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Longitudinal prospective cohort study.
Follow up period:
Philadelphia County, USA; timeframe not stated
436 initially premenopausal women (218 white, 218 African American; mean age at endpoint 44.6 years, range 38–52 years) with 22–35 day menstrual cycles, an intact uterus and at least one ovary. Exclusions: psychotropic or hormonal medication, pregnancy, breastfeeding, compromised ovarian function, or substance abuse.
Data were collected during six assessments, approximately every 8 months. Trained researchers collected blood samples for hormone assays (obtained between days 2 and 6 of consecutive menstrual cycles); administered a structured interview to assess general health status and behaviour, and the Center for Epidemiology Studies Depression Scale (CES-D). Major depressive disorder was assessed according to DSM-IV criteria. At each interview, menopausal status was determined.
Depressive symptoms (CES-D; a cut off score of ⩾16 defined high depressive symptoms); MDD; menopausal status determined with the Staging System for Reproductive Aging in Women (premenopausal: regular 22–35 day menstrual cycle; early menopause: change in cycle length by more than a week for two cycles; late menopause: absence of menstruation for 3–11 months; postmenopausal: absence of menstruation for more than 12 months); predictor variables (including hot flashes, sleep pattern, employment status, history of depression, PMS severity).
Data are presented for 76% of the original sample (332 women). 21% of women had a history of depression at baseline. At 4 years, 3% were postmenopausal, 3% in late menopause, 21% in early menopause, and 73% remained premenopausal. Depressive symptoms were more likely during early and late transition to menopause than pre or post menopause. History of depression, severe PMS, and poor sleep increased likelihood of depression in menopausal women (see http://www.ebmentalhealth.com/supplemental for table).
Depression significantly increases in women as they reach menopause but decreases once menopause is complete.
The study by Freeman and colleagues is important because it periodically obtained blood samples from a prospective cohort of premenopausal women not initially using hormones, who were followed over a significant number of years (4 years). Consistent with prior work, depressive symptoms, as measured by the CES-D, significantly increased during the perimenopausal stage and decreased after menopause. However, the question of whether hormonal shifts during perimenopause increased depressive symptoms, or that climacteric symptoms were interpreted as depressive symptoms remains unanswered. It is unclear whether clinicians should treat the depressive symptoms, treat the climacteric symptoms, a combination of the two, or wait until women pass through to menopausal stages.
Randomised placebo controlled trials have not consistently found that use of an oestrogen/progesterone combination improves mood.1,3 However, in the HERS trial, the benefit of hormone therapy (HT) was observed among women experiencing flushing,4 but no significant relation was observed for women not experiencing flushing. The frequent administration of progesterone with oestrogen confounds exploration of the antidepressant role of HT. In our own study of community women aged 45–54 years, increased climacteric symptoms (hot flashes, trouble sleeping, night sweats, memory problems, mood swings) explain the observed increased rates of depressive symptoms among women of this cohort (almost 30% reported high levels of depressive symptoms as measured by a shortened CES-D).5 Even after considering HT, climacteric symptoms remained significantly related to increased depressive symptoms.
Although there is suggestive evidence from observational studies and a limited number of randomised, controlled trials that oestrogen therapy improves mood and cognition, the clinical relevance of oestrogen administration is unproved. There are weak data that oestrogens might be considered for mild depressive symptoms attributed to hot flushes, sleep disturbances, or other climacteric symptoms. No hard data exist to indicate whether oestrogen could be used as adjunctive therapy for other depressive disorders during the menopausal transition or postmenopausal period. The use of antidepressants is the only proven treatment at this time.
Review history and Supplementary material
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- [View PDF] - Table Predictors of CES-D and MDD scores (multivariate analysis)
For correspondence: Ellen Freeman, Department of Obstetrics/Gynecology, University of Pennsylvania School of Medicine, 3701 Market Street, Suite 820, Philadelphia, PA, USA;
Sources of funding: funded by grants to the principal investigator (EF) and to the General Clinical Research Center, University of Pennsylvania Medical Center from the National Institutes of Health, Bethesda, MD, USA.
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