Modulators of androgen and estrogen receptor activity

Tis review focuses on signifcant recent fndings regarding modulators of androgen and estrogen receptor activity. Selective androgen receptor modulators (SARMs) interact with androgen receptors (ARs), and selective estrogen receptor modulators (SERMs) interact with estrogen receptors (ERs), with variable tissue selectivity. SERMs, which interact with both ERα and ERβ in a tissue-specifc manner to produce diverse outcomes in multiple tissues, continue to generate signifcant interest for clinical application. Development of SARMs for clinical application has been slower to date because of potential adverse efects, but these diverse compounds continue to be investigated for use in disorders in which modulation of the AR is important. SARMs have been investigated mostly at the basic and preclinical level to date, with few human clinical trials published. Tese compounds have been evaluated mostly for application in diferent stages of prostate cancer to date, but they hold promise for multiple other applications. Publication of the large STAR and RUTH clinical trials demonstrated that the SERMs tamoxifen and raloxifene have interesting similarities and diferences in tissues that contain ERs. Lasofoxifene, bazedoxifene, and arzoxifene are newer SERMs that have been demonstrated in clinical trials to more potently increase bone mineral density and lower serum cholesterol values than tamoxifen or raloxifene. Both SARMs and SERMs hold great promise for therapeutic use in multiple disorders in which tissue-specifc efects are mediated by their respective receptors.