Background <p>The association between cumulative endogenous estrogen exposure across the lifespan, especially considering reproductive events, and women’s cardiometabolic health remain unclear. We aimed to examine the associations between lifetime endogenous estrogen exposure and the risks of diabetes, hypertension, and cardiovascular disease (CVD) among postmenopausal women.</p> Methods <p>We used baseline data from the Regional Ethnic Cohort Study in Northwest China. Reproductive factors were self-reported using a structured questionnaire, and surrogate indicators of estrogen exposures—reproductive lifespan, endogenous estrogen exposure, cumulative gestation duration and other proportional indicators—were calculated. Diabetes, hypertension and CVD were defined based on self-reported physician diagnoses at the hospital. Multivariable logistic regression models were employed to estimate adjusted odds rations (aORs) and 95% confidence intervals (CIs).</p> Results <p>Among 35,498 postmenopausal women (median age 59.0 years [interquartile range: 54.0–65.0], each additional year of reproductive lifespan was associated with lower risks of diabetes (aOR 0.971; 95%CI 0.961, 0.982), hypertension (aOR 0.969; 95%CI 0.962, 0.975) and CVD (aOR 0.954; 95%CI 0.946, 0.962). Similar inverse associations were observed for endogenous estrogen exposure. In contrast, a higher ratio of gestation-to-reproductive lifespan duration was positively associated with increased risks of diabetes, hypertension, and CVD. Multiple incomplete pregnancies were associated with increased diabetes risk, while multiple complete pregnancies were linked to elevated risks of hypertension and CVD.</p> Conclusions <p>Longer exposure to endogenous estrogen was associated with decreased risk of cardiometabolic disease, while a higher burden of gestational events was associated with increased risks. Reproductive history could be considered as an indicator for risk stratification and management of cardiometabolic disease in women.</p>