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A prospective study of the association between endogenous hormones and depressive symptoms in postmenopausal women

Ryan, Joanne MSc1,2,3; Burger, Henry G. MD4; Szoeke, Cassandra MBBS, PhD1; Lehert, Philippe PhD5; Ancelin, Marie-Laure PhD2,3; Henderson, Victor W. MD, MS6; Dennerstein, Lorraine MBBS, PhD1

doi: 10.1097/gme.0b013e31818d635f

Objective: Across a woman's lifetime, variations in hormone levels are known to influence mood and well-being. Whether absolute or changes in hormone levels over time are associated with depression among postmenopausal women remains unclear.

Methods: The Melbourne Women's Midlife Health Project is a longitudinal population-based study of women who were followed through the menopausal transition. This analysis is based on data collected from 138 postmenopausal women in years 11 and 13 of the study, who were assessed for the presence of depressive symptoms using the Center for Epidemiological Studies Depression Scale. Logistic regression models were developed to determine whether absolute or changes in hormone levels were associated with depression.

Results: No significant associations were found between depressive symptoms and the absolute levels of sex hormone-binding globulin, testosterone, free androgen index, estradiol, free estradiol, or follicle-stimulating hormone (FSH). On the other hand, women with a decline in total serum estradiol over the 2-year period had a more than threefold increased risk of depressive symptoms (odds ratio, 3.5; 95% CI, 1.2-9.9). A large increase in FSH levels over this period was also associated with depressive symptoms (odds ratio, 2.6; 95% CI, 1.0-6.7). These associations remained even after adjustment for initial depression score, as well as a range of potential confounding factors.

Conclusions: Changes in estradiol and, to a lesser extent, in FSH levels are associated with an increased risk of depressive symptoms in postmenopausal women. These results further support a role for fluctuating rather than absolute hormone levels in depression in later life.

In this population-based study of postmenopausal women, a 2-year decline in estradiol levels and, to a lesser extent, a large increase in FSH levels were associated with an increased risk of depressive symptoms. By contrast, there was no significant association between absolute levels of estradiol, FSH, estrone, testosterone or SHBG, and depressive symptoms.

From 1The University of Melbourne, Parkville, Victoria, Australia; 2Inserm U888, Montpellier, F-34093 France; 3University of Montpellier, Montpellier, F-34000 France; 4Prince Henry's Institute of Medical Research, Clayton, Victoria, Australia; 5University of Mons, Belgium; and 6Department of Health Research & Policy and of Neurology & Neurological Sciences, Stanford University, Stanford, CA.

Received July 21, 2008; revised and accepted September 10, 2008.

Funding/support: This study was supported by grants from the Victorian Health Promotion Foundation, the National Health and Medical Research Council of Australia, the Alzheimer's Association (IIRG-01-2684), and the University of Melbourne. Prince Henry's Institute of Medical Research received grants from Organon Pty Ltd for the hormone assays. Joanne Ryan has a PhD scholarship from the University of Melbourne, and Cassandra Szoeke is the recipient of a fellowship from the Royal Australian College of Physicians.

Financial disclosure: Professor Dennerstein reports from research support Organon, Wyeth, and Proctor & Gamble and from expert panel and consulting fees Pfizer, Wyeth, Boehringer Ingelheim, and Bayer Schering.

Address correspondence to: Joanne Ryan, MSc, Department of Psychiatry, The University of Melbourne, Level 1 North, Royal Melbourne Hospital, Grattan Street, Parkville, Victoria 3050, Australia. E-mail:

©2009The North American Menopause Society