Perimenopausal Hormone Replacement Treatments as a Geroprotective Approach - Adapting Clinical Guidance

The decline in ovarian endocrine function represents a pivotal event in female aging, initiating systemic biological deterioration well before the end of reproductive capacity. We propose that Hormone Replacement Therapy (HRT) may constitute an early stage geroprotective intervention with mechanistic relevance across the 12 hallmarks of aging. Despite extensive clinical use, HRT remains underutilized as a geroprotector. Although there is promising data, prospective, biomarker-driven interventional studies are required to test this paradigm. This narrative review outlines the role of HRT as a geroprotective therapy, preferably offered and started within 10 years of menopause onset, in clinically eligible women in perimenopause. We emphasize the need for specific clinical guidelines that reflect and manage the endocrine, inflammatory, and metabolic profiles unique to perimenopause. The development of age- and phase-specific biomarkers will be critical to optimize HRT use and ensure precision delivery of longevity-focused care for women.