PHILADELPHIA -- Menopause-related depression was mitigated with transdermal estradiol (E2) plus progesterone in a randomized trial reported here.
One year of treatment with 0.1 mg of E2 added to 200 mg micronized intramuscular progesterone significantly decreased incidence of clinically significant depressive symptoms compared to those assigned to placebo (17.3% versus 32.3%, P<0.05), according to Jennifer L. Gordon, PhD, of the University of Regina in Saskatchewan, Canada, and colleagues.
Women who were not on hormonal treatment were also more likely to report a score of 16 or greater on the CES-D scale at least once during treatment compared to women on estradiol treatment (OR 5.3, 95% CI 1.8-15.8, P<0.01), presented at the annual meeting of The North American Menopause Society.
A total of 172 perimenopausal or early postmenopausal women, who were medically healthy and without a diagnosis of major depressive disorders, bipolar, or any other psychotic disorder at time of enrollment, were randomized 1:1 to active treatment or placebo. All participants were community-dwelling women ages 45-60 and were not taking any medications to confound cardiovascular or endocrine profiles.
Transdermal estradiol was dosed at 0.025 mg for 2 weeks, then increased to 0.05 mg for 4 weeks, and then remained at 0.1 mg for the rest of the study. This was paired with micronized progesterone at 200 mg, which was administered for 12 days, every 2 to 3 months. The control group was provided placebo patches and pills.
Participants were evaluated seven times during the 12-month study. Depressive symptoms were defined at a rate score of 16 or higher on the Center for Epidemiologist Studies-Depression Scale, and bothersome level of vasomotor symptoms were measured according to the Greene Climacteric Scale.
Beneficial treatment effects of E2 and IMP therapy compared to placebo were seen among early perimenopausal women, but were not seen among postmenopausal women. The authors suggested that one possible underlying mechanism to explain this finding might be attributed to the stabilization of fluctuating estradiol levels.
A significant interaction between treatment and recent stressful life events on depressive symptoms reported by the CES-D scale was also noted. Among women who reported high amounts of stressful life events prior to study inception, CES-D score was significantly lower among the TE+IMP group compared to placebo.
Gordon's group also found that prior history of depression, physical or sexual abuse, and baseline vasomotor symptoms and E2 levels were not significant moderators of the treatment effects.
"If confirmed in future research, clinicians may consider using transdermal estradiol as a prophylactic treatment for depressive symptoms in the menopause transition," Gordon stated during an oral presentation of the findings.
During a Q&A following the presentation, a member of the audience inquired as to why the research group chose such a high dose of estradiol. Gordon replied that 0.1 mg has been found to decrease ovulation in the menopause transition and stabilize the hormonal environment compared to lower doses, and the group aimed to find if stabilization of the environment was tied to improved mood.
The research was supported by two NIH grants.
Gordon reported no conflicts of interest.
