Long-term menopausal hormone therapy may reduce cognitive deterioration in postmenopausal women with mild cognitive impairment, according to a study published in Menopause: The Journal of The North American Menopause Society.

This randomized, double blind, placebo-controlled study included 37 postmenopausal women who were diagnosed with mild cognitive impairment. The participants were randomly assigned to receive menopausal hormone therapy (n=19) or placebo (n=18) for 24 months. Menopausal hormone therapies administered were daily percutaneous estradiol 2 mg gel and oral micronized progesterone 100 mg. Apolipoprotein E genotyping was also performed, and presence of the e4 allele was not different between the groups. Cognitive function was the primary end point of the study, which was measured using various assessment scales every 6 months.

Baseline scores for all outcome measures were comparable, and of the 37 participants, 21 completed the trial (menopausal hormone therapy 8, placebo 13). Results showed that the placebo group’s cognitive function scores significantly deteriorated over the course of the trial compared with the menopausal hormone therapy group. Adjusting for e4 allele presence, the menopausal hormone therapy group showed significant improvement in the Korean versions of the Montreal Cognitive Assessment and Mini-Mental State Examination, suggesting that menopausal hormone therapy, in fact, had a positive influence on cognition.

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A number of adverse events were reported by participants and, as expected, resulted in a higher drop-out rate for the menopausal hormone therapy group. All adverse events were side-effects typically associated with menopausal hormone therapy, including genital and breast problems. Limitations of the study included a small sample size and administration of donepezil to all women in the study for ethical reasons. Although no additional benefit was reported, synergistic effects of donepezil and menopausal hormone therapy could not be completely dismissed.

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Although differences between the group outcomes were demonstrable from 18 months on, manifesting at 24 months, the study investigators report that long-term menopausal hormone therapy using percutaneous estradiol gel and oral micronized progesterone may slow cognitive decline in postmenopausal women with mild cognitive impairment.


Yoon BK, Chin J, Kim JW, et al. Menopausal hormone therapy and mild cognitive impairment: a randomized, placebo-controlled trial [published online May 29, 2018]. Menopause. doi: 10.1097/GME.0000000000001140