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The Harvard Study of Moods and Cycles

Bernard L. Harlow, PhD; Lauren A. Wise, MSc; Michael W. Otto, PhD; Claudio N. Soares, MD, PhD; Lee S. Cohen, MD

Arch Gen Psychiatry. 2003;60:29-36.

Background  Few studies have determined the impact of a lifetime history of major depression on an early transition to menopause.

Methods  Reproductive and psychiatric interviews and early follicular-phase blood specimens were obtained at study enrollment and every 6 months during 36 months of follow-up from 332 women with and 644 women without a history of major depression, 36 to 45 years of age. We used menstrual cycle markers to determine inception of perimenopause, defined as time from study enrollment to a follow-up interview with: (1) 7-day or more change in menstrual cycle length; (2) a change in menstrual flow amount or duration; or (3) amenorrhea lasting at least 3 months.

Results  Women with a history of depression had 1.2 times the rate of perimenopause of women with no such history (95% confidence interval, 0.9-1.6). Compared with nondepressed women, depressed women with more pronounced depressive symptoms at study enrollment (Hamilton Rating Scale for Depression scores >8) had twice the risk of an earlier perimenopausal transition. Among the women with greater depressive symptoms (Hamilton scores >8), those who also reported use of antidepressants had nearly 3 times the risk of an earlier perimenopausal transition (hazard ratio, 2.7; 95% confidence interval, 1.5-4.8) of nondepressed women. Women with a lifetime history of depression also had higher follicle-stimulating hormone and luteinizing hormone levels and lower estradiol levels at study enrollment and during the follow-up period after adjustment for covariates.

Conclusion  A lifetime history of major depression may be associated with an early decline in ovarian function.

From the Obstetrics and Gynecology Epidemiology Center, Brigham and Women's Hospital and Harvard Medical School (Dr Harlow and Ms Wise), and the Perinatal Psychiatry Clinical Research Program, Massachusetts General Hospital and Harvard Medical School (Drs Otto, Soares, and Cohen), Boston, Mass.

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