Mood, depression, and reproductive hormones in the menopausal transition

https://doi.org/10.1016/j.amjmed.2005.09.033Get rights and content

This article focuses on a review of evidence related to the following 3 questions: (1) Does depression appear during the menopausal transition? (2) What factors influence the risk for depression during the menopausal transition? (3) Do age-related alterations in ovarian hormone secretion contribute to the development of depression in some middle-aged women? A brief background is provided on the importance of depressive disorders. Methodologic issues that have compromised previous studies investigating the possible relation between the menopausal transition and depression are discussed. Evidence is presented that suggests a relation between the perimenopause (the interval between the early menopausal transition and 1 year after the last menses), but not the postmenopause, and the onset of depressive illness. Finally, studies are reviewed that suggest an association between alterations in ovarian function and depression, including several randomized placebo-controlled trials examining the antidepressant efficacy of estradiol in depressed perimenopausal and postmenopausal women.

Section snippets

What is the evidence of an association between the menopausal transition and depression?

The majority of women do not develop depression during the menopausal transition; therefore, the perimenopause is not uniformly associated with changes in a woman’s mood.11, 12, 14, 15, 16, 17 In fact, epidemiologic studies examining sex- and age-related differences in the 6-month to 1-year prevalence of major depression reported no increased prevalence of major depression in women at midlife (age range, approximately 45 to 55 years).1 Nonetheless, although the postmenopause is not associated

What factors influence the risk for depression during the menopausal transition?

As described in the previous section, several epidemiologic studies have surveyed the presence of depressive symptoms in women at midlife and identified rates of depressive symptoms ranging from 8% to 40%.18, 28 However, the samples in these studies consisted of women at midlife who were in different phases of reproductive aging, and depressive symptoms often were assessed independently of the presence of clinically meaningful depressive syndromes. These findings, therefore, are not directly

What is the evidence that age-related alterations in ovarian hormone secretion contribute to the development of depression in some middle-aged women?

There have been no differences in plasma levels of reproductive or adrenal (i.e., dehydroepiandrosterone) hormones identified consistently in women with perimenopausal depression compared with control subjects. Thus, depression during the perimenopause is not distinguished by abnormally low plasma levels of estrogens or androgens.30 However, 3 double-blind placebo-controlled trials using similar methodologies and identical preparations of estrogen (i.e., 17β-estradiol), have examined the

Summary

Recent evidence from prospective epidemiologic studies suggests that for some women the endocrine events (e.g., alterations in gonadotropin secretion, decreased estradiol secretion) during the perimenopause are associated with the onset of depression. Additionally, although perimenopausal depression is not characterized by abnormalities of basal ovarian hormone secretion, 2 randomized controlled trials reported therapeutic benefits of estradiol in perimenopausal depressed individuals. The

Acknowledgment

The author acknowledges the thoughtful contributions to the manuscript provided by Dr. David R. Rubinow.

References (36)

  • J.E. Zweifel et al.

    A meta-analysis of the effect of hormone replacement therapy upon depressed mood

    Psychoneuroendocrinology

    (1997)
  • J.C. Montgomery et al.

    Effect of oestrogen and testosterone implants on psychological disorders in the climacteric

    Lancet

    (1987)
  • R.C. Kessler et al.

    Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United Statesresults from the National Comorbidity Survey

    Arch Gen Psychiatry

    (1994)
  • A.D. Lopez et al.

    The global burden of disease, 1990–2020

    Nature Med

    (1998)
  • L.L. Judd et al.

    Subsyndromal symptomatic depressiona new mood disorder?

    J Clin Psychiatry

    (1994)
  • J. Spijker et al.

    Duration of major depressive episodes in the general populationresults from the Netherlands Mental Health Survey and Incidence Study (NEMESIS)

    Br J Psychiatry

    (2002)
  • S. Sherman

    Defining the menopausal transition

    Am J Med

    (2005)
  • M.B. First et al.
    (1996)
  • Cited by (80)

    • The role of estradiol fluctuation in the pathophysiology of perimenopausal depression: A hypothesis paper

      2021, Psychoneuroendocrinology
      Citation Excerpt :

      We furthermore provide a brief overview of the neuroendocrine mechanisms potentially mediating the effect of E2 changes on mood, and finish with a discussion of proposed clinical implications and future research. E2 withdrawal has long been hypothesised to be involved in the development of perimenopausal depressive symptoms (Schmidt, 2005). The fact that depression risk declines considerably in the late postmenopausal phase suggests that low but stable E2 levels are not problematic – rather, research evidence suggests that the decline from reproductive levels of E2 to postmenopausal levels are most likely to trigger depressive mood.

    • Reducing depression during the menopausal transition with health coaching: Results from the healthy menopausal transition randomised controlled trial

      2016, Maturitas
      Citation Excerpt :

      The menopausal transition (MT) is often described as a period of increased vulnerability to depressive symptoms [1,2], with most longitudinal studies demonstrating an increase in the prevalence of depression during this period [3,4]. Changes in gonadotrophins and/or sex steroids [5,6], history of past depression, vasomotor symptoms, weight gain, physical inactivity, poor social support, changing psychosocial roles, chronic diseases, and perceived loss of control have all been implicated as risk factors [7–11]. Despite growing recognition that women in the MT may be more susceptible to depression, no systematic attempts have been made to prevent this happening.

    • Puberty and perimenopause: Reproductive transitions and their implications for women's health

      2015, Social Science and Medicine
      Citation Excerpt :

      Women may also be more susceptible to high anxiety during perimenopause: at least one study has found that odds of high anxiety peak during late perimenopause—although not among women with high anxiety upon entering the menopausal transition (Bromberger et al., 2013). Higher prevalence of mood disorders and symptoms during puberty and perimenopause is usually tied to fluctuations in sex hormones (Angold et al., 1999; Freeman et al., 2006, 2004; Goodyer et al., 2001; Goodyer et al., 2000; Halbreich and Kahn, 2001; Nolen-Hoeksema, 2001; Schmidt, 2005; Steiner et al., 2003). Most theories propose one of two types of models to explain the developmental rise of mood disorders during reproductive transitions: an indirect model whereby hormones affect some general physiological system such as psychological arousal, neurotransmitters, or reactivity to stressors that increases risk for mood disorders; or an interaction model in which social context or environments, in addition to hormones, contribute to risk (Hyde et al., 2008).

    • Women's Health, Neurology of

      2014, Encyclopedia of the Neurological Sciences
    View all citing articles on Scopus

    The opinions offered at the National Institutes of Health (NIH) State-of-the-Science Conference on Management of Menopause-Related Symptoms and published herein are not necessarily those of the National Institute on Aging (NIA) and the Office of Medical Applications of Research (OMAR) or any of the cosponsoring institutes, offices, or centers of the NIH. Although the NIA and OMAR organized this meeting, this article is not intended as a statement of Federal guidelines or policy.

    Publication of the online supplement was made possible by funding from the NIA and the National Center for Complementary and Alternative Medicine of the NIH, US Department of Health & Human Services.

    View full text