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Entering menopause increases the risk of first episode depression
  1. Nancy Fugate Woods, PhD, RN, FAAN
  1. Dean and Professor, University of Washington School of Nursing,
    Seattle, WA, USA

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Q Does entering menopause increase the risk of depression in women without a history of depression?


Embedded ImageDesign:

Prospective cohort study.

Embedded ImageFollow up period:

Six years.

Embedded ImageSetting:

Seven communities in Boston, Massachusetts, USA; time period not stated.

Embedded ImagePeople:

643 pre-menopausal women aged 36–45 years old from the Harvard Study of Moods and Cycles who had never had major depression (DSM-IV) were enrolled. Final analyses only included 420 of these women, who completed the last follow up interview, did not become menopausal, did not have vasomotor symptoms without meeting criteria for peri-menopause, and were not taking oral contraceptives.

Embedded ImageRisk factors:

Menopausal status (pre-menopausal v peri-menopausal) determined by self report changes in menstrual cycle. Peri-menopause was defined as any of the following occurring in the period before the follow up interview: skipped periods, a change in menstrual flow amount (change of ⩾2 categories, for example light to moderately heavy or heavy) or duration (change of ⩾2 days), or a change in menstrual cycle length (⩾7 days compared with baseline). Telephone assessment was performed every six months for the first three years, and then by a postal questionnaire at six years.

Embedded ImageOutcomes:

Onset of depressive symptoms, assessed in the first three years with the Structured Clinical Interview for DSM-IV, Outpatient Version; subsequently with the Center for Epidemiological Studies Depression Scale (CES-D) for symptoms in the prior month, and for other times three questions asking whether they had experienced: (a) feeling depressed or down most of the time for two weeks; (b) loss of interest or pleasure in usually enjoyable things; or (c) being bothered by depressed mood greater than half the time. Depression was defined as a CES-D score ⩾16 or answering “yes” to one of the three questions.


Women who had entered peri-menopause were more likely to develop new onset depressive symptoms compared with women who remained pre-menopausal (results after controlling for age at study enrolment and past history of adverse life events: 106/326 (32.5%) peri-menopausal women v 19/95 (20.0%) pre-menopausal women; OR 1.8, 95% CI 1.0 to 3.2).


Entering peri-menopause increases the risk of developing new onset depression in women without a history of depression.


After decades of associating menopause and the empty nest with midlife depression, results from a series of studies suggested that menopause and depression were unrelated.1,10 However, a resurgence of interest in menopause has produced evidence to the contrary. Cohen et al report that pre-menopausal women with no lifetime history of major depression who entered the peri-menopause were almost twice as likely to develop significant depressive symptoms as women who remained pre-menopausal. Coupled with results of another recent study,11 these findings prompt us to revise our thinking about the menopausal transition and depression.

Although we are tempted to link depression to changing biology coinciding with the beginning of the menopausal transition, data about women’s experiences of depression during the late menopausal transition stage (when they are skipping periods) or to post-menopause are rare. What we may be observing in these contemporary studies is a period of vulnerability to endocrine change that is consistent with the stress-diathesis model of depression in which a changing hormonal milieu may lower the threshold for depression should negative life events occur.12 Cohen et al found that women with high life stress were at significantly greater risk of developing a first episode of depression as they transitioned to peri-menopause compared with those women without such high life stress. Recognising that the menopausal transition may be a period of vulnerability in a woman’s life is an important consideration when counselling women about managing their menopausal symptoms.



  • For correspondence: Lee S Cohen, MD, Perinatal and Reproductive Psychiatry Clinical Research Program, Massachusetts General Hospital, 15 Parkman Street, WACC815, Boston, MA 02114, USA; lcohen{at}

  • Source of funding: National Institute of Mental Health, Bethesda, MD.