Age at Menarche and Its Association with Cardiovascular Disease in Women with Childhood-Onset Type 1 Diabetes (T1D)

Objective: Early and delayed menarche are associated with increased cardiovascular disease (CVD) risk in the general population, but data are limited in type 1 diabetes (T1D). We thus examined the relationship between menarche age and CVD risk in women with childhood-onset T1D, representing the first study to evaluate the association between menarche timing and macrovascular disease risk in this population. Methods: Female participants from the Pittsburgh Epidemiology of Diabetes Complications (EDC) prospective cohort study were categorized by menarche age: early (≤12 years), normal (13-15 years), or delayed (≥16 years). Coronary artery disease (CAD) and major adverse cardiovascular events (MACE) were ascertained through clinical examination and surveys. Cox regression models were constructed to assess the relationship between menarche age and each outcome. Results: At baseline, 320 participants were free of CAD and 319 were free of MACE (mean age, 27.8 years; T1D duration, 19.3 years; and median menarche age, 13 years). During 30 years of follow-up, 37.2% developed CAD and 31.3% MACE. A weak, non-significant, U-shaped pattern was observed between menarche age and both outcomes. In multivariable Cox models, compared with normal menarche, early menarche was significantly associated only with higher CAD risk (HR =1.71, 95% CI: 1.11-2.64); no other significant associations were observed. Conclusion: Among women with childhood-onset T1D, early menarche is associated with increased CAD risk.