Public Health

Early menopause (EM) is a potential risk factor for cognitive impairment, yet its impact remains underexplored in low- and middle-income countries, where modifiable risk factors play a key role in dementia development. This study investigates how EM, hormone therapy (HT), and reproductive lifespan influence cognitive outcomes in Brazilian women.

Data were analyzed from 4,316 postmenopausal women (≥50 years) in the Brazilian Longitudinal Study of Aging (ELSI-Brazil). EM was defined as onset before 45 years. Cognitive performance was assessed via a global cognitive score (GCS), calculated from Z-scores of five cognitive subdomains: orientation, fluency, episodic memory, semantic memory, and prospective memory. Covariates included age, previous stroke, and modifiable dementia risk factors: education, depression, sensory deficits, and metabolic factors. Linear regression modeled GCS, while logistic regression estimated the odds of cognitive impairment (GCS ≤ -1.5 SD). Subgroup analyses stratified women by EM and HT use. T-tests and chi-squared tests were used when appropriate. All statistical analyses were performed in R, with p < 0.05 considered statistically significant.

Baseline characteristics of EM (n = 1,217) and regular menopause (n = 3,099) groups are displayed in Table 1. EM was independently associated with lower GCS (β: -0.04, p = 0.03), while years of menacme (β: 0.004, p = 0.02) were protective. HT was not significantly associated with GCS (β: 0.04, p = 0.08) (Table 2). EM increased the odds of cognitive impairment (OR: 1.38, 95% CI: 1.09-1.76) (Figure 1). Subgroup analyses showed EM/HT- had significantly lower GCS than EM/HT+ (β: -0.09, p < 0.01), while EM/HT+ was comparable to regular menopause groups (p = 0.43) (Table 2). Moderation analysis confirmed a significant interaction between HT and EM (β: 0.11, p = 0.02), suggesting HT attenuates EM's negative impact.

EM is an independent risk factor for cognitive impairment, while a longer reproductive lifespan appears to be associated with cognitive health. The interaction between EM and HT highlights HT's potential to mitigate cognitive decline, supporting EM as a modifiable sex-specific risk factor for cognitive impairment.