Menopausal Hormone Therapy Slows Cognitive Decline in Postmenopausal Women

Menopausal hormone therapy may slow cognitive decline in postmenopausal women with mild cognitive impairment.

Menopausal hormone therapy (MHT) may slow cognitive decline in postmenopausal women with mild cognitive impairment, according to a recent study published in Menopause.

A team of investigators from Samsung Medical Center, in Seoul, Korea, evaluated the therapeutic effect of MHT using percutaneous estradiol gel and micronized progesterone in women with mild cognitive impairment.

Thirty-seven postmenopausal women with the amnestic subtype of mild cognitive impairment were enrolled in a 24-month prospective, randomized, double-blind trial. All participants received donepezil 2.5 mg/d for the first week; the dosage was then doubled for the next 4 weeks to a maximum of 10 mg/d, if well tolerated. Participants were then randomly assigned to received either MHT (n=19) or placebo (n=18). Percutaneous 0.1% estradiol gel was applied to the forearm before sleep at a starting dosage of 0.5 mg/d and escalated monthly up to a maximum of 2 mg/d, if well tolerated. All participants received oral micronized progesterone 100 mg/d after 3 months.

General cognitive function — measured every 6 months using the modified Alzheimer’s Disease Assessment Scale, cognitive subscale (ADAS-Cog), the Korean version of the Mini-Mental State Examination (K-MMSE), and the Korean version of the Montreal Cognitive Assessment (K-MoCA) — was the primary end point.

Of the initial 37 participants, 21 completed the study (placebo n=13, MHT n=8). Progression rates to dementia were 52.9% in the placebo group and 44.4% in the MHT group. Significantly worse scores were seen in the placebo group for all 3 cognitive assessment tests.  K-MMSE (3.26; 95% CI, 0.04-6.48; P =.0319) and K-MoCA (3.85; 95% CI, -0.46 to 8.16; P =.043) were significantly better at 24 months in the MHT group compared with placebo. ADAS-Cog scores showed no change.

Overall, adverse effects were more frequent in the MHT group than the placebo group.

“Our study shows that long-term MHT using percutaneous [estradiol] gel and oral micronized progesterone might attenuate cognitive decline in postmenopausal women with MCI,” concluded the authors.

In an email interview with Endocrinology Advisor, JoAnn V. Pinkerton, MD, executive director of the North American Menopause Society and a professor of obstetrics and gynecology at the University of Virginia Health System in Charlottesville, explained the significance of these findings.

“As women age, their risk of heart disease, stroke, blood clots and dementia increases,” Dr Pinkerton stated. “Therefore, right now risks appear to be greater than benefits for women over 60 or 70 to start hormone therapy. There is some evidence that transdermal estrogen and micronized progesterone might have less blood clot and stroke risk.”

She noted that currently MHT is not indicated in the prevention or treatment of dementia, but that researchers in the field continue to be intrigued by the “critical window” theory that estrogen administered during menopause may have benefits later.

Related Articles

Dr Pinkerton also noted that the women diagnosed with mild cognitive impairment in this study were concurrently taking donepezil and that “larger trials are needed to evaluate whether [a] cholinesterase inhibitor is needed for effect.”


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