Impact of long-term medication on estrobolome-associated β-glucuronidase and sulfatase activities: Implications for estrogen homeostasis in postmenopausal women.

Menopause leads to a decline in circulating estrogen levels, increasing cardiometabolic risk, contributing to bone loss, and decreasing quality of life. The estrobolome, a subset of microbes with β-glucuronidase (GUS) and sulfatase activities, regulates estrogen homeostasis through deconjugation and enterohepatic recycling, thereby influencing systemic estrogen availability. Common long-term pharmacological treatments in postmenopausal women may alter gut microbial composition and function, potentially affecting estrobolome activity and systemic estrogen levels. This narrative review examines current evidence on how long-term pharmacological treatments may affect estrobolome-associated GUS and sulfatase activities, with implications for estrogen metabolism and health outcomes in postmenopausal women. A targeted literature search was performed to identify clinical studies on commonly prescribed drugs for hypertension, diabetes, dyslipidemia, osteoporosis, and depression in postmenopausal women, focusing on microbial taxa with reported GUS or sulfatase activity. Among the evaluated pharmacological classes, antidiabetic drugs, particularly metformin, are the most extensively studied, followed by antidepressants. These treatments can modulate key gut bacterial genera with GUS and sulfatase activities, including Bifidobacterium, Roseburia, Faecalibacterium, and Clostridium, which are relevant to metabolic and estrogen homeostasis. However, no studies have directly assessed the impact of pharmacological treatments on GUS and sulfatase activity in postmenopausal women. Understanding how chronic medication influences estrobolome dynamics may help identify strategies to support estrogen balance and improve systemic metabolic, hormonal, vascular, and inflammatory profiles. This review highlights the interplay between long-term medication, gut microbiota, and estrogen homeostasis as a promising avenue for personalized microbiota-targeted therapies in postmenopausal health.