Megestrol acetate

Megestrol acetate, a well-absorbed oral synthetic progestogen, targets progesterone receptor (PR) (~130% progesterone affinity), androgen receptor (AR) (~5% metribolone affinity, antiandrogenic), and glucocorticoid receptor (GR) (~30% dexamethasone affinity). It serves as a potent progesterone receptor (PR) agonist/androgen receptor (AR) antagonist for hormone cancers and cachexia. This dual action supports its use in hormone-sensitive cancers (breast, endometrial, prostate) by inhibiting proliferation and estrogenic effects, and in prostate cancer via potential 5α reductase inhibition. Clinically, megestrol acetate acts as an antiandrogen and potent appetite stimulant, with an unclear mechanism involving Neuropeptide Y. Megestrol acetate’s efficacy in palliative cancer care and cachexia management, sometimes synergistic with tamoxifen, is tempered by potential GR-related side effects.