Effects of Hormone Therapy on Cognition and Mood in Recently Postmenopausal Women: Findings from the Randomized, Controlled KEEPS-Cognitive and Affective Study.
Level 2 - randomized trial
Individual randomized, double-blind, placebo-controlled trial
PubMed 26035291 · doi:10.1371/journal.pmed.1001833
What was done
An ancillary study (KEEPS-Cog) of the multicenter, randomized, double-blind, placebo-controlled Kronos Early Estrogen Prevention Study evaluated 693 recently postmenopausal women (mean age 52.6 years, mean 1.4 years post-menopause). Participants were randomized to: (1) oral conjugated equine estrogens (o-CEE, 0.45 mg/day) plus cyclical oral micronized progesterone (m-P, 200 mg/day for 12 days/month; n = 220); (2) transdermal estradiol patch (t-E2, 50 μg/day) plus cyclical m-P (n = 211); or (3) matched placebos (n = 262) for up to 4 years. Primary outcomes were cognitive function (Modified Mini-Mental State Examination and four domain-specific cognitive composite scores) and mood (Profile of Mood States [POMS]), analyzed using linear mixed-effects models.
What was found
Cognitive outcomes showed no significant treatment-related benefits or harms for either hormone therapy regimen compared to placebo across a mean follow-up of 2.85 years (SD = 0.49). For mood outcomes (mean follow-up 2.76 years, SD = 0.57), o-CEE significantly improved depression scores (model estimate -0.0536, 95% CI -0.0827 to -0.0244; effect size [ES] = 0.49, p < 0.001) and anxiety scores (model estimate -0.0301, 95% CI -0.0509 to -0.0093; ES = 0.26, p < 0.001) relative to placebo. Transdermal estradiol demonstrated no significant differences in mood compared to placebo.
Why it matters
Unlike in women over 65, initiating menopausal hormone therapy in early postmenopause showed no adverse or beneficial effects on cognition over roughly 3 to 4 years, though oral conjugated estrogens provided modest improvements in mood symptoms.
Limits
Loss to follow-up by month 48 was 24.4% for cognitive and 22.8% for mood assessments (mitigated by linear mixed-effects modeling). Mean follow-up was under 3 years, findings cannot be extrapolated beyond 4 years of treatment, and results apply only to recently postmenopausal women with low cardiovascular risk.