Menopause Accelerates Biological Aging in Liver, Kidneys and Metabolism

Menopause is far more than a reproductive milestone — it appears to be a pivotal inflection point in women's biological aging trajectory. This study, published in BMC Medicine, is among the largest and most comprehensive examinations of how menopausal status, the menopausal transition process, and age at menopause relate to accelerated biological aging across multiple organ systems simultaneously. By drawing on two independent large-scale cohorts — the China Multi-Ethnic Cohort (CMEC, n=37,244) and the UK Biobank (UKB, n=140,479) — the authors were able to test findings across distinct ethnic, geographic, and healthcare contexts, substantially strengthening confidence in the results.

Biological ages were calculated using the Klemera-Doubal Method (KDM), a validated composite biomarker approach that integrates clinical laboratory values and anthropometric measurements into a single biological age estimate. For CMEC, 15 biomarkers were used (including SBP, HbA1c, liver enzymes, renal markers, lipids, and pulmonary function), while 18 biomarkers were used for UKB. These were further organized into four organ-specific biological age scores — cardiopulmonary, metabolic, liver, and kidney — enabling analysis of which organ systems are most affected by menopausal changes. Critically, the study went beyond cross-sectional comparisons by employing longitudinal 'change-to-change' models in sub-cohorts with repeat data (CMEC: n=3,441; UKB: n=1,826), directly measuring how biological age changes as women transition through menopause.

In cross-sectional analyses, compared to pre-menopausal women, those who were peri-menopausal, post-menopausal, or had undergone oophorectomy or hysterectomy all showed significantly greater biological age acceleration across comprehensive, liver, metabolic, and kidney systems. The longitudinal change-to-change models — which control for baseline status and reduce confounding — confirmed these findings robustly: women who transitioned from pre- to post-menopause during the study period showed an increase in comprehensive biological age of β=1.33 years (95% CI: 0.89–1.76) in CMEC and β=2.60 years (95% CI: 1.91–3.30) in UKB, compared to women who remained pre-menopausal. Liver biological age showed the most pronounced and consistent acceleration across all menopausal groups and models, pointing to the liver as a particularly vulnerable organ during hormonal transition.

Age at menopause showed a clear dose-response relationship in the UKB dataset: women with menopause before age 40 (premature menopause) showed β=0.69 years of additional biological age acceleration (95% CI: 0.39–0.98), and those with menopause between 40–44 years showed β=0.24 years (95% CI: 0.09–0.40), compared to those with menopause at 50–54 years. Surgical menopause through oophorectomy was also associated with accelerated aging, consistent with abrupt estrogen withdrawal. Reproductive history factors — specifically younger age at first live birth and higher number of live births — emerged as significant modifiers of the menopause–aging relationship, though the mechanisms remain to be fully elucidated.

The findings carry important implications for both public health and clinical practice. The menopausal transition period — not just post-menopause — appears to be when biological aging accelerates most, suggesting it is a critical intervention window. Women with early menopause are at disproportionate risk. The liver-specific aging signal is particularly notable given the liver's central roles in lipid metabolism, glucose regulation, and detoxification, all of which are influenced by estrogen. Clinicians monitoring menopausal women should consider tracking liver-related biomarkers alongside traditional cardiovascular and bone health markers. The role of hormone replacement therapy and other interventions during perimenopause merits further investigation in this context.