Certain hormonal, reproductive factors affect late-life cognitive function in women

Women with shorter reproductive years and higher parity are at much greater risk of cognitive impairment in late life, although use of oral contraceptives and hormone replacement therapy (HRT) may mitigate this risk, according to a study from Singapore.

“As the population ages, understanding how these [reproductive and hormonal] factors affect late-life cognitive function in women may help health professionals develop preventive measures targeting lifetime oestrogen exposure from endogenous or exogenous sources,” the authors said.

The analysis included 8,222 postmenopausal women (mean age, 53.4 years at baseline) from the Singapore Chinese Health Study. All participants had complete information on reproductive factors and hormonal therapies at baseline (1993–1998), first follow-up (1999–2004) and second follow-up visits (2006–2010).

Cognitive function evaluation using the Singapore Modified Mini-Mental State Examination (SM-MMSE) during the third follow-up (2014–2016; mean age of the population, 73.6 years) revealed that 1,332 women (16.2 percent) had cognitive impairment. This group of women were older, had lower educational level, less likely to be married, but more likely to be smokers and have chronic diseases compared with those who had normal SM-MMSE scores.

In multivariable logistic regression models, the likelihood of late-life cognitive impairment was significantly higher in women who had menopause at a younger age. The odds ratios (ORs) in reference to women who had theirs at 50–54 years of age were 1.67, 1.24 and 1.06 in those who went through menopause at age <45, 45–49 and >54 years, respectively. Having <35 vs 35–39 reproductive years from menarche to menopause was associated with 28-percent greater odds of having cognitive impairment in late life (OR, 1.28, 95 percent confidence interval [CI], 1.11–1.48). [Am J Obstet Gynecol 2020;doi:10.1016/j.ajog.2020.02.032]

Greater parity was also associated with cognitive impairment during the third follow-up. The OR associated with having >5 vs 1–2 children was 1.27, with the estimate increasing by 5 percent per childbirth (OR, 1.05, 95 percent CI, 1.01–1.09).

Meanwhile, short-term use (≤5 years) of oral contraceptives reduced the odds by 26 percent compared with nonuse (OR, 0.74, 95 percent CI, 0.63–0.87), while the association was not statistically significant for >5 years of use (OR, 0.87, 95 percent CI, 0.68–1.13). A similar protective benefit was observed for HRT use vs nonuse (OR, 0.61, 95 percent CI, 0.46–0.80).

“Our findings are generally consistent with previous studies that have examined the relations of menopause age and reproductive period on cognitive function,” the authors said. [Psychoneuroendocrinology 2016;73:224-243; Neurology 2018;90:E1673-E1681; BJOG 2014;121:1729-1739; J Alzheimers Dis 2013;34:601-608]

“A longer duration of reproductive period indicates a higher lifetime exposure to endogenous oestrogen, thus our study supports the hypothesis for a protective function in the neurocognitive effects of oestrogen,” they added.

The authors noted a need for additional investigation to confirm the effects of oral contraceptives and HRTs on women’s neurocognitive outcomes, as well as the timing of HRT that confers the greatest neuroprotective benefits to postmenopausal women.