A paradigm-shifting perspective published in Aging and Disease reframes hormone replacement therapy from symptomatic relief to a fundamental geroprotective intervention capable of influencing biological aging mechanisms in women. The comprehensive review by Rabinovici et al. proposes that HRT mechanistically addresses all 12 hallmarks of aging and emphasizes that ovarian endocrine decline represents one of the earliest accelerators of biological aging, creating a critical intervention window during perimenopause. Women who initiate HRT within 10 years of menopause onset demonstrate reductions in all-cause mortality, cardiovascular disease risk (up to 50%), Alzheimer’s disease (35%), and bone fractures (50-60%). Despite these benefits and extensive clinical use, the authors argue that HRT remains critically underutilized as a geroprotector and advocate for prospective studies to establish optimal protocols for healthspan extension rather than limiting its role to palliative symptom management.

Citation: Rabinovici J, Oonk H-P, Huang Z, Mirando T, Zhou M, Strauss T, Olari LR, Wilczok D, Maier AB, Bischof E. Perimenopausal Hormone Replacement Treatments as a Geroprotective Approach – Adapting Clinical Guidance. Aging and Disease. 2025. doi:10.14336/AD.2025.1391