Neurology

Age at menopause, estradiol therapy route linked to domain-specific cognitive performance

September 11, 2025

Study details: This cross-sectional observational cohort study analyzed baseline data from 7,251 cognitively normal postmenopausal women (mean age, 60.5 years) in the Canadian Longitudinal Study on Aging. Associations between age at menopause and estradiol (E2)-based menopausal hormone therapy ([MHT], oral vs. transdermal) with performance in episodic memory, prospective memory, and executive functions were assessed using linear regression, adjusting for age, education, and vascular risk.

Results: Earlier age at menopause was significantly associated with lower scores in all cognitive domains (episodic memory, prospective memory, executive functions; all p<0.001). The negative impact on executive function was most pronounced in women with ≥4 children and among APOE ε4 carriers. Transdermal E2 use was associated with higher episodic memory scores (Cohen d = 0.303, p = 0.007), while oral E2 was associated with higher prospective memory scores (Cohen d = 0.283, p = 0.015). Neither route significantly affected executive functions.

Clinical impact: Findings suggest earlier menopause is a risk factor for cognitive decline across multiple domains, and E2-based MHT may confer domain-specific cognitive benefits depending on administration route. Precision in MHT selection (transdermal for episodic memory, oral for prospective memory) may optimize cognitive outcomes in postmenopausal women, though causality cannot be established from this observational data.

Source:

Puri TA, et al. (2025, September 23). Neurology. Association Between Menopause Age and Estradiol-Based Hormone Therapy With Cognitive Performance in Cognitively Normal Women in the CLSA. https://pubmed.ncbi.nlm.nih.gov/40865026/