Abstract

Although it is well known that women have higher risk of frailty, mechanisms are not clear. Reproductive history may be related to the sex difference in frailty. A total of 1249 community-dwelling women aged ≥60 in England were examined for associations between age at menopause and risk of developing frailty. Frailty defined by the frailty phenotype was measured at baseline and 4 years later. Age at menopause was used as a continuous variable and categorical groups: premature/early (10-45 years), normal (46-55 years), and late (56 years or older). Men with comparable conditions from the same cohort were also used as a comparison. Earlier age at menopause was significantly associated with higher risk of incident frailty. One year later menopause age was associated with a 3% decrease in incident frailty risk (Odds ratio [OR]=0.97, 95%CI=0.95-1.00, p=0.02). Women with premature or early menopause had a significantly higher risk of developing frailty compared with those with normal menopause (OR=1.90, 95%CI=1.28-2.81, p=0.001), while those with late menopause did not. In a supplementary analysis with older men, older women with premature or early menopause were more likely to develop frailty compared with older men (OR=2.29, 95%CI=151-3.48, p < 0.001), however, there was no significant difference between women with normal or late menopause. Earlier menopause was significantly associated with higher risk of developing frailty. Our findings suggest that menopause or its related factors, such as decline in estrogen after menopause, potentially play an important role in the sex difference in frailty.

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