Abstract
OBJECTIVE: This study examines the association between the timing of menopause and hysterectomy and biological aging, focusing on epigenetic and physiological aging markers. METHODS: Data were analyzed from women aged 56 and over in the nationally representative Health and Retirement Study (HRS). Regressions of biological aging measured by accelerated epigenetic aging and biological age based on physiological dysregulation on menopause/hysterectomy history were conducted to examine associations of normal-aged and early menopause with and without hysterectomy with biological aging. RESULTS: Hysterectomy, whether following normal-aged or early menopause, or in younger ages, was significantly associated with markers of accelerated biological aging. Women with early menopause or hysterectomy showed accelerated epigenetic aging. Early menopause was associated with accelerated physiological dysregulation only when combined with hysterectomy, suggesting that surgical menopause may be related to accelerated systemic aging processes. Epigenetic clocks were associated with early cellular and molecular aging changes linked to natural early menopause, while physiological dysregulation was associated with the cumulative systemic impacts related to hysterectomy. CONCLUSIONS: This study highlights associations between reproductive history and biological aging. These findings underscore the importance of considering both natural and surgical factors in menopause in evaluating aging-related health risks and suggest avenues for targeted interventions to mitigate health risks in women with these reproductive histories.