ThermoneutralZone

Hot Flushes

Clonidine

SSRI 5-HT*

Decreased Sympathetic NS† Activity

Tryptophan Depletion

yohimbine

Core

BTe

mpe

r

Shivering

−

Threshold

* 5 HT = serontonin (5 hydroxytryptopan) 5-HT = serontonin (5-hydroxytryptopan)† NS=nervous system

HT AND VASOMOTOR SYMPTOMSHT AND VASOMOTOR SYMPTOMS

•No other medical treatment nor alternative one best offer significant relief of VMSReducing frequency and intensity is as high as 90% •Reducing frequency and intensity is as high as 90%

and sustained•The main effect was observed in the course of a The main effect was observed in the course of a month with fixed dose and route of administration

RESPONSE TO DIFFERENT DOSES OF CEE ALONE OR WITH MPA

A BPlacebo

0.3 mg/dX Placebo

0.3/1.5 mg/dX

12

10

8num

ber

12

10

8num

ber

XX X X X X X

0.45 mg/d

0.625 mg/d

0.45/2.5 mg/d

0.625/2.5 mg/d

XX X X X X

6

4

uste

d m

ean

6

4

uste

d m

ean

X X XX X X X

X X X X XX X X X

1 2 3 4

2

0

Adj

u

Week5 6 7 8 9 10 11 12 1 2 3 4

2

0

Adj

u

Week5 6 7 8 9 10 11 12

CEE Alone CEE + MPA

Utian, et al. Fertil Steril. 2001.75;1065.

Ultra-low doseNo. of moderate and severe hot flushes per week

PlaceboUltra-low dose

Vaginal Atrophy*significantly (p=0.001) g y (p )different from placebo

Maturation Vaginal pH

Panay N et al. Climacteric 2007;10(2):120–131

Effects of E+T vs T alone over 2 years on l f tisexual function

1098765

SexualityScale

E IMPLANTSE+T IMPLANTS

Libido

ActivityScale Activity

Satisfaction

Pleasure

Fantasy

Orgasm

Relevancy

Davis et al Maturitas 1995

Transdermal Testosterone Plus OestrogenPhase III testosterone patch studies in surgically p g ymenopausal women

• Two Separate Phase III Clinical Trials:

S i l 1 (INTIMATE SM 1) 562 – Surgical menopause 1 (INTIMATE SM 1), n=562 women– Surgical menopause 2 (INTIMATE SM 2), n=532 women

• Objective:– Assess efficacy / safety of transdermal testosterone in surgically menopausal

women with Hypoactive Sexual Desire Disorder

• Design:– 24-week randomised, double-blind, placebo-controlled, multinational trial– Placebo or transdermal testosterone patch 300 μg/day– All patients on oral or transdermal oestrogenp g– Inclusion / Exclusion criteria similar

• Female testosterone patch: Alcohol free translucent matrix patch– Alcohol-free, translucent, matrix patch

– Twice-a-week application to abdomen– Contains 8.4 mg testosterone– Delivers 300 μg/day testosterone

Simon JA, et al. (2005) J Clin Endocrinol Metab 90: 5226–5233 Buster JE et al. (2005) Obstet Gynecol 105: 944–952


APHRODITE (Transdermal Testosterone Patch Only) I d PFSF D i t 24 W kIncreased PFSF Domains at 24 Weeks

25

30Placebo

(SEM

)

* *Transdermal Testosterone Patch (300μg/day)

20

25

m B

asel

ine

*

** *

10

15

hang

e fr

om * *

0

5

Mea

n C

h

0Arousal PleasureOrgasm Reduced

Concerns Responsive-

nessSelf-imageDesire

**p<0.05, vs. placebo

Hormonal TreatmentTib lTibolone

• Tibolone is a synthetic steroidTibolone is a synthetic steroid

• It has oestrogenic, androgenic and progestogenic properties

Tibolone is indicated for the relief of climacteric symptoms in post menopausal • Tibolone is indicated for the relief of climacteric symptoms in post-menopausal women

• Data suggest a positive effect on sexual symptoms comparable to hormonal therapy via

– interaction of the the 4-isomer of tibolone with AR. d SHBG t ti d th b i – decrease SHBG concentrations and thereby increase the availability of T.

• Good overall tolerability with low incidence of vaginal bleeding and breast tenderness

• Current available data on breast and endometrial cancer risk are inconclusive• Current available data on breast and endometrial cancer risk are inconclusive

• Potential increase in risk of strokeSource: FSDeducation.eu

TIBOLONE improves sexual function in postmenopausal womenPalacios et al 1995 Palacios et al 1995

1.6Tibolone (n=14)

1.2

Tibolone (n=14)Placebo (n=14)

0.8

0.4

0

-0.4

Tibolone significantly different for all values at p <0.01 at 12 m

Causes of Sexual Arousal Disorder (SAD)( )

Major Biological Causes1 Psychological CausesMajor Biological Causes1

• Sex hormone deficiency• Diabetes/Vascular factors

Psychological Causes• Relationship issues• Intrapersonal issues

• Smoking• Pelvic floor disorders

• Intrapersonal issues

• Lower urinary tract symptoms (LUTS)

• Pelvic surgery

Sociocultural Causes• Poverty/Low income

• Pelvic surgery• Neurological diseases• Drugs: Anti-hormones,

• Working conditions• Sexual norms

chemotherapy

1For clinical purposes the biological focus is on factors affecting genital arousalSource: FSDeducation.eu

Latent classes analysisof FSD by risk factorsof FSD by risk factors

Predictors Sexual pain Arousal disorders

Adjusted OR (95% CI)

Predictors pdisorders

LLower

Urinary Tract Symptoms

7.61 4.02Symptoms (4.06-14.26) (2.75-5.89)

Laumann, Paik & Rosen, JAMA, 1999

Estradiol deficiency

Vulvo-vaginal atrophy

D i / it l l Dyspareunia / genital arousal

Negative effecton sexual function

CONSEQUENCES AND MANAGEMENT OF UROGENITAL ATROPHYUROGENITAL ATROPHY

UROGENITAL ATROPHY

1 UG changes in menopause1 UG changes in menopause

2 Prevalence of vaginal atrophy

3 Management options

4 Hormone therapy.Vaginal route

5 Potencial barriers to management UGA5 Potencial barriers to management UGA

Postmenopausal changes in the vaginal mucosa

Premenopausal Postmenopausal

VaginaF ld

Erectile tissue

Loss of folds

Folds or rugae

Muscular coat

I li i L f i Inner mucous liningcontains large

amount glycogen

Loss of inner mucous lining and glandular function

Vaginal Changes in Menopause

B f • Before menopause– Vaginal epithelium is thick and nonkeratinized– Glycogen is abundantGlycogen is abundant– Normal acidic pH is 3.5 to 4.5

Impact of menopause on the urogenital Urogenital

system• Impact of menopause on the urogenital system – Estrogen declines

system

Estrogen declines– Vaginal epithelium loses rugae– Tissues grow thin and pale– Vaginal secretions decrease– Glycogen diminishes

V i l H i– Vaginal pH increases

Pandit and Ouslander. Am J Med Sci 1997; 314:228-231.

Compared to premenopausal women, postmenopausal ith t g d fi i hwomen with estrogen deficiency have

FEWER:– Facultative lactobaccilli

Gardenerella aginalis– Gardenerella vaginalis– Coryneforms– YeastsYeasts– Prevotella bivia– Staphlococci– Mycoplasma hominis – Ureaplasma urealyticum

BUT MORE:Coliforms – Coliforms

– Streptococi viridans

Atrophic vaginitis under the microscopep g p

Normal:Squamous cellsCells with enough cytoplasm an low nucleus/cytoplasm ratio

Atrophic vaginitis:Presence of parabasal cellsSquamous cells with enlarged nucleuslow nucleus/cytoplasm ratio

Pyknosis presentnucleusInflammation exudat“Blue Blobs” – characteristic, round basophilic structuresround basophilic structures

Bachmann GA, Nevadunsky NS; http://www.aafp.org/afp/20000515/3090.html; Accessed May 2004 & October 2006

Vaginal Atrophy

S t P t l P l • Symptoms– Vaginal dryness– Decreased lubrication

Postmenopausal woman treated with estrogen

Postmenopausal woman without estrogen

Decreased lubrication– Discomfort, burning,

soreness

• Predisposition to:

– Urinary tract infectionsParabasal

cellsSuperficial

cells

– Vaginal infections

• Advanced signsRugae

– Contraction of vagina– Loss of distensibility Vaginal

epitheliump

Pandit, et al. Am J Med Sci. 1997;314:228-31.


UROGENITAL ATROPHY

1 UGA changes in menopause




5 Potencial barriers to management UGA

Increase in Vaginal Dryness with Menopause

50

with Menopause

40

30

erce

nt

10

20Pe

0

10

Pre Early Late Post Post PostPre-menopause(n = 172)

EarlyPeri-

menopause(n = 148)

LatePeri-

menopause(n = 106)

Post-menopause

1 year(n = 72)

Post-menopause

2 years(n = 54)

Post-menopause

3 years(n = 31)

Dennerstein L, et al. Obstet Gynecol. 2000;96:351-8. (Slide provided by the Council on Hormone Education, 2002)(Slide provided by the Council on Hormone Education, 2002)

( ) ( ) ( ) ( ) ( )

Dryness increased significantly in late perimenopause and postmenopause (P < .001).

©JL Alexander, www.afwh.org

RELEVANCE OF SEXUAL ISSUES AT MENOPAUSE

66%No periods for 1+ years

37%

43%

52%

I it bilitSleeplessness

Hot flushes

36%37%37%

Reduced sex driveMood swings or mood changes

Irritability

25%

28%Depression

Headaches or migraines

14%

21%21%

Very occasional periodsVaginal pain, dryness or discomfort

Involuntary urine loss

14%Very occasional periods

Q2A Are you currently experiencing or have you experienced any of the following in the past year?Base: Total Sample (n=1805) of European (from Italy Switzerland UK Germany France The Base: Total Sample (n=1805) of European (from Italy, Switzerland, UK, Germany, France, The Netherlands) menopausal women (age: 50-60 yrs) interviewed by phone

Nappi & Nijland, 2008

SEXUAL SYMPTOMS &SURGICAL MENOPAUSEVAGINAL DRYNESSQ Aft i l did

SEXUAL DESIREQ Aft i l did Q: After surgical menopause did you

noticed the appearance/worsening of…Q: After surgical menopause did younoticed a reduction of…

0 9%0 5%22.4%

0.9%20.2%

0.5%

55.5%46.8%

29.9%23.8%

Yes NoSample: 568 women withsurgical menopause

Most of the time No Answersurgical menopause

Nappi et al, submitted


UROGENITAL ATROPHY






MANAGEMENT OPTIONS

a) Lifestyle modifications

a) Non-hormonal treatment (lubricants, moisturizers)

a) Hormonal therapy, systemic or local a) Hormonal therapy, systemic or local

a) Others: herbal, soy, vitamins

LIFE STYLE MODIFICATIONS

1 .Cessation of smokinggKalogeraki. In Vivo. 1996

2 Sexual activity 2. Sexual activity. Both regular coital activity and masturbation provide protection

“USE IT OR LOSE IT”

Leiblum et al. JAMA. 1983

3. Cranberry - lingonberry juice concentrate reduces risk of UTIin postmenopausal women.

Kontiokari. BMJ. 2001

NON HORMONAL THERAPY

LUBRICANTS Temporary measures to relieve vaginal dryness during intercourse,

Combination of protectants and thickening agents in water soluble p g gbase.Short duration of action, needs frequent application and reapplication before sexreapplication before sex.

- Astroglide

- K-Y jelly

- Lubrin

- H-R jelly

- Surgilube Surgilube

- Touch Wilhite et al. Pharmacology. 2001

MOISTURIZERS

Bioadhesive polycarbophil-based polymer which adheres to mucin p y p p yand epithelial cells on vaginal wall

Carry up to 60x its weight in water and holds water in place y p g pagainst vaginal epithelium until cells sloughs off, about 24 hours.

2-3 applications per week.pp p

No need for reapplication prior to sex

Symptomatic relief, acidic PH

Some effect on vaginal elasticitySome effect on vaginal elasticity

Replens

Moist Again d d h M t it 1996Moist Again Bygdeman and Swahn. Maturitas. 1996


UROGENITAL ATROPHY






Meta analysis of placebo controlled trials revealed Meta analysis of placebo controlled trials revealed

estrogen to be more effective than placebo for all

variables measured

Cardozo et al.Obstet Gynecol. 1998

Th i l t f d i i t ti l t d ith b ttThe vaginal route of administration correlated with betterreports of symptomatic relief, greater improvement in cytologic findings


Low dose vaginal estradiol was the most efficacious


Major effect on patient report occurs between

1 and 3 months after the start of treatment and is maintained thereafter


Vaginal application formsg pp

Creams

Premarin®

i l

Vaginal Ring

Estring®

t i

Vagitories

Ortho Gynest®

i l t i l

Vaginal tablets

Vagifem®

fi t d l vaginal cream (PVC) conju-gated equine estrogens (CEE)

contains estradiol,releases estradiol in a consistent

vaginal estriol suppositories

first and only vaginal oestrogen tablet

Estrace®

estradiol cream in an applicator-free tube

a consistent manner over 90 days

free tube

Vagifem® 10µg provides a very low dose f t di lof estradiol

• 1.14 mg exposicion annual al estrogenoDose and administration

Initial Dose:1 tablet inserted into the vaginadaily for 2 weeks. = 14 tabletsMaintenance:

bl d ll k1 tablet inserted vaginally twice per weekfor 50 weeks = 100 tabletas

Total per year:Total per year:114 tablets x 10µg = 1140µg

1140µg of estradiol1140µg of estradioladministered to the patient in 1 year = 1.14 mg

Degree of vaginal healthg g

2,0

2,5lt

h

1,5

inal

Hea

l

0 5

1,0

core

Vag

i

p<0.001

p<0.001 p<0.001 p<0.001 p<0.001

0,0

0,5

Mea

n S

Baseline 2 4 8 12 (LOCF)52 (LOCF)Weeks

Placebo 10µg E2

Simon JA et al. Obstetrics & Gynecology 2008; 12(5): 1053–60

Other Treatments - SERMs

• SERMs elicit different effects in differential tissues– Agonist (bone)– Antagonist (breast)

• Previous SERMs have different actions:– Tamoxifen and raloxifene both act as antagonist in the breast and

agonist in the boneg– Only tamoxifen acts as agonist in the uterus– Neither tamoxifen nor raloxifene have an effect on the vagina

• New SERM – Lasofoxifene

– Agonist behavior in bone, the vagina, and the cardiovascular system g , g , y

– Antagonist behavior in breast and uterine tissue

• New SERM ospemifenep

Dutertre, Smith. Pharmacol and Experimental Therapeutics. 2000;295:431-7.


UROGENITAL ATROPHY






Initiation of dialogue about vaginal dryness

WWomen

Selection:respondents having discussed “vaginal dryness” with physician?

6680

(%

)

respondents having discussed vaginal dryness with physician?

40

56

40

60

espo

nden

ts

27

20

Perc

ent

of r

e

0The doctor Respondent herself

Non HRT-patients (n = 74) HRT-patients (n = 189)

P

HRT Market Understanding, TNS EMNID 2002

p ( ) p ( )

Potential Barriers to Discussing S l H lth ith P ti tSexual Health with your Patients

Patient barriers Doctor barriersPatient barriers• Emotional factors

(shame, anxiety, embarrassment)Age (life stage)

• Embarrassment1

• Feeling overwhelmed by more urgent healthcare issues• Age (life stage)

• Perception that sexual functioning is not an important medical problem

urgent healthcare issues• Lack of specific training in sexual

medicine2

F li th ti ll h l l• Lack of awareness about treatment possibilities

• Physician characteristics

• Feeling therapeutically helpless • Lack of awareness of associated

comorbid conditions(gender, age, speciality)

Contextual barriersf f• Lack of confidentiality

• Lack of privacy• Poor reimbursement3

1. Korenman S.G (1998) Am J Med. 105: 135-144; 2. Broekman CPM, et al.(1994) Int J Impot Res. 6: 67-72;3. Baum N, et al.(1998) Patient Care Spring (suppl):17-21


Co-occurrence of Core M “B i ” SMenopause “Brain” Symptoms

SleepVasomotor Symptoms Symptoms

Depression

Odds Ratios (ORs) of Hormones From the Final Multivariable Model for Onset of Depressive Symptoms (CES-D Scale Score >= 16) for 116 Participants

At the time of high CES-D scores a At the time of high CES D scores, a woman was more likely to have an increased variability around her own levels of estradiol (P 03) FSH levels of estradiol (P = .03), FSH (P<.001), and LH (P = .005) than she did before the high CES-D scores

Freeman E W et al Arch Gen Psychiatry 2006;63:375 382

Copyright restrictions may apply.

Freeman, E. W. et al. Arch Gen Psychiatry 2006;63:375-382.

Risk of First Onset of Depressive Symptoms in Premenopausal and PerimenopausalWomen With No Lifetime History of Major DepressionWomen With No Lifetime History of Major Depression

Cohen, L. S. et al. Arch Gen Psychiatry 2006;63:385-390.

PREMENOPAUSAL WOMEN WITH NO LIFETIME HISTORY OF MAJOR DEPRESSION WHO ENTERED PREMENOPAUSAL WOMEN WITH NO LIFETIME HISTORY OF MAJOR DEPRESSION WHO ENTERED THE PERIMENOPAUSE WERE NEARLY TWICE AS LIKELY TO DEVELOP DEPRESSIVE SYMPTOMS AS WOMEN WITH NO HISTORY OF DEPRESSION WHO REMAINED PREMENOPAUSAL

EFFECTS OF E/TE ON FUNCTIONAL MRI

Estrogen Modulation of Key Regions/SystemsBrain regions involved in mood and menopausal symptomsBrain regions involved in mood and menopausal symptoms

= Areas directly influenced by estrogen

Estrogen has multiple effects on neurotransmitter systems and brain regions involved in mood and menopausal symptoms menopausal symptoms (VMS)

During times of estrogenDuring times of estrogenfluctuations/decline, loss of these effects might predispose some women to dysregulation of affected brain regions

Figure adapted from Charney DS. Am J Psychiatry. 2004;161:195-216.

brain regions

Effects of estrogens on serotonergic and noradrenergic neuronsnoradrenergic neurons

Deecher et al. Psychoneuroendocrinology 2008; 33:3-17

Am J Obstet Gynecol 2009

Estrogen Therapy for M R l t d D iMenopause-Related Depression

Treatment n Population Main FindingsTreatment n Population Main Findings

Transdermal E2(50 mcg/d), DB, PL, 6 weeks1

36 Perimenopausal women with depressive disorders

• POSITIVE: Partial/full response –80% with E2, 22% with placebo. No association with hot flashes


50 Perimenopausal women with depressive disorders

• POSITIVE: Remission – 68% with E2, 20% with placebo. Sustained antidepressant response despite , , p p precurrence of hot flashes

Oral E2 (0.3 mcg/d),

3

10 Perimenopausal women with major depression

• POSITIVE: Remission in 60% of patients treated with E2

open, 8 weeks3

Transdermal E2(100 mcg/d), open 4 weeks4

22 Mixed menopausal status with depressive disorders

• POSITIVE: Peri: 66% remission• NEGATIVE: Post: 18% remission

open, 4 weeks4


57 Postmenopausal women with depressive disorders

• NEGATIVE: Response to E2(40%) was similar to placebo (44%), , ( )

DB = double-blind; PL = placebo-controlled.

1. Schmidt PJ, et al. Am J Obstet Gynecol. 2000;183:414-420. 2. Soares CN, et al. Arch Gen Psychiatry.2001;58:529-534. 3. Rasgon NL, et al. Am J Psychiatry. 2001;158:1738. 4. Cohen LS, et al. Am J Psychiatry. 2003;160:1519-1522. 5. Morrison M, et al. Biol Psychiatry. 2004;55:406-412.

Conclusion HT

•Impact on the risk for depression, sleep disruption, VMS, cognitive decline

•Impact on brain functioning/structure

• Impact on depressive symptoms, response to tid tantidepressants

Impact on sexual function•Impact on sexual function

Contraception and HRT for Women in Contemporary Clinical...

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