Depression in the Menopause and Perimenopause

Transcription

1 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 Greenville Health System

2 The Corvette

3 Learning Objectives Understand the updated terminology of the perimenopause and menopause Describe contributing factors to perimenopausal depression Know hormonal and non-hormonal treatments for menopausal depression

4 LITERATURE REVIEW COCHRANE REVIEWS MENOPAUSE 18 PERIMENOPAUSE - 2 DEPRESSION 497 MENOPUASE AND DEPRESSION 3 PERIMENOPAUSE AND DEPRESSION -1 No useful information

5 LITERATURE REVIEW RCTs MENOPAUSE 5096 PERIMENOPAUSE - 74 DEPRESSION MENOPAUSE AND DEPRESSION 199 PERIMENOPAUSE AND DEPRESSION -15

6 Stages of Reproductive Aging Workshop In 2001, the Stages of Reproductive Aging Workshop (STRAW) established a nomenclature for reproductive aging In 2011, STRAW+10 updated and modified the model Soules MR Menopause 2001;8:402-7; Harlow SD Menopause 2012;19:387-95

7 STRAW+10 Harlow SD Menopause 2012;19:387-95

8 Perimenopause 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

9 Postmenopause 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

10 Demographics In million postmenopausal women in the US 40 million were >51 years old By 2020 >50 million women will be >51 years old

11 Quality of Life 80% of menopausal women experience report no decrease in QOL 75% denied loss in attractiveness 62% reported positive attitudes toward menopause Somer B, et al. Psychosom Med 1999;61:

12 The Seven Dwarfs of Menopause Itchy Bitchy Sweaty Sleepy Bloated Forgetful All-Dried-Up

13 Menopause is a health milestone 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

14 What do women think about menopause? 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

15 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

16 Mood disorders 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: ; Schmidt PJ Arch Womens Ment Health 2004;7:19-26

17 Mood disorders (continued) 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

18 Effect of perimenopause on parameters of sexual functioning 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

19 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 year old women in two separate RCTs for treatment in depressed and non-depressed women Beck Depression Inventory (BDI) Rognines-Velo MP, Menopause. 2012; 19:471-75

20 MPA and Depression Results 24 non-depressed and 14 depressed women No change in BDI score Conclusions Short term MPA use is not likely to cause mood disturbances Rognines-Velo MP, Menopause. 2012; 19:471-75

21 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 (STAI) Menopause 2012;19:54-61

22 Acupuncture Menopause 2012;19:54-61

23 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) J Clin Endocrinol Metab 2011;96: E

24 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 J Clin Endocrinol Metab 2011;96: E

25 Eszopiclone improves insomnia and depressive and anxious symptoms in perimenopausal and postmenopausal women with hot flashes: a randomized, double-blinded, placebo-controlled crossover trial Am J Obstet Gynecol 2010;202:171.e1-11.

26 Eszopiclone Study Am J Obstet Gynecol 2010;202:171.e1-11.

27 Eszopiclone in Patients With Insomnia During Perimenopause and Early Postmenopause Obstet Gynecol 2006;108:

28 Eszopiclone in Patients With Insomnia During Perimenopause and Early Postmenopause 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 Obstet Gynecol 2006;108:

29 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) Menopause 2006;13:780-86

30 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) EPT 31.2% (5/16) p=0.03 Sleep, hot flashes, and QOL improved with both treatments Menopause 2006;13:780-86

31 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 Menopause 2006;13:780-86

32 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 months postmenopausal FSH>35 CEE 0.45 vs Climara 50ug Prometrium 200mg x 12 days June women

33 KEEPS Cog Test at baseline, 18, 36, and 48 months Profile of Mood States Beck Depression Inventory Brief Patient Health Questionnaire

34 KEEPS Cog Results HT improves symptoms of depression and anxiety in recently postmenopausal women without adverse affects on cognition 0CEE>transdermal E2

35 KEEPS Cog Results POMS ocee improved depression (p=0.03) and anxiety (p=0.02)

36 Be careful about reading health books. You may die of a misprint -Mark Twain

37 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

38 Questions