Menopausal hormone therapy and mild cognitive impairment: a randomized, placebo-controlled trial

Objective:The aim of the study was to explore the therapeutic potential of menopausal hormone therapy (MHT) in women with mild cognitive impairment (MCI).Methods:Thirty-seven postmenopausal women (age range: 57-82 y) with multiple-domain, amnestic subtype MCI were randomly assigned to either placebo (n=18) or MHT (n=19) for 24 months (percutaneous estradiol [E-2] gel [0.1%, 2mg/d] and oral micronized progesterone [MP4] [100mg/d]). All participants received donepezil, and apolipoprotein E genotype was determined. The primary endpoint was general cognitive function: Alzheimer's disease Assessment Scale, cognitive subscale, the Korean version of Mini-Mental State Examination (K-MMSE), and the Korean version of the Montreal Cognitive Assessment (MoCA_K) were performed in-person every 6 months.Results:Twenty-one participants (placebo 13, MHT 8) completed the trial (56.8%). Progression rates to dementia were 52.9% (9/17) in the placebo group and 44.4% (8/18) in the MHT group. Within-group analysis showed that all three tests significantly worsened during the trial in the placebo, but not the MHT groups. Analysis adjusted for epsilon 4 allele demonstrated that MHT significantly reduced deterioration of MoCA_K score, a sensitive tool for assessing global cognition in MCI (P=0.0261). Compared with the control group, both MoCA_K (P=0.043; mean difference, 3.85; 95% CI, -0.46 to 8.16) and K-MMSE (P=0.0319; mean difference, 3.26; 95% CI, 0.04-6.48) scores were significantly better at 24 months in the MHT group.Conclusions:Long-term MHT using percutaneous E-2 gel and oral MP4 might attenuate cognitive decline in postmenopausal women with MCI.