New selective estrogen and androgen receptor modulators.
OBJECTIVE
The present review focuses on the most significant recent findings regarding selective estrogen receptor modulators (SERMs) and selective androgen receptor modulators (SARMs). SERMs, which interact with estrogen receptor-alpha and estrogen receptor-beta in multiple tissues, continue to generate clinical interest in potential applications in as many disorders as the tissues in which the two known receptors are found. SARMs have been demonstrated to have fewer clinical applications to date, but continue to be investigated for use in multiple disorders in which androgen receptor modulation is likely to be important. Both types of compounds hold great promise for therapeutic use in multiple hormonal disorders involving tissue-specific effects mediated by estrogen or androgen receptors.


RESULTS
Although SERMs have been available for clinical use for 50 years, recent investigation has focused on large randomized clinical trials for newer indications of older agents or smaller clinical trials of newer agents with improved clinical activity and reduced side effects in specific tissues. In particular, the large, prospective, randomized, controlled, multiyear Study of Tamoxifen and Raloxifene and Raloxifene Use in the Heart clinical trials have recently shown interesting similarities and differences between tamoxifen and raloxifene in estrogen-responsive tissues. Lasofoxifene and arzoxifene are two newer SERMs that have recently been demonstrated to improve bone mineral density and lower serum cholesterol values compared with older SERMs in smaller clinical trials. SARMs are a newer category of drug still being investigated mostly at the basic and preclinical level, with fewer clinical trials available for review. SARMs are currently being investigated mostly for use in prostate cancer at different stages but hold promise for multiple other applications.


CONCLUSIONS
Recent clinical trials indicate that SERMs are useful in treatment of disorders of bone and mineral metabolism and breast cancer and in reduction of cardiovascular risk factors. SARMs offer important benefits for management of prostate cancer at different stages, as well as other disorders.
Clarke
Bart L
BL
Mayo Clinic W18-A, Rochester, Minnesota 55905, USA.
Khosla
Sundeep
S
D000726:Androgen Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D001851:Bone Diseases, Metabolic / Q000188:drug therapy; D001943:Breast Neoplasms / Q000188:drug therapy; D002318:Cardiovascular Diseases / Q000188:drug therapy; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data; D005260:Female; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy; D011944:Receptors, Androgen / Q000187:drug effects* / Q000378:metabolism; D011960:Receptors, Estrogen / Q000187:drug effects* / Q000378:metabolism; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology* / Q000627:therapeutic use
D000726:Androgen Antagonists; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D020845:Selective Estrogen Receptor Modulators