Depression in the Menopause and Perimenopause

Depression in the Menopause

and Perimenopause

David A. Forstein, DO, FACOOG, (Dist)

Associate Professor of Obstetrics and Gynecology

University of South Carolina School of Medicine Greenville

Residency Program Director and Vice Chairman of Clinical Affairs, Department of Obstetrics and Gynecology

Learning Objectives

• Understand the updated terminology of the perimenopause and menopause

• Describe contributing factors to perimenopausal depression

• Know hormonal and non-hormonal

LITERATURE REVIEW

• COCHRANE REVIEWS

– MENOPAUSE – 18

– PERIMENOPAUSE - 2 – DEPRESSION – 497

– MENOPUASE AND DEPRESSION – 3

– PERIMENOPAUSE AND DEPRESSION -1 – No useful information

LITERATURE REVIEW

• RCTs

– MENOPAUSE – 5096 – PERIMENOPAUSE - 74 – DEPRESSION – 15667

– MENOPAUSE AND DEPRESSION – 199

• In 2001, the Stages of Reproductive Aging Workshop (STRAW) established a

nomenclature for reproductive aging

• In 2011, STRAW+10 updated and modified the model

Stages of Reproductive

Aging Workshop

STRAW+10

• The time around the FMP, also called “the menopause transition”

• Begins with variation in the menstrual cycle length of >7 days associated with a rise in

follicle-stimulating hormone (FSH) and ends 1 year after the FMP

• Often the most symptomatic phase for women

Harlow SD Menopause 2012;19:387-95

• The years after the FMP or after the

cessation of ovarian function in case of earlier hysterectomy

• Currently 1/3 to 1/2 of the lifespan of most North American women

Demographics

Quality of Life

The Seven Dwarfs

of Menopause

• Noteworthy signal of a new phase in a woman’s life

• The end of the female reproductive phase

• Opportunity for reassessment of health status and health goals

Menopause is a health

milestone

• In a survey of 12,275 perimenopausal women about their attitudes toward menopause, the mean score for all ethnic groups studied was positive.

• In a Gallup survey of 752 women concerning life

changes since menopause, a strong majority thought the following were either unchanged or improved: role at work, family life, partner/sexual relationship,

friendships, self-fulfillment, and physical health.

Sommer B Psychosom Med 1999;61:868-75; Utian WH Menopause 1999;6:122-8

What do women think

about menopause?

Contributing Factors to Depression in the Perimenopause and

Menopause • Intrinsic – Weight gain – Decline in fertility – Hot flashes – Vaginal dryness – Sleep disturbances – Cognitive changes – Disease risk with

aging • Extrinsic – Career issues – Teenagers – Empty nest – Sandwich generation – Husbands • Disabled • Divorced • Dead

• Feelings of upset, loss of control, irritability,

fatigue, and blue moods (dysphoria) at midlife may be caused by fluctuating hormone levels that perturb neural systems transiently

• Women with a history of premenstrual syndrome, significant stress, sexual

dysfunction, physical inactivity, or hot flashes are vulnerable to depressive symptoms

Dreher JC Proc Natl Acad Sci USA 2007;104:2465-70; Schmidt PJ Arch Womens Ment Health 2004;7:19-26

• The most predictive factor for depression at midlife and beyond is prior history of clinical depression

• Relaxation and stress reduction techniques, counseling, psychotherapy, and/or

antidepressants are options to consider in symptom management

Freeman EW Arch Gen Psychiatry 2006;63:375-82

Mood disorders

(continued)

• Importance of sexuality remains relatively constant

• Sexual desire declines

• Pain with intercourse increases

• Frequency of sexual activity remains relatively constant despite reports of dryness/discomfort

Avis NE Menopause 2009;16:442-52

Effect of perimenopause

on parameters

Effect of medroxyprogesterone on depressive symptoms in depressed and non-depressed perimenopausal and postmenopausal women following discontinuation of transdermal

estradiol therapy

• Objective –

– Does MPA use lead to depressive symptoms in two groups of peri- and postmenopausal women randomly assigned to estrogen treatment; one currently

experiencing depression and another without depression

• Study Design

– Open label MPA 10mg/day for 14 days, for

endometrial protection after treat of transdermal

estradiol 0.1mg/day for 8-12 weeks in 40-60 year old women in two separate RCTs for treatment in

depressed and non-depressed women – Beck Depression Inventory (BDI)

MPA and Depression

• Results

– 24 non-depressed and 14 depressed women – No change in BDI score

Rognines-Velo MP, Menopause. 2012; 19:471-75

• Conclusions

– Short term MPA use is not likely to cause

A Pilot Randomized, Single Blind,

Placebo-Controlled Trial of Traditional Acupuncture for Vasomotor

Symptoms and Mechanistic Pathways of Menopause

• 12 week study

• 3 treatments/week

– Traditional acupuncture (TA) – Sham acupuncture (SA)

– Waiting control (WC)

• Vasomotor Symptoms Score • Beck Depression Index (BDI)

• Speilberg State-Trait Anxiety Instrument

Acupuncture

Increased Estradiol and Improved Sleep, but not Hot Flashes, Predict Enhanced Mood During the

Menopausal Transition

• Estrogen is thought to enhance mood through CNS effects

• Women with depression, hot flashes, and sleep disturbance

• Randomized to transdermal E2 0.05mg/day, Zolpidem 10mg/day, or placebo for 8 weeks • Measures

– Montgomery-Asburg Depression Rating Scale (MADRS)

Estradiol, Hot Flashes and Depression

• No significant difference between groups in depression improvement

• Increased E2 levels and sleep improved mood statistically (p<0.001)

• Reduced hot flashes did not improve mood

Eszopiclone improves insomnia and depressive and anxious symptoms in perimenopausal and postmenopausal women with hot flashes: a

randomized, double-blinded, placebo-controlled crossover trial

Eszopiclone Study

Eszopiclone in Patients With

Insomnia During Perimenopause and Early Postmenopause

Obstet Gynecol 2006;108:1402–10

Eszopiclone in Patients With

Insomnia During Perimenopause and Early Postmenopause

Obstet Gynecol 2006;108:1402–10

.

• Methods

– 4 week study, RCT, placebo controlled

– Montgomery-Asberg Depression Rating Scale (MADRS)

• Results

– Pts on Eszopiclone showed improvements in all sleep measures and MADRS scores (p<0.05)

• Conclusions

– Improving sleep measures also improves mood scores

Escitalopram versus ethinyl estradiol and norethindrone acetate for

symptomatic peri- and postmenopausal women: impact on depression,

vasomotor symptoms, sleep, and quality of life

40

women

Escit

(n=16)

EPT

(n=16)

Escitalopram versus ethinyl estradiol and norethindrone acetate

Montgomery-Asberg Depression Rating Scale <10)

Escit 75% (12/16) p=0.01 EPT 25% (4/16)

Remission of Menopause Related Symptoms

Escit 56% (9/16) p=0.03 EPT 31.2% (5/16)

• Sleep, hot flashes, and QOL improved with both treatments

Escitalopram versus ethinyl estradiol and norethindrone acetate

• Conclusions

– ESCIT is more efficacious than EPT for the treatment of depression and has a positive

impact on other menopause-related symptoms

Kronos Early Estrogen Prevention Study (KEEPS) and the KEEPS

Cognitive and Affective Sub Study (KEEPS Cog)

• 9 sites

• RCT, double-blind, placebo-controlled

• Primary endpoint – Does HT started early in menopause prevent atherosclerosis

• Women 42-58

• 6-36 months postmenopausal • FSH>35

• CEE 0.45 vs Climara 50ug

Prometrium 200mg x 12 days • June 2005

KEEPS Cog

• Test at baseline, 18, 36, and 48 months • Profile of Mood States

• Beck Depression Inventory

KEEPS Cog

• Results

• HT improves symptoms of depression and anxiety in recently postmenopausal women without adverse affects on cognition

KEEPS Cog

• Results

• POMS – oCEE improved depression (p=0.03) and anxiety (p=0.02)

“

Be careful about reading

health books. You may die of

a misprint”

Conclusions

• Depression in the menopause and

perimenopause has many contributing factors • Prior diagnoses of depression or mood

disorders confers greater risk

• Treatment options like sleep aids and antidepressants are effective against depression

• Oral CEE is more effective than transdermal E2 for depression