Publications

OBJECTIVE: To compare the relationship between vasomotor symptoms (hot flushes and night sweats) and depression in perimenopausal women with that in postmenopausal and older premenopausal women.

DESIGN: Questionnaire data assessing current depressive symptoms (Center for Epidemiologic Studies Depression Scale), hot flushes, night sweats, menopausal status, depression history, hormonal therapy use, and demographic characteristics were collected from women aged 40 to 60 years seeking primary care. Multivariable logistic regression models were used to examine the relationship between vasomotor symptoms and depression.

RESULTS: Depression (defined by a Center for Epidemiologic Studies Depression Scale score >/= 25) was observed in 14.9% of 141 perimenopausal women, 13.9% of 151 postmenopausal women, and 7.6% of 184 older premenopausal women. Recent vasomotor symptoms were reported by 53.9% of perimenopausal women, 43.7% of postmenopausal women, and 20.7% of older premenopausal women. Perimenopausal women with vasomotor symptoms were 4.39 times more likely to be depressed than those without vasomotor symptoms (95% CI, 1.40-13.83), an association that did not change after controlling for depression history. In contrast with perimenopausal women, postmenopausal and older premenopausal women with vasomotor symptoms did not have a significantly greater risk for depression than women of the same menopausal status without vasomotor symptoms (adjusted odds ratios, 1.28 and 1.77; 95% CI, 0.47-3.46 and 0.53-5.89, respectively).

CONCLUSIONS: Hot flushes and night sweats are associated with depression in perimenopausal women. Further investigation is warranted to elucidate the mechanism by which hot flushes may be associated with depression in perimenopausal women and not in postmenopausal or older premenopausal women.

Treatment of major depression in menopausal women is controversial. Estrogen replacement therapy (ERT) treats mild depression but may not treat more severe depression in this population. Antidepressants are recommended as treatment for major depression in menopausal women, but the specific efficacy of antidepressants has not been examined in menopause-associated depression. Twenty-two perimenopausal and postmenopausal women aged 40-61 taking stable doses of ERT who met Structured Clinical Interview for DSM-IV (SCID-IV) criteria for major depression were accessioned into an open-label clinical trial of mirtazapine. Subjects were treated with 30-45 mg/day mirtazapine for 8 weeks and were assessed every 2 weeks with the Hamilton Depression Rating Scale-17 (HDRS-17), Beck Depression Inventory (BDI), and Clinical Global Impression (CGI) Scale. Remission of depression was defined as an HDRS-17 score < or =7 at the week 8 study visit. Sixteen (73%) of the enrolled subjects completed the 8-week study. The median HDRS-17 score declined from 20.5 (range 12-37) at baseline to 2 (range 0-9) at week 8 (Wilcoxon signed-rank test, p < 0.001). Remission of depression was achieved by 14 of 16 (87.5%) study completers. Subjects responded well to mirtazapine regardless of whether their depression preceded ERT use or developed after ERT was initiated. Therapeutic response also appeared independent of menopausal status (perimenopausal vs. postmenopausal), ERT preparation, and concomitant use of medroxyprogesterone. Mirtazapine is an effective treatment for major depression in perimenopausal and postmenopausal women whose depression precedes ERT use and does not respond to ERT or whose depression develops after ERT is initiated.

BACKGROUND: Results of previous studies suggest that estrogen improves somatic and mild depressive symptoms experienced by perimenopausal women. This study investigated the efficacy of 17beta-estradiol for the treatment of clinically significant depressive disorders in endocrinologically confirmed perimenopausal women.

METHODS: Perimenopausal women (aged 40-55 years, with irregular menstrual periods and serum concentrations of follicle-stimulating hormone >25 IU/L), meeting criteria for major depressive disorder, dysthymic disorder, or minor depressive disorder, according to DSM-IV, were randomized to receive transdermal patches of 17beta-estradiol (100 microgram) or placebo in a 12-week, double-blind, placebo-controlled study. A 4-week washout period followed the 12-week treatment phase. Outcome measures were the Montgomery-Asberg Depression Rating Scale and Blatt-Kupperman Menopausal Index scores.

RESULTS: Fifty women were enrolled in the study; 26 met DSM-IV criteria for major depressive disorder, 11 for dysthymic disorder, and 13 for minor depressive disorder. Remission of depression was observed in 17 (68%) women treated with 17beta-estradiol compared with 5 (20%) in the placebo group (P =.001). Subjects responded similarly to estradiol treatment, regardless of DSM-IV diagnosis. Patients treated with estradiol sustained antidepressant benefit of treatment after the 4-week washout period, although somatic complaints increased in frequency and intensity. Treatment was well tolerated and adverse events were rare in both groups.

CONCLUSION: Transdermal estradiol replacement is an effective treatment of depression for perimenopausal women.

A growing body of literature describes the effects of estrogen and other gonadal steroids on the central nervous system. The ability of estrogen to modulate serotonergic function, in particular, raises the possibility that sex steroids may play a role in the mechanisms associated with depression and its treatment. This review will focus on those aspects of the estrogen-serotonin interaction that relate to possible increased vulnerability to affective disorders and on hormonal treatments that may be clinically applicable to women. After a discussion of the potential relationship between estrogen and mood disorders across the female life cycle, a model is proposed in which differential sensitivity to mood disorders explains the differential response by some women to periods of normal hormonal changes. Possible serotonin receptor-mediated and intracellular mechanisms by which estrogen may exert its effects on mood are also reviewed. These are compared to putative mechanisms of standard antidepressant effect. Lastly, treatment studies in which estrogen has been used as 1) monotherapy for depression, 2) an augmentation strategy, or 3) a prophylactic intervention against recurrence of depression are reviewed.