Earlier Menopause is Associated With Higher Risk of Incident Frailty in Community-Dwelling Older Women in England

Gotaro Kojima PhD; Yu Taniguchi PhD; Reijiro Aoyama PhD; Tomohiko Urano MD, PhD


J Am Geriatr Soc. 2022;70(9):2602-2609. 

In This Article

Abstract and Introduction


Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.


Frailty is a medical condition of vulnerability to poor resolution of homeostasis after a stressor event and age-related decline in many physiological systems.[1,2] Frail older adults are predisposed to adverse health outcomes, including falls,[3] fractures,[4] disabilities,[5] hospitalization,[6] and nursing home placement,[7,8] and have substantially high mortality risk.[9] Previous studies have consistently shown that women are frailer than men in all age groups and in different populations.[10]

Although the mechanism of the sex gaps in frailty risk has not been completely clarified, several biological, behavioral, and social factors are considered to potentially explain the sex differences in frailty.[11] For example, inflammation seems to play an important role in the pathophysiology of frailty,[12,13] more in women than in men due to more accumulated abdominal fat in women.[14] Other frailty risk-related behaviors, such as smoking or drinking,[15–17] may put greater risks of related morbidity and mortality as well as frailty on women than men.[18,19] In addition, women may be more vulnerable than men because of social factors, such as living situation[20] or marital status.[21] Among the potential contributors, reproductive history is unique to women and may be related to the sex difference in frailty.[22] Menopause is associated with a drastic decline in sex hormones, which could negatively affect women's health and possibly increase their risk of frailty.[23] In fact, women who experienced menopause earlier in life (before age 45) have been shown to have increased risks of overall mortality, cardiovascular diseases, and neurological diseases.[24] However, there is limited evidence of associations between menopause and frailty; only two cross-sectional studies were found in the literature, providing inconsistent findings.[25,26] Further attempts to explore associations between menopause and frailty would shed light on underlying mechanisms of sex disparity in frailty. Therefore, the objective of this study was to examine the associations between age at menopause and subsequent risk of developing frailty over 4 years in community-dwelling postmenopausal older women.