Menopausal hormone therapy and frailty risk: a nationwide Korean target trial emulation study
Year: 2026
Type: article
Study design: Observational Study
Abstract: Background Menopause is associated with functional decline, but evidence linking menopausal hormone therapy (MHT) to frailty risk remains limited. Aims To evaluate whether achievement of a prespecified MHT exposure threshold was associated with lower frailty risk among MHT initiators. Methods Using the NHIS-HEALS database (2002–2019), we conducted a nationwide new-user cohort study of 31,294 women aged ≥ 45 years who initiated systemic MHT and were non-frail at baseline, with up to 10 years of follow-up. The outcome was transition to high frailty risk status (Hospital Frailty Risk Score [HFRS] > 15). The target strategy was ≥ 28 cumulative days of MHT within 60 days of initiation. Strategies were compared by clone–censor–weighting within a target trial emulation framework, with doubly robust estimation. Results Overall, 25,907 participants (82.8%) achieved the target strategy, which was associated with a lower risk of transition (aHR, 0.88; 95% CI, 0.85–0.92; adjusted 10-year risk difference, − 3.7%; 95% CI, − 4.7 to − 2.8). The association was more pronounced among women aged ≥ 50 years and those with intermediate baseline frailty risk (HFRS 5–15; aHR, 0.77), and differed by formulation (tibolone, aHR 0.63; estrogen-only therapy, aHR 0.94). Discussion The outcome was based on a claims-derived frailty risk score, and because both groups comprised MHT initiators, the findings reflect early adherence rather than MHT use versus non-use. Conclusions Achievement of the specific early MHT exposure threshold was associated with lower transition to high frailty risk status.
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,490
OpenAlex ID: W7225313000