No cognitive impact 10 years after short-term, early menopausal hormone therapy: KEEPS

Key takeaways:

• Analyses demonstrated no long-term cognitive impact with short-term menopausal hormone therapy use after 10 years.
• Hormone therapy was not protective against cognitive decline.

Short-term exposure to hormone therapy started within 3 years of menopause was not associated with long-term cognitive impairment or benefit, according to data from the KEEPS Continuation study.

Previously, the Kronos Early Estrogen Prevention Study-Cognition (KEEPS-Cog) 2005 to 2008 trial suggested no cognitive benefit or harm after 49 months of menopausal hormone therapy use when initiated within 3 years of final menstruation.

“To clarify the long-term effects of menopausal hormone therapy initiated in early postmenopause, the observational KEEPS Continuation study reevaluated cognition, mood and neuroimaging effects in participants enrolled in the KEEPS-Cog and its parent study the KEEPS approximately 10 years after trial completion,” Carey E. Gleason, PhD, professor in the department of medicine at the University of Wisconsin-Madison and the Geriatric Research, Education and Clinical Center at William S. Middleton Memorial Veterans Hospital, and colleagues wrote.

Gleason and colleagues conducted the KEEPS Continuation study, an observational, longitudinal cohort study of the KEEPS clinical trial, from 2017 to 2022. Researchers contacted 299 participants from seven sites 10 years after conclusion of KEEPS for in-person research visits. Participants repeated the original KEEPS-Cog test battery and researchers assessed cognitive factor and global cognitive scores.

The findings were published in PLOS Medicine.

Overall, 275 participants had data on cognition from both KEEPS and KEEP Continuation available for analysis.

Latent growth models indicated that cognitive factor scores changed over time for all participants and menopausal hormone therapy did not differentially influence cognitive outcomes during use or 10 years after KEEPS-Cog conclusion.

Researchers observed no statistically significant differences when assessing the impact of menopausal hormone therapy on cognition during KEEPS and across all follow-ups, including during KEEPS Continuation. KEEPS Continuation demonstrated no long-term cognitive impact after menopausal hormone therapy use. Participants in the menopausal hormone therapy group had similar cognitive measures after 10 years as those not on hormone therapy.

“Findings may reassure women opting to use hormone therapy in early menopause, to manage menopausal symptoms, that 4 years of therapy started within 3 years of menopause had no long-term deleterious impact on cognition,” the researchers wrote. “Our results also indicate that menopausal hormone therapy does not prevent cognitive decline when initiated around the time of menopause. Therefore, menopausal hormone therapy should not be recommended as a strategy for improving or preserving cognitive function in recently menopausal women with low cardiovascular risk.”