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Globally, women tend to live about five years longer than men but face more chronic diseases post-menopause, raising questions about the health impact of aging and hormonal changes. Estrogen plays a crucial role in health and aging, influencing life stages like pregnancy and menopause. In 2013, IgG glycosylation was identified as a key biomarker of biological age, with its modulation affecting systemic inflammation and predisposing individuals to various age-related conditions. Studies show that perimenopause accelerates aging and inflammation, leading to chronic diseases, but hormone replacement therapy (HRT) can counteract this. Estrogen positively affects the IgG glycome, reducing inflammation, while testosterone replacement therapy (TRT) benefits are mediated through estrogen. Blocking estrogen conversion negates TRT's positive effects. Thus, maintaining healthy estrogen levels through HRT and TRT could be seen as an early approach to enhancing longevity, with precision medicine and glycan biomarkers offering future direction.