Agonists/antagonists of steroid receptors and bisphosponates in estrogen replacement therapy: Molecular-chemical basis

Abstract

Agonists of estrogen receptors, such as esters of estradiol, conjugated estrogens and esterified estrogens have been widely used in estrogen replacement therapy. Partial agonists of estrogen receptors, derivatives of triarylethylene such as, tamoxifen and toremifene posses weak estrogen-like effects on endometrium, bone and lipids. Recent advances in molecular pharmacology and estrogen receptors have resulted in the development of selective receptor modulators (SEMSs) that activate the estrogen receptor but that also exhibit tissue-specific estrogen-agonist or -antagonist activity. The first SERM marked is the benzothiophene, raloxifene which was introduced to maintain bone density in controlling osteoporosis postmenopausal women. Bisphosphonates have been used as second-line agents for prevention and treatment of osteoporosis in postmenopausal women.

U supstitucionoj terapiji kod žena koriste se hormoni steroidne strukture/ agonisti ERa i ERp estrogenih receptora: derivati estrana, estri estradiola, metaboliti estardiola - prirodni proizvodi konjugovani estrogeni i polusintetski -esterifikovani estrogeni. Pored agonista u terapiji se koriste i parcijalni agonisti steroidnih receptora, derivati trifeniletilena ili trifeniletana kao što su tamoksifen i toreksifen. Derivat rigidne biciklične strukture-benzotiofena, raloksifen, je selektivni modulator estrogenih receptora, agonista estrogenih receptora u osteoblastima i osteoklastima, a antagonista na estrogenim receptorima uterusa i dojke. U terapiji osteoporoze se koriste hemijski stabilni bisfosfonati kao što su alendronat, risendronat i dr.