Menopause-associated gut microbiome remodeling and pharmacomicrobiomics: emerging mechanisms influencing drug response

Menopause is accompanied by profound hormonal changes that alter the composition and function of the gut microbiome, potentially influencing microbial drug metabolism and therapeutic response. At the same time, medication use increases substantially during midlife, creating a dynamic bidirectional relationship in which medications modify the gut microbiome while microbiome remodeling may influence medication efficacy, toxicity, and interindividual differences in drug response. This narrative review examines current evidence linking menopause-associated changes in the gut microbiome with medication response and explores the biological mechanisms that may underlie these interactions. The review summarizes microbiome-mediated pathways including microbial β-glucuronidase activity, direct microbial drug metabolism, altered bile acid metabolism, microbial metabolite signaling, and changes in intestinal barrier function and immune regulation that may influence pharmacokinetics and pharmacodynamics. Although direct evidence connecting menopause-associated microbiome remodeling with altered drug response remains limited, substantial evidence supports independent effects of menopause on the gut microbiome and of the gut microbiome on drug metabolism. Together, these findings provide a conceptual framework for understanding how menopause-associated microbial changes may contribute to variability in pharmacotherapy and highlight important priorities for future research, including incorporation of menopausal status into pharmacokinetic studies and clinical trials to advance microbiome-informed precision medicine for women.