In this issue of JAMA Psychiatry, Gordon et al1 report results from a 12-month randomized clinical trial of estrogen plus progestin hormone therapy (HT) vs placebo for the prevention of depressive symptoms in 172 euthymic perimenopausal and early postmenopausal women. Using a randomized, parallel-arm placebo-controlled design, they found that women assigned to placebo were twice as likely to develop clinically significant depressive symptoms compared with those randomized to HT. During 12 months of continuous treatment, 17.3% (n = 15) of those assigned to HT and 32.3% (n = 28) assigned to placebo (P = .03) reported new onset of clinically significant depressive symptoms on the self-reported Center for Epidemiological Studies Depression Scale. The HT regimen used was continuous administration of transdermal estradiol, 0.1 mg/d, plus long-cycle intermittent oral micronized progesterone for 12 days every 3 months. This dose of estradiol is substantially higher than is currently recommended2 for treating bothersome hot flashes, the primary indication for prescribing HT.3 This estradiol dose raises trough concentrations for women who are predominately perimenopausal (approximately 80% of the study population) and intermittently produce ovarian estradiol, but it does not stabilize estradiol concentrations.4
Joffe H, Hickey M. Should Hormone Therapy Be Used to Prevent Depressive Symptoms During the Menopause Transition?. JAMA Psychiatry. 2018;75(2):125–126. doi:10.1001/jamapsychiatry.2017.3945
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