Effect of Reproductive History and Exogenous Hormone Use on Cognitive Function in Mid- and Late Life

Objectives: To investigate the association between reproductive history indicators of hormonal exposure, including reproductive period, pregnancy, and use of hormonal contraceptives, and mid- and late-life cognition in postmenopausal women. Design: Analysis of baseline data from two randomized clinical trials: the Women's Isoflavone Soy Health and the Early vs Late Intervention Trial of Estradiol. Setting: University academic research center. Participants: Naturally menopausal women (N = 830). Measurements: Participants were uniformly evaluated using a cognitive battery and a structured reproductive history questionnaire. Outcomes were composite scores for verbal episodic memory, executive function, and global cognition. Reproductive variables included ages at pregnancies, menarche, and menopause; reproductive period; number of pregnancies; and use of hormones for contraception and menopausal symptoms. Multivariable linear regression was used to evaluate associations between cognitive scores (dependent variable) and reproductive factors (independent variables), adjusting for age, race and ethnicity, income, and education. Results: On multivariable modeling, age at menarche of 13 and older was inversely associated with global cognition (P =.05). Last pregnancy after age 35 was positively associated with verbal memory (P =.03). Use of hormonal contraceptives was positively associated with global cognition (P trend =.04), and verbal memory (P trend =.007). The association between hormonal contraceptive use and verbal memory and executive function was strongest for more than 10 years of use. Reproductive period was positively associated with global cognition (P =.04) and executive function (P =.04). Conclusion: In this sample of healthy postmenopausal women, reproductive life events related to sex hormones, including earlier age at menarche, later age at last pregnancy, longer reproductive period, and use of oral contraceptives are positively related to aspects of cognition in later life.