Menopause and Mood Disorders 

  • Author: Stacey B Gramann, DO, MPH; Chief Editor: Iqbal Ahmed, MBBS, FRCPsych (UK)   more...
 
Updated: Aug 18, 2011
 

Background

Menopause is the permanent cessation of menstruation resulting in the loss of ovarian follicle development. It is considered to occur when 12 menstrual cycles are missed.[1, 2]

Menopausal transition, or perimenopause, is a defined period of time beginning with the onset of irregular menstrual cycles until the last menstrual period, and is marked by fluctuations in reproductive hormones.[3] This period is characterized by menstrual irregularities; prolonged and heavy menstruation intermixed with episodes of amenorrhea, decreased fertility, vasomotor symptoms; and insomnia. Some of these symptoms may emerge 4 years before menses ceases, with a perimenopausal mean age of onset of 47.5 years.[4] During the menopausal transition, estrogen levels decline and levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) increase. Postmenopause is the phase following the last menstrual period.

Depression during menopause

In the United States, 1.3 million women reach menopause annually. Although most women transition to menopause without experiencing psychiatric problems, an estimated 20% have depression at some point during menopause.[5]

Studies of mood during menopause have generally revealed an increased risk of depression during perimenopause with a decrease in risk during postmenopausal years.

The Penn Ovarian Aging Study, a cohort study, showed depressive symptoms increased during the menopausal transition, and decreased after menopause. The strongest predictors of depressed mood was a prior history of depression, along with fluctuations in reproductive hormone levels associated with depressed mood.[6]

In a cross-sectional population survey from the Netherlands, 2103 women were asked to rate their symptoms of depression before menopause and 3.5 years later, during the menopausal transition. The women experienced most symptoms of depression during the menopausal transition. In the United States, a study of a community sample of women undergoing natural menopause also demonstrated an increase in depressive symptoms during perimenopause.[7]

Investigators from the Harvard Study of Moods and Cycles recruited premenopausal women aged 36-44 years with no history of major depression and followed up these women for 9 years to detect new onsets of major depression. Women who entered perimenopause were twice as likely as women who had not yet made the menopausal transition to have clinically significant depressive symptoms.[8]

Recent research has shown that reproductive hormones produced during menopause contribute to mood alterations, such as depression. Higher testosterone levels may directly lead to higher depressive symptoms during the menopausal transition. Menopausal status, however, remains an independent predictor of depressive symptoms.[9]

Problems with sleep during menopause

Insomnia occurs in 40-50% of women during the menopausal transition, and problems with sleep may or may not be connected to mood disorders.[10] Women with insomnia are more likely than others to report problems such as anxiety, stress, tension, and depressive symptoms.

Sleep disturbances during menopause have been associated with estrogen deficiency, as exogenous estrogen has been shown to improve both subjective and objective sleep, attributed to a decrease in hot flashes. A recent study proposed elevated LH levels during late menopause produce poor sleep quality through a thermoregulatory mechanism, resulting in high core body temperatures.[11] Whether the sleep problems are associated with age-related changes in sleep architecture, hormonal status, or other symptoms of menopause (eg, vasomotor symptoms) is unclear. However, in the Medical Research Council National Survey of Health, women who were transitioning into menopause were more likely to report severe sleep difficulty compared with women who were premenopausal.[12]

Rates of sleep apnea increase with age, rising from 6.5% in women aged 30-39 years to 16% in women aged 50-60 years. The pathophysiology is not known, but theories include a relationship to postmenopausal weight gain or to decreased progesterone levels because progesterone stimulates respiration.[13, 14] In addition to undergoing changes in estrogen and progesterone levels, postmenopausal women experience a decline in melatonin and growth hormone levels, both of which have effects on sleep.[15]

Schizophrenia during menopause

In most cases, schizophrenia first manifests in young adulthood, with the rate of new cases declining in both male and female individuals after early adulthood. A second peak in the incidence of schizophrenia is noted among women aged 45-50 years; this second peak is not observed in men.[16]

Some researchers have observed a worsening of the course of schizophrenia in women during the menopausal transition. These observations may suggest that estrogen plays a modulatory role in the pathophysiology of schizophrenia.[17]

Panic disorder during menopause

Panic disorder is common during perimenopause. New-onset panic disorder may occur during menopause, or preexisting panic disorder may worsen. Panic disorder may be most common in women with many physical symptoms of menopause.[18]

In a cross-sectional survey of 3,369 postmenopausal women aged 50-79 years, panic attacks were most prevalent among women in the menopausal transition. Panic attacks were associated with negative life events, functional impairment, and medical comorbidity.[19]

Obsessive-compulsive disorder during menopause

New-onset obsessive-compulsive disorder (OCD), a relapse of OCD, or a change in OCD symptoms may occur during menopause. Fluctuations in OCD have been correlated with the menstrual cycle and with pregnancy, suggesting that hormone levels may contribute to the disorder.[20]

Bipolar disorder during menopause

Exacerbation of mood symptoms during menopause has been noted in women with preexisting bipolar disorder. Research has suggested that women with bipolar disorder have higher rates of depressive episodes during the menopausal transition. The frequency of depressive episodes in this population appears to be higher than during premenopausal years.[21] Earlier studies suggested an increase in rapid cycling during the menopausal transition; however, this finding has not been reproduced.[22]

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Pathophysiology

Depression during perimenopause is likely due to fluctuating and declining estrogen levels in part. Steroid hormones, such as estrogen, act in the CNS by means of various mechanisms. For instance, they stimulate the synthesis of neurotransmitters, the expression of receptors, and influence membrane permeability.[23]

Estrogen increases the effects of serotonin and norepinephrine, which are thought to be the neurotransmitters most related to the physiologic cause of depression. Among other mechanisms, estrogen decreases monoamine oxidase (MAO) activity in the CNS, hindering the break down of serotonin and norepinephrine.[2] In addition, estrogen increases serotonin synthesis, upregulates 5-hydroxytryptamine (5-HT)-1 (5-HT1) receptors, and downregulates 5-HT2 receptors. Estrogen also increases norepinephrine activity in the brain, perhaps by decreasing reuptake and degradation due to inhibition of the enzymes MAO and catechol O-methyltransferase.[24]

Although the precise mechanisms are yet unknown, regulation of serotonin and norepinephrine may change as estrogen levels fluctuate and thus contribute to depression. Because estrogen facilitates the actions of serotonin and norepinephrine, a decline in estrogen concentrations may, in turn, decrease levels of these hormones.[2, 23, 24] Changes in estrogen levels, perhaps due to mechanisms involving these neurotransmitters, may be related to depressive symptoms in the menopausal transition of some women.

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Epidemiology

Frequency

United States

Each year, 1.3 million women reach menopause. An estimated 20% of these women experience depression.[5]

Mortality/Morbidity

Although morbidity and mortality secondary to perimenopausal depression has not been studied, depression is known to be a significant health problem in women. According to the World Health Organization's Global Burden of Disease Study, unipolar depression is the leading cause of disease-related disability in women.[25] In the Global Burden of Disease Study, unipolar major depression was second to only ischemic heart disease in terms of associated morbidity and mortality.[26]

The Study of Women's Health Across the Nation (SWAN) suggests women during and immediately after the menopausal transition are at higher risk for major depression, and the risk is smaller when they are premenopausal.[27]

Race

The racial distribution of perimenopausal depression is not known. However, in countries where older women are highly valued, women experience fewer symptoms overall during menopause.

Sex

Depression is approximately twice as common in women as in men (21% vs 12.7%). Moreover, depressive are more recurrent, longer, worse, and more impairing for women and for men.[28, 29] In addition, the prevalence of dysthymia and minor depression is increases among women. These differences have not been noted for mania. Sex-related differences emerge at the age of 11-15 years.[25]

Age

The mean age of onset for the menopausal transition is 47.5 years.[4]

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Contributor Information and Disclosures
Author

Stacey B Gramann, DO, MPH  Adult Psychiatry Resident, Psychiatry Residency Training Program, University of Massachusetts

Stacey B Gramann, DO, MPH is a member of the following medical societies: American Osteopathic Association, American Psychiatric Association, Massachusetts Medical Society, and Phi Beta Kappa

Disclosure: Nothing to disclose.

Coauthor(s)

Rebecca S Lundquist, MD  Consulting Staff, Department of Psychiatry, UMass Memorial Medical Center

Rebecca S Lundquist, MD is a member of the following medical societies: American Psychiatric Association

Disclosure: Pfizer Salary Employment; Biogen Salary Employment

Specialty Editor Board

Mohammed A Memon, MD  Chairman and Attending Geriatric Psychiatrist, Department of Psychiatry, Spartanburg Regional Medical Center

Mohammed A Memon, MD is a member of the following medical societies: American Association for Geriatric Psychiatry, American Medical Association, and American Psychiatric Association

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Harold H Harsch, MD  Program Director of Geropsychiatry, Department of Geriatrics/Gerontology, Associate Professor, Department of Psychiatry and Department of Medicine, Froedtert Hospital, Medical College of Wisconsin

Harold H Harsch, MD is a member of the following medical societies: American Psychiatric Association

Disclosure: lilly Honoraria Speaking and teaching; Forest Labs None None; Pfizer Grant/research funds Speaking and teaching; Northstar None None; Novartis Grant/research funds research; Pfizer Honoraria Speaking and teaching; Sunovion Speaking and teaching; Otsuke Grant/research funds reseach; GlaxoSmithKline Grant/research funds research; Merck Honoraria Speaking and teaching

Chief Editor

Iqbal Ahmed, MBBS, FRCPsych (UK)  Faculty, Department of Psychiatry, Tripler Army Medical Center; Clinical Professor of Psychiatry, Clinical Professor of Geriatric Medicine, University of Hawaii, John A Burns School of Medicine

Iqbal Ahmed, MBBS, FRCPsych (UK) is a member of the following medical societies: Academy of Psychosomatic Medicine, American Association for Geriatric Psychiatry, American Neuropsychiatric Association, American Psychiatric Association, American Society of Clinical Psychopharmacology, and Royal College of Psychiatrists

Disclosure: Nothing to disclose.

Acknowledgments

The authors and editors of eMedicine gratefully acknowledge the contributions of previous author Sarah Langenfeld, MD to the development and writing of this article.

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