Use of oral contraceptives, HRTs may prevent cognitive impairment in women

Shorter reproductive years and greater parity appear to increase the risk of cognitive impairment in late life among Singaporean Chinese women, while the use of oral contraceptives and hormone-replacement therapy (HRT) may reduce such risk, according to a study.

“As the population ages, understanding how these 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 researchers said.

This study included 8,222 women from the Singapore Chinese Health Study, which recruited participants aged 45–74 years between 1993 and 1998. Eligible women were those 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 (2006–2010) interviews, and had had their cognitive function evaluated at ages 61–96 years using the Singapore Modified Mini-Mental State Examination during the follow-up 3 visits (2014–2016).

The researchers used multivariable logistic regression models to estimate odds ratios (ORs) and 95 percent confidence intervals (CIs) for the risk of cognitive impairment.

Compared with women who experienced menopause at age 50–54 years, the ORs for those who had their menopause before 45 years, at 45–49 years, and after 54 years were 1.67 (95 percent CI, 1.32–2.11), 1.24 (95 percent CI, 1.08–1.44), and 1.06 (0.87–1.29), respectively. Compared with women who had 35–39 reproductive years from menarche to menopause, those with <35 reproductive years saw a 28-percent higher risk of cognitive impairment (OR, 1.28, 95 percent CI, 1.11–1.48). [Am J Obstet Gynecol 2020;223:410.E1-410.E23]

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

“To our knowledge, only two cross-sectional studies have examined the relationship of the reproductive period with cognitive function among Chinese women, and both reported that longer reproductive period was significantly associated with better cognitive function,” they added” [J Alzheimers Dis 2016;49:139-147; Psychoneuroendocrinology 2011; 36: 864-873]

Moreover, women who had more than five children had a 27-percent increased risk of cognitive impairment (OR, 1.27, 95 percent CI, 1.04–1.55) compared with those who had one or two children, and this risk increased substantially by 5 percent per child birth (OR, 1.05, 95 percent CI, 1.01–1.09).

On the other hand, women with short-term use (≤5 years) of oral contraceptives had lower odds of having cognitive impairment (OR, 0.74, 95 percent CI, 0.63–0.87) than those who had never used oral contraceptives, but the association was not statistically significant for those who used contraceptives for more than 5 years (OR, 0.87, 95 percent CI, 0.68–1.13). In addition, women who used HRT had a reduced likelihood of having cognitive impairment compared with nonusers (OR, 0.61, 95 percent CI, 0.46–0.80).

“Due to the potential systematic bias and residual confounding in the observational studies, further studies, particularly randomized controlled trials, are needed to determine whether HRTs have protective effects on women’s neurocognitive outcomes, and the timing of treatment that gives greatest neuroprotective benefits to postmenopausal women,” the researchers said.