From the Journals

Hormone therapy may reduce depressive symptoms in early menopause


Key clinical point: Transdermal hormone therapy may reduce the likelihood of depressive symptoms in early menopause.

Major finding: Women who did not receive hormone therapy had more than a twofold higher likelihood of high depression scores, compared with women who were treated with transdermal estradiol.

Data source: Placebo-controlled, double-blind, randomized trial of 172 perimenopausal women.

Disclosures: The study was supported by the National Institutes of Health, and one author was supported by a fellowship of the Fonds de la Recherche du Québec–Santé. No conflicts of interest were declared.

Source: Gordon JL et al. JAMA Psychiatry. 2018 Jan 10. doi: 1010/jamapsychiatry.2018.3998.


The authors of this study are to be commended for conducting this randomized controlled trial to investigate the efficacy of a biologically rational strategy to prevent depressive symptoms in menopausal women, Hadine Joffe, MD, and Martha Hickey, MD, wrote in an accompanying editorial (JAMA Psychiatry. 2018 Jan 10. doi: 10.1001/jamapsychiatry.2017.3945).

The mechanisms of depression in menopause are not well understood, but increased changes in estradiol concentrations, nocturnal hot flashes, and sleep disturbance have been linked to the emergence of depressive symptoms. However, this study did not report accurate measures of hot flashes and sleep disturbance, which is important because of the central role of those symptoms in menopause associated mood disturbance.

Using hormone therapy in an effort to prevent depressive symptoms throughout perimenopause must be balanced with the adverse effects associated with extended exposure to hormone therapy, such as breast cancer. The results of this trial illustrate a potential role of hormone therapy in mood regulation, but they do not support changes in clinical guidance.

Dr. Joffe is affiliated with the Connors Center for Women’s Health and Gender Biology at Brigham and Women’s Hospital, the department of psychiatry at the hospital, and Harvard Medical School, all in Boston. Dr. Hickey is affiliated with the department of obstetrics and gynaecology at The University of Melbourne. Dr. Joffe was supported by the National Institute on Aging, and she declared research funding and consultancies from private industry, including Merck and SAGE. Dr. Hickey was supported by the Australian National Health and Medical Research Council and had no conflicts of interest to declare.



Hormone therapy may reduce the likelihood of depressive symptoms during early menopause, according to data from a placebo-controlled study published online Jan. 10 in JAMA Psychiatry.

Researchers randomized 172 medically healthy women who were perimenopausal or early postmenopausal to either patches of 0.1 mg of 17 beta-estradiol or placebo patches for 12 months, as well as oral micronized progesterone or placebo every 2-3 months.

Women in the placebo arm were more than twice as likely to score at least 16 on the Center for Epidemiologic Studies–Depression Scale (CES-D) at least once during the study, compared with women in the hormone therapy arm (32.3% vs. 17.3%; odds ratio, 2.5; 95% confidence interval, 1.1-5.7; P = .03). They also scored at least 16 on the scale during more visits than did women in the intervention arm (P = .002).

Women who received placebo had a significantly higher mean CES-D score over the course of the 12-month study, compared with those in the intervention arm. At 6 months, mean unadjusted CES-D scores were 5.6 in the placebo group and 4.2 in the intervention group. At 12 months, the scores were 5.7 and 4 respectively.

“Importantly, these results were significant despite statistically adjusting for change in vasomotor symptom bother, suggesting that TE+IMP [transdermal estradiol + intermittent micronized progesterone] has direct prophylactic mood benefits that are independent from its beneficial effects on menopausal symptoms, as previously observed in women with major depressive disorder treated with TE+IMP,” wrote Jennifer L. Gordon, PhD, of the psychology department at the University of Regina, Saskatchewan, and her associates.

The effect of hormone therapy on depression scores changed significantly depending on the women’s stage of menopause. Women in the early menopause transition experienced significant mood benefits, but women in the late menopause transition and those who were postmenopausal did not.

Treatment effects also were influenced by stress, as women who reported experiencing more stressful life events in the 6 months before enrolling in the study showed greater mood benefits than did those with fewer stressful life events.

However, baseline estradiol levels, baseline vasomotor symptoms, history of depression, and history of abuse did not significantly change the effects of treatment.

Women who received the hormone therapy reported significantly more spotting and bleeding, compared with the placebo group, and one woman in the treatment group experienced acute deep vein thrombosis that led her to stop treatment and receive medical care. Two cases of major depressive disorder were noted in the placebo group.

Dr. Gordon and her associates cited several limitations. For example, they said, the active and placebo patches used in the study were not identical. “However, our findings remain significant when adjusting for participants’ beliefs about their treatment condition,” they wrote.

The study was supported by the National Institutes of Health, and one author was supported by a fellowship of the Fonds de la Recherche du Québec–Santé. No conflicts of interest were declared.

SOURCE: Gordon JL et al. JAMA Psychiatry. 2018 Jan 10. doi: 1010/jamapsychiatry.2018.3998.

Next Article: