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From the Journals

Menopause Treatment Shows No Brain Effects After Decade

Large continuation study challenges 'critical window' hypothesis by showing cognitive performance was unaffected by hormone therapy timing, formulation choice, or duration.

Conexiant

The Kronos Early Estrogen Prevention Study Continuation Study found no long-term cognitive differences between women who received menopausal hormone therapy and those who received placebo, according to new findings.

In the study, published in PLOS Medicine, investigators examined 275 women approximately 10 years following their participation in the original Kronos Early Estrogen Prevention Study (KEEPS) trial. The participants had been randomly assigned to receive oral conjugated equine estrogens (oCEE), transdermal estradiol (tE2), or placebo for 48 months.

The research measured four cognitive domains: verbal learning and memory, auditory attention and working memory, visual attention and executive function, and speeded language and mental flexibility. Global cognition was assessed using the Modified Mini-Mental State examination.

Statistical analysis showed that baseline cognition and cognitive changes during the original KEEPS trial were the primary predictors of later cognitive performance. The analysis controlled for education, age, and APOE ε4 carrier status.

The study population included women who began hormone therapy within 3 years of their final menstrual period. All participants had low cardiovascular risk profiles with no diabetes or prior hysterectomy. The protocol used lower oCEE doses compared with previous studies and administered cyclic micronized progesterone.

The Women's Health Initiative Memory Study (WHIMS), which explored hormone therapy initiated in women aged 65 years and older, reported different outcomes. The KEEPS Continuation Study examined a younger population at the time of treatment initiation.

The study retained 41% of the original cohort, with recruitment occurring partly during the COVID-19 pandemic. The participant group consisted primarily of non-Hispanic White women with higher education levels.

The KEEPS Continuation Study was conducted at seven U.S. clinical sites from 2017 to 2022. The original KEEPS randomized clinical trial registration number was NCT00154180.

Potential competing interests are outlined in the study.