Age at menarche and cardiovascular risk according to menopausal status: a nationwide cohort study

Background and Aims Age at menarche (AAM) reflects early-life endocrine and developmental factors that may influence long-term cardiovascular risk. Although prior studies suggest a non-linear association between AAM and cardiovascular disease (CVD), whether this relationship differs according to menopausal status remains uncertain. We evaluated the association between AAM and incident CVD and examined effect modification by menopausal status. Methods This nationwide population-based cohort included women aged ≥40 years who participated in the 2009 Korean National Health Insurance Service health screening programme. Participants were categorised by AAM (≤12, 12–14, 14–16, and >16 years) and menopausal status. The primary outcome was incident CVD, defined as myocardial infarction (MI) or ischaemic stroke. Secondary outcomes included MI, stroke, and cardiovascular death. Adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) were estimated using multivariable Cox proportional hazards models. Results Among 2,156,271 women, 923,350 were premenopausal and 1,232,921 were postmenopausal. In premenopausal women, later AAM was associated with progressively higher CVD risk (aHR 1.216, 95% CI 1.111–1.331 for 14–16 years; aHR 1.393, 95% CI 1.264–1.536 for >16 years; reference ≤12), with consistent findings for MI and stroke (Figure 1). In postmenopausal women, AAM >16 years was modestly associated with increased CVD risk (aHR 1.079, 95% CI 1.002–1.163), with weaker associations for individual outcomes (Figure 2). Significant interactions were observed between AAM and menopausal status for CVD and MI (p for interaction <0.05). Conclusions Later AAM was associated with an increased risk of CVD, particularly among premenopausal women. These findings suggest that delayed reproductive maturation may serve as an early-life marker of cardiovascular vulnerability and that its impact may vary according to menopausal status.