Social isolation and loneliness associate with early menopause and mortality in women: a UK Biobank cohort study

BACKGROUND: Reproductive aging is an emerging public health priority amid demographic shifts. Early menopause (EM), indicative of accelerated reproductive aging, is associated with an elevated risk of premature mortality. While social isolation (SI) and loneliness (LO) are established psychosocial determinants of health, their associations with EM and their combined effects with menopausal status on mortality risk remain unquantified. This study investigated the associations of SI and LO with EM and all-cause mortality. METHODS: This study included 79,578 Caucasian women from the UK Biobank cohort, of whom 6,778 experienced EM (menopause at age 40-45) and 72,800 experienced normal menopause (NM, age 46-55). SI (score: 0, 1, ≥2) was derived from three indicators: living arrangement, frequency of social contact, and participation in social activities; LO (score 0-2) was assessed based on self-reported loneliness and frequency of confiding in someone close. Multivariable-adjusted models were used to evaluate the odds of EM. All-cause mortality risk was assessed using Cox proportional hazards models, stratified by menopause status. RESULTS: Higher levels of SI and LO were independently associated with an increased prevalence of EM (e.g. SI ≥ 2: OR = 1.09, 95% CI 1.00-1.20; LO = 2: OR = 1.13, 95% CI 1.02-1.25). Critically, the detrimental impact of social adversity on survival was significantly greater in women with EM compared to those with NM. After full adjustment, women with EM and SI index ≥ 2 had a 55% increased mortality risk (HR = 1.55, 95% CI 1.21-1.99), whereas the risk increase for women with NM was 17% (HR = 1.17, 95% CI 1.07-1.28). A similar pattern was observed for LO (e.g. LO = 2, EM: HR = 1.42, 95% CI 1.07-1.88 vs. NM: HR = 1.14, 95% CI 1.02-1.27). Moreover, Kaplan-Meier curves showed a progressively wider survival gap between EM and NM as SI/LO levels increased. Lower SI and LO were associated with lower EM-related excess mortality. CONCLUSIONS: SI and LO were associated with EM and premature mortality. Women with EM are especially vulnerable to the negative effects of social adversity. Integrating psychological and social support into menopause care is essential, and reducing SI and LO may promote healthier aging. TRIAL REGISTRATION: NA.