One year of transdermal estradiol plus micronized progesterone helped prevent the development of depressive symptoms more effectively than placebo among perimenopausal and early postmenopausal women, according to data published in JAMA Psychiatry.
“Depression risk is known to increase among women in the menopause transition and early postmenopausal period, with rates of major depressive disorder and clinical elevations in depressive symptoms roughly doubling to tripling compared with premenopausal and late postmenopausal rates,” Jennifer L. Gordon, PhD, assistant professor in the department of psychology at the University of Regina in Canada, and colleagues wrote. “A few trials suggest that estrogen therapy, with or without progesterone … is an effective treatment for perimenopausal depression.”
Researchers examined the efficacy of transdermal estradiol plus intermittent micronized progesterone (TE+IMP) in preventing depressive symptoms among initially euthymic perimenopausal and early postmenopausal women aged 45 to 60 years in a double-blind, placebo-controlled randomized trial. For 12 months, patients received daily transdermal estradiol along with oral micronized progesterone (daily for 12 days) every 3 months or transdermal placebo along with identical placebo pills. They assessed depression scores at baseline and months 1, 2, 4, 6, 8, 10 and 12 after randomization, and the incidence of clinically significant depressive symptoms, defined as Center for Epidemiological Studies–Depression Scale (CES-D) score of at least 16.
Of 172 participants, 43 developed depressive symptoms. Women who received placebo had a higher likelihood than those who received TE+IMP of scoring at least 16 on the CES-D during intervention (32.3% vs. 17.3%; OR, 2.5; 95% CI, 1.1-5.7) and had a higher average depression score (P = .03). Researchers reported baseline reproductive stage moderated the effect of treatment (P for the interaction = .03), with mood benefits of TE+IMP compared with placebo among women in the early menopause transition (P < .001), but not the late menopause transition or among postmenopausal women. Furthermore, stressful events in the 6 months prior to enrollment moderated the effect of treatment on average depression score, with mood benefits of TE+IMP increasing with a greater number of events (P = .003). Therefore, TE+IMP may benefit women in the early menopause transition and in women reporting stressful events, the researchers suggest.
“To our knowledge, we are the first to report that TE+IMP administration prevents this transition-related increase in risk for depressive mood,” Gordon and colleagues wrote. “Health care professionals should be alert to the high risk for clinically significant depressive symptoms in this population. If our results are confirmed in a larger sample, clinicians may consider using TE+IMP as a prophylactic treatment in the prevention of clinically significant depressive symptoms in medically eligible perimenopausal and early postmenopausal women.”
Although hormone therapy is an FDA-approved treatment for hot flashes and vaginal dryness, it is not approved for the prevention of mood disturbance — a fact women and their doctors should consider before starting therapy — according to Hadine Joffee, MD, MSc, from the Connors Center for Women’s Health and Gender Biology, and the department of psychiatry at Brigham and Women’s Hospital, Harvard Medical School, and Martha Hickey, MD, MBChB, MSc, from the department of obstetrics and gynecology at the University of Melbourne in Australia, who wrote an accompanying editorial.
“We agree with the authors’ conclusion that more information is needed before [hormone therapy] should be considered for the prevention of depressive symptoms,” Joffee and Hickey wrote. “While results of this randomized clinical trial are provocative and illustrate the potential role of gonadal steroids in the regulation of mood, they do not support a change in clinical guidance for the use of [hormone therapy] in women traversing menopause.” – by Savannah Demko
Disclosures: The authors report no relevant financial disclosures. Joffe reports receiving research funding from Merck and SAGE and is a consultant to Merck, Mitsubishi-Tanabe, NeRRe and SAGE. No other disclosures were reported.