Reproductive Characteristics, Postmenopausal Obesity, and Cardiovascular Disease Incidence in the Women's Health Initiative.

BACKGROUND: Early menarche, menopause, and short reproductive lifespan are risk factors for cardiovascular disease (CVD), but whether these reproductive characteristics are independently associated with CVD or influenced by obesity is unclear. This study aimed to address this gap. METHODS: Postmenopausal women from the Women's Health Initiative longitudinal cohort study without CVD at baseline (October 1993 to December 1998) and followed through January 2025 were included. Early menarche (<12 years) and menopause (<40 years) were self-reported. Reproductive lifespan was defined as the difference between age at menopause and menarche, with short duration as <35 years. Obesity was defined by baseline waist circumference of ≥88 cm. Cox regression models assessed associations of each reproductive characteristic and incident CVD, adjusting for demographic, lifestyle, medical, and reproductive history. Interactions and mediation of reproductive characteristics and CVD by waist circumference were also examined. RESULTS: Participants (N=119 182) reported an age of menarche and menopause at 12.6±1.5 and 48.2±6.3 years of age, yielding an average reproductive lifespan of 35.6±6.4 years. Over a median follow-up of 12.8 years (interquartile range, 8.1-14.1), 12 731 CVD events occurred (rate=10.4/1000 person-years). Early menarche (hazard ratio [HR], 1.07 [95% CI, 1.01-1.15]), early menopause (HR, 1.22 [95% CI, 1.11-1.35]), and short reproductive lifespan (HR, 1.21 [95% CI, 1.13-1.29]) were associated with CVD incidence. Waist circumference was a significant mediator of early menarche, early menopause, and a short reproductive lifespan. CONCLUSIONS: Younger ages at menarche, menopause, and shorter duration of reproductive lifespan were independently associated with CVD incidence; waist circumference was a significant mediator of associations.