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    Can hormone therapy prevent depression in menopausal women?

    Hormone therapy (HT) can prevent development of depressive symptoms among initially euthymic perimenopausal and early postmenopausal women, according to results of a study published in JAMA Psychiatry. Researchers performed a randomized clinical trial that looked at the efficacy of transdermal estradiol plus intermittent micronized progesterone (TE+IMP) compared to placebo.

    The trial included 172 women aged 45 to 60 who were medically healthy and perimenopausal or postmenopausal. They were self-referred in response to community advertisements. The study used a randomized, double-blind, placebo-controlled design in which the participants were separated into two groups: a TE+IMP and a placebo group. The TE+IMP group was given  0.1mg of 17b-estradiol for 12 months and the placebo group received a placebo patch for the same amount of time. The TE+IMP group also received oral micronized progesterone (200 mg/d for 12 days) every 2 to 3 months. The placebo group received a placebo pill congruent with the TE+IMP schedule. Post-randomization study visits occurred at months 1, 2, 4, 6, 8, 10, and 12. Depressive symptoms were assessed at each study visit during the trial. The symptoms were measured using the Center for Epidemiologic Studies-Depression Scale (CES-D).

    Of the 172 participants, 86 patients were randomized to placebo and 86 patients were randomized to TE+IMP. Sixty-nine patients in the placebo patients and 63 in the  TE+IMP group completed treatment. The mean age of the patients was 51 and 43 patients developed clinically significant depressive symptoms. Women assigned to the placebo group were 32% more likely to develop a clinically significant depressive symptom than women in the TE+IMP group (32.3% vs 17.3%; odds ratio [OR], 2.5; 95% CI, 1.1-5.7; P = 0.03). A baseline reproductive stage moderated the effect of the hormone treatment (b, -1.97; SEM, 0.80, P = 0.03) and women who were in the early stages of menopause saw the greatest mood benefits between TE+IMP and placebo. Women in the late menopausal period (β, −0.9; SEM, 0.3; P = .23) and postmenopausal women (β, −0.3; SEM, 1.1; P = .92) did not have as strong benefits. The researchers also asked participants about stressful life events in the 6 months prior to the study. These events also moderated the effect of treatment on mean CES-D scores so that the mood benefits of TE+IMP increased with the greater number of events (β, 1.22; SEM, 0.40; P = .003).

    The researchers said the strengths of the study were the comprehensive assessment of multiple psychosocial variables, its 12-month duration and bimonthly assessment of symptoms, and the fact that it was the first study to assess TE+IMP as a preventative measure. Weaknesses were identified as infrequent assessments of estradiol before and during treatment and that the active and placebo patches were not identical. The researchers believe the data show that 12 months of TE+IMP therapy is more effective than placebo in preventing clinically significant depressive symptoms among initially euthymic perimenopausal and early postmenopausal women. They note that if the findings are confirmed in future research, clinicians may consider using transdermal HT as a preventative measure to mitigate increased risk of depression during the menopausal transition and early postmenopausal period.

    NEXT: Does prenatal choline exposure promote cognition in infants?

    Ben Schwartz
    Ben Schwartz is Associate Editor, Contemporary OB/GYN.


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