The 26th International Symposium on Microsomes and Drug Oxidations

The pharmacological modulation of androgens is a cornerstone of managing conditions ranging from hypogonadism to polycystic ovary syndrome (PCOS). However, a major validation gap currently separates the aggressive marketing of commercial supplements from rigorous evidence-based endocrinology. Our analysis critically synthesizes mechanistic and clinical data for multiple natural products to establish a definitive hierarchy of evidence. We highlight robust randomized controlled trials supporting a restorative rather than stimulatory mechanism for standardized extracts of Withania somnifera (Ashwagandha), Trigonella foenum-graecum (Fenugreek), and Eurycoma longifolia in hypogonadal men, potentially mediated via neuroendocrine modulation of KNDy neurons. Conversely, we validate Mentha spicata (Spearmint) and Curcuma longa as effective anti-androgens that target specific steroidogenic enzymes (CYP17A1). We further dissect the pharmacokinetic barriers that explain the clinical failure of Serenoa repens (Saw Palmetto) in benign prostatic hyperplasia, despite its mechanistic plausibility. By integrating molecular docking, emerging toxicity signals, and clinical efficacy, this meta analysis provides a much-needed scientific framework for the safe integration of phytopharmacology into clinical practice.