Global burden trends and menopause timing associations for gynecological and breast cancers in postmenopausal women

With women aged ≥50 years projected to reach 1.65 billion by 2050, gynecological and breast cancers impose an escalating postmenopausal burden. Whether menopausal timing independently influences cancer risk remains uncertain. We integrated Global Burden of Disease data (204 countries, 1990-2021) with Mendelian randomization and Bayesian projections to evaluate causality and forecast trajectories. Breast and uterine cancer incidence increased (0.17%-0.47% annually), while cervical and ovarian declined, with regional inequalities persisting. By 2040, absolute cases and deaths will surge 60%-129% despite stable age-standardized rates due to population aging. Mendelian randomization using 114 genetic variants from 143,819 women suggests that later menopause increases the risk of breast (odds ratio [OR], 1.24, 95% confidence interval [CI], 1.11-1.39), endometrial (OR, 1.49; 95% CI, 1.23-1.82), and ovarian cancers (OR, 1.23; 95% CI, 1.09-1.39), but not cervical cancer, confirming distinct human papillomavirus (HPV)-driven etiology. Population aging will nearly double cancer deaths by 2040, demanding healthcare expansion, HPV vaccination, and risk-stratified screening.