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Healthy Transitions: Maintaining Mental Health

though the Menopausal Transition

Katherine L. Wisner, M.D., M.S.

Norman and Helen Asher Professor of Psychiatry and Obstetrics and Gynecology

Director, Asher Center for Research and Treatment of Depressive Disorders

Member, Institute for Women’s Health Research

Feinberg School of Medicine

Northwestern University, Chicago IL

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The Longitudinal Laboratory of Women’s Lives

MenarcheMenarchePremenstruumPremenstruum

PregnancyPregnancyPostpartumPostpartumMenopauseMenopause

Menstrual Cycle ChangesMenstrual Cycle Changes

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STRAW +10 Stages(Stages of Reproductive Aging Workshop)

Menopause 2012. 19(4): 387-95.

Challenges for Midlife Women

Average age 51 yearsAverage age 51 years Systemic Problems related to estrogen decreaseSystemic Problems related to estrogen decrease

• Hot flushesHot flushes• Insomnia, Irritability, Depression, Mood labilityInsomnia, Irritability, Depression, Mood lability• Memory changesMemory changes• Bone lossBone loss• Cardiovascular healthCardiovascular health

Focal Problems Focal Problems • Vaginal drynessVaginal dryness• Vaginal atrophyVaginal atrophy• Pain with intercoursePain with intercourse• Urinary problemsUrinary problems

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Challenges for Midlife Women

During the menopausal transition, depression affects between 12-23% of women aged 40-59 years

>43 million women (14% of US population) who have among the highest rates of depression of any demographic

The majority of women do not develop depression (“empty nest syndrome, involutional melancholia”) !!

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MenopauseMenopause Risk for depression especially women with previous Risk for depression especially women with previous

episodesepisodesEstrogen withdrawal theoryEstrogen withdrawal theory Estrogen enhances serotonergic and noradrenergic Estrogen enhances serotonergic and noradrenergic

transmission transmission Domino theoryDomino theory Somatic symptoms, especially sleep disturbance, Somatic symptoms, especially sleep disturbance,

anxiety, sexual dysfunction, create risk for anxiety, sexual dysfunction, create risk for depression as a down-line effectdepression as a down-line effect

Life stage perspectiveLife stage perspective Changing family or professional roles, interpersonal Changing family or professional roles, interpersonal

losses, aging and physical illnesslosses, aging and physical illness

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EpidemiologyMajor Depression-

Major Public Health Impact

• Depression is common. • Globally, >350 million people of all ages suffer. • Depression is the leading cause of disability

worldwide, and a major contributor to the global burden of disease.

• Twice as many women are affected as men.• Lifetime, Female (F)=21%; Male (M)=12%• Annual, F=13%, M=8%• There are effective treatments for depression!

www.who.int/mediacentre/factsheets/fs369/en/index.html

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Gender Differences in the Prevalence of Major Depression

Women have twice the rate relative to menWomen have twice the rate relative to men

Kessler et al (1993) Journal of Affective Disorders

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Clinical Presentation: Major Depression

For two weeks, most of the day nearly For two weeks, most of the day nearly every day, 5 of these (one must be mood or every day, 5 of these (one must be mood or interest):interest):

Depressed moodDepressed mood Diminished interest/pleasureDiminished interest/pleasure Weight loss/ gain unrelated to dietingWeight loss/ gain unrelated to dieting Insomnia/ hypersomniaInsomnia/ hypersomnia Psychomotor agitation/ retardationPsychomotor agitation/ retardation Fatigue or loss of energyFatigue or loss of energy Feelings of worthlessness/guiltFeelings of worthlessness/guilt Diminished ability to concentrateDiminished ability to concentrate Recurrent thoughts of deathRecurrent thoughts of deathNIMH--MDD in Women brochure for patients: NIMH--MDD in Women brochure for patients: www.nimh.nih.gov/health/publications/women-and-www.nimh.nih.gov/health/publications/women-and-depression-discovering-hope/index.shtmldepression-discovering-hope/index.shtml

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Pathophysiology:Pathophysiology: Individual and Social FactorsIndividual and Social Factors

Personality traits (passive, unassertive; ruminative) Personality traits (passive, unassertive; ruminative) associated with female gender and depression. associated with female gender and depression.

Close interpersonal relationships are relatively Close interpersonal relationships are relatively more important to women than men; disruptions in more important to women than men; disruptions in relationships are particularly stressful.relationships are particularly stressful.

Women more likely ruminate about interpersonal Women more likely ruminate about interpersonal difficulties and conflicts difficulties and conflicts

Less resource access: Full-time working women Less resource access: Full-time working women earn $0.77 per $1 a man earns: less money for earn $0.77 per $1 a man earns: less money for needs of their families, more women living in needs of their families, more women living in poverty, and far less savings for retirement.poverty, and far less savings for retirement.

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Pathophysiology:Pathophysiology: Life Stress and TraumaLife Stress and Trauma

Women experience more stressors more frequently Women experience more stressors more frequently than men. than men. • Childhood sexual abuse (6%-33%)Childhood sexual abuse (6%-33%)• Adult sexual assault (estimate 15%)Adult sexual assault (estimate 15%)• Male partner violence (WHO, 15%-71% across Male partner violence (WHO, 15%-71% across

10 countries)10 countries) Women are more likely to react to stressors with Women are more likely to react to stressors with

depression.depression. Frequent stressors and stress reactivity perpetuate Frequent stressors and stress reactivity perpetuate

and kindle womenand kindle women’’s vulnerability to depression over s vulnerability to depression over time.time.

(Nolen-Hoeksema, S. -Wye River, Oct. 2000)(Nolen-Hoeksema, S. -Wye River, Oct. 2000)

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Pathophysiology Biological DifferencesBiological Differences

Depressive illnesses are brain disorders Depressive illnesses are brain disorders Neural circuits for control of mood, thought, Neural circuits for control of mood, thought,

sleep, appetite, and behavior are dysregulated.sleep, appetite, and behavior are dysregulated. Depression results from influence of multiple Depression results from influence of multiple

genes acting together with environmental genes acting together with environmental factors.factors.

Depressive symptoms are associated with Depressive symptoms are associated with ovarian hormone fluctuation, but there is no ovarian hormone fluctuation, but there is no relationship between serum levels and relationship between serum levels and depressed mooddepressed mood

Affected woman have enhanced neurobiological Affected woman have enhanced neurobiological sensitivity to hormonal fluctuation.sensitivity to hormonal fluctuation.

Most women do not experience significant Most women do not experience significant mood problems during reproductive transitions.mood problems during reproductive transitions.

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Evidence Based Interventions: Evidence Based Interventions: PsychotherapyPsychotherapy

Several types of short-term (8-16 sessions, Several types of short-term (8-16 sessions, focused psychotherapy)focused psychotherapy)

Patient choice, access, depression severity Patient choice, access, depression severity Interpersonal Psychotherapy targets Interpersonal Psychotherapy targets

interpersonal distress and effect on mood interpersonal distress and effect on mood www.apa.org/divisions/div12/rev_est/ipt_depr.htmlwww.apa.org/divisions/div12/rev_est/ipt_depr.html

Cognitive Behavior Therapy – correct distorted Cognitive Behavior Therapy – correct distorted and dysfunctional automatic thoughtsand dysfunctional automatic thoughtswww.beckinstitute.org/what-is-cognitive-behavioral-www.beckinstitute.org/what-is-cognitive-behavioral-therapytherapy

Dialectical Behavior Therapy--combines Dialectical Behavior Therapy--combines standard CBT techniques with skill building - standard CBT techniques with skill building - distress tolerance, acceptance, mindfulnessdistress tolerance, acceptance, mindfulnesshttp://behavioraltech.org/index.cfmhttp://behavioraltech.org/index.cfm

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All Antidepressants have Similar All Antidepressants have Similar EfficacyEfficacy Serotonergic (SSRI-sertraline, Serotonergic (SSRI-sertraline, fluoxetine; SNRI, venlafaxine)fluoxetine; SNRI, venlafaxine)• Comorbid Obsessive-compulsive disorderComorbid Obsessive-compulsive disorder• Hot flashesHot flashes• Side effects=Sexual dysfunction, weight gain, Side effects=Sexual dysfunction, weight gain,

nausea/ diarrhea, sleep disturbance, apathynausea/ diarrhea, sleep disturbance, apathyNorepinephrine (Tricyclics-Norepinephrine (Tricyclics-

nortriptyline, SNRI)nortriptyline, SNRI)• Serum level is meaningfulSerum level is meaningful• Side effects=Tremor, tachycardia, dry mouth, Side effects=Tremor, tachycardia, dry mouth,

insomnia, weight gaininsomnia, weight gain

Dopamine/Norepinephrine (bupropion)Dopamine/Norepinephrine (bupropion)• Smoking cessation Smoking cessation • Side effects=Agitation, psychosis, weight Side effects=Agitation, psychosis, weight

neutral/ appetite suppressionneutral/ appetite suppression

Personalize Antidepressant Personalize Antidepressant Choice Choice

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Perimenopausal Depression Treatment

Antidepressants and Psychotherapy first line Antidepressants and Psychotherapy first line Transdermal estradiol (E2), small RCTs positiveTransdermal estradiol (E2), small RCTs positive

•3-12 wk RCTs of E3-12 wk RCTs of E2 2 50-100 ug/d) vs Placebo50-100 ug/d) vs Placebo•68-80% response of E68-80% response of E22 vs 20% to Placebo vs 20% to Placebo

JJoffe et al, N=72offe et al, N=72•8 wk RCT E2 (50 ug/day), zolpidem, Placebo8 wk RCT E2 (50 ug/day), zolpidem, Placebo•Similar improvement across 3 groupsSimilar improvement across 3 groups

Morrison et al, N=72Morrison et al, N=72•E2 (100 mcg/day) E2 (100 mcg/day) notnot efficacious compared efficacious compared to PL after 8 weeks in to PL after 8 weeks in older older (mean=62 years) (mean=62 years) post-menopausal women post-menopausal women •For E2 treatment: STRAW -1 to +1a and 1bFor E2 treatment: STRAW -1 to +1a and 1b

Post-meno. women respond more favorably to Post-meno. women respond more favorably to tricyclics (nortriptyline) than to SSRItricyclics (nortriptyline) than to SSRI

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Estradiol Treatment Complex relationship between gonadal hormones and Complex relationship between gonadal hormones and

depression depression Not a hormone deficiency: Levels of FSH and E2 do not Not a hormone deficiency: Levels of FSH and E2 do not

distinguish women with/ without depressiondistinguish women with/ without depression Response to E2 is not predicted by baseline or post-Response to E2 is not predicted by baseline or post-

treatment E2 levelstreatment E2 levels E2 has antidepressant properties E2 has antidepressant properties The mood enhancing effects of E2 occurs independent The mood enhancing effects of E2 occurs independent

of the presence of hot flashesof the presence of hot flashes SSRI/SNRI reduce vasomotor symptoms, but not as SSRI/SNRI reduce vasomotor symptoms, but not as

effective as E2effective as E2

Environmental Approaches

Aerobic Exercise (> 30 minutes of moderate intensity physical exercise, 3 to 5 days per week) Dunn et al, Am J Prev Med 2005;28:1-8, 2005

Nutritional status; Vitamin D . EMAS position statement: Vitamin D and postmenopausal healthPerez-Lopez et al, Maturitas 71:83-88, 2012

Essential Fatty Acids for Cardiac Health/ Depression/ Immune Function

1-2 grams of EFA/day as in AHA recommendations; Reviews: Freeman et al. J Clin Psych 67, 2006; Parker et al, Am J Psych 163:969-978, 2006

Bright Morning Light Therapy Bright Morning Light

Therapy, 10,000 lux commercial UV blocked box

Center for Environmental Therapeutics, tools at www.cet.org APA review and meta-analysis- Am J Psych 162:656-662, 2005

Data support efficacy in non-seasonal depression: a non-pharmacologic somatic RX for depression

2020

WARNING!WARNING!

Insufficient Medical ResearchInsufficient Medical ResearchCan be HazardousCan be Hazardous to your Health to your Health

C. Everett Koop, M.D.C. Everett Koop, M.D.