Reproductive Fitness and the Links to Chronic Disease and Systemic Aging.

Abstract

Female reproductive aging is the earliest manifestation of aging in humans, with fertility declining due to reduced oocyte quality well before menopause. Menopause marks the definitive end of reproductive potential and the onset of increased risk for multiple age-related, chronic diseases. Emerging evidence links reproductive disorders, from infertility to widespread gynecological conditions such as polycystic ovarian syndrome, with elevated risks of premature morbidity and mortality. Indeed, it is increasingly evident that even normal reproductive transitions such as puberty, pregnancy, and menopause, act as physiological inflection points that shape long-term systemic health. Yet, fertility continues to be viewed primarily through the prism of procreation, with limited knowledge of the underlying biological mechanisms and scarce clinical focus on its broader health implications. Recent discoveries elucidating the genetic basis of reproductive traits combined with advances in our understanding of fundamental aging mechanisms offer a compelling framework to address these persistent knowledge gaps with far-reaching public-health consequences. This review synthesizes the current knowledge on how reproductive aging, normal reproductive phases and major reproductive dysfunctions influence long-term health trajectories and argues for a shift toward integrated, lifespan-based approaches to reproductive health in research and clinical care.