LAUSR

BACKGROUND Epidemiologic studies suggest that declining estrogen level in menopause may play an important role in the pathogenesis of dementia and contribute to increased risk of cognitive impairment in women. Most previous studies have been conducted in Western population to investigate the relations of the length of reproductive periods and use of HRT with risk of cognitive function and dementia, but the findings are inconclusive. Relevant evidence among Asian populations is limited. OBJECTIVES To evaluate the association between reproductive and hormonal factors, and risk of cognitive impairment in Chinese women with natural menopause. STUDY DESIGN The Singapore Chinese Health Study is a population-based study that recruited participants aged 45-74 years between 1993 and 1998, and the current study included 8,222 women from this cohort who had natural menopause, complete data on reproductive factors and hormonal therapies at baseline (1993-1998), follow-up 1 (1999-2004) and follow-up 2 interviews (2006-2010), and cognitive function evaluated at ages 61 to 96 years using the Singapore Modified Mini-Mental State Examination (SM-MMSE) during the follow-up 3 visits (2014-2016). Multivariable logistic regression models were used to estimate odds ratios (ORs) and 95% confidence interval (CI) for the risk of cognitive impairment. RESULTS Compared to women with menopause at 50-54 years of age, the OR (95% CI) were 1.67 (1.32, 2.11), 1.24 (1.08, 1.44), and 1.06 (0.87, 1.29) for women who experienced menopause before 45 years, at 45-49 years of age, and after 54 years, respectively. Compared to women with 35-39 reproductive years from menarche to menopause, the OR (95% CI) were 1.28 (1.11, 1.48) for women with <35 reproductive years. Furthermore, compared with women who had 1-2 children, the OR (95% CI) were 1.27 (1.04, 1.55) for women who had more than 5 children, and the risk increased significantly by 5% per child birth (OR: 1.05; 95% CI: 1.01, 1.09). Compared to those who had never used oral contraceptives, women with short-term use (≤ 5 years) of oral contraceptives had 26% lower odds of having cognitive impairment (OR: 0.74; 95% CI: 0.63, 0.87), while the association was not statistically significant for those used for more than 5 years (OR: 0.87; 95% CI: 0.68, 1.13). Women who used HRT had a 39% lower odd of getting cognitive impairment compared to non-users (OR: 0.61; 95% CI: 0.46, 0.80). CONCLUSIONS Our data suggested that shorter reproductive years and higher parity were associated with higher risk of cognitive impairment in late life, while use of oral contraceptives and hormone replacement therapy were associated with decreased risk. As the population ages, understanding how these factors affect late-life cognitive function in women may help health professionals develop preventive measures targeting lifetime estrogen exposure from endogenous or exogenous sources.