Selective Estrogen Receptor Modulators (SERMs) in non-cancer therapeutics: expanding horizons beyond oncology

Selective Estrogen Receptor Modulators (SERMs) represent a class of compounds that demonstrate tissue-specific agonist or antagonist activity on estrogen receptors, allowing for selective modulation of estrogenic effects across different tissues. Originally developed for the treatment of hormone receptor-positive breast cancer, SERMs have revealed significant potential for use in non-cancer therapeutics due to their diverse pharmacological profiles. This review thoroughly examines the expanding applications of SERMs beyond oncology, elaborating on their mechanisms of action, pharmacokinetics, and clinical applications.

Compounds such as raloxifene, bazedoxifene, tamoxifen, and lasofoxifene have proven effective in managing osteoporosis by enhancing bone mineral density and reducing the risk of fractures. Moreover, their cardiovascular benefits include improved lipid profiles and endothelial function, albeit with an awareness of associated thromboembolic risks. SERMs also display neuroprotective properties, suggesting potential advantages in cognitive disorders such as Alzheimer's disease, in addition to alleviating menopausal symptoms through tissue-selective estrogen complex therapies.

A comparative analysis reveals variations in efficacy, safety, and tissue selectivity among the different SERMs. Despite their therapeutic potential, challenges such as thromboembolic risks, inconsistent patient responses, and adverse effects demand careful clinical consideration. Future efforts will focus on developing next-generation SERMs that offer improved tissue selectivity, reduced side effects, and personalised treatment strategies informed by pharmacogenomic insights. This review emphasizes the necessity for continued research to broaden the therapeutic landscape of SERMs, highlighting the importance of balancing efficacy and safety to optimize patient outcomes across various non-cancer conditions.