Prospective study of reproductive span and menopausal hormone therapy and cognitive decline over 8 years in the Nurses’ Health Study

Objectives: Higher endogenous estrogen may be associated with better cognition, but associations with menopausal hormone therapy (MHT) have been inconsistent, possibly due to differences in the timing of use. This prospective cohort study aimed to evaluate the associations between reproductive span, as a proxy for endogenous estrogen history, MHT use, and cognitive function. Methods: We assessed cognitive change (1995-2008) with four telephone interviews (primary outcome: global composite score average of six test z -scores) in 14,217 Nurses’ Health Study participants (mean age 74.3 y) and examined associations with reproductive span ([age at menopause]−[age at menarche]), and MHT use duration, separately by 0-10 years, and 11+ years after menopause. Results: A longer reproductive span was associated with better cognitive trajectories (mean annual rate of change difference [95% CI] 41-46 vs. ≤33 y =0.008 [0.00005, 0.015]; P -trend=0.02). MHT use 0-10 years postmenopause was associated with faster decline (mean difference 8-10 vs. 0 y =−0.007 [−0.016, 0.002]; P -trend=0.02); use during 11+ years postmenopause was not associated. Conclusions: Although MHT use was not inversely associated, a longer reproductive span was associated with better cognitive trajectories.