Progesterone and progestins: applications in gynecology

Achievements obtained in infertility treatments over the past two decades h ave sparked interest in optimizing progesterone administration. Although pr ogesterone is absorbed orally when ingested in micronized form, bioavailabi lity is poor because of extensive liver metabolism. This explains why full predecidual transformation of the endometrium cannot be achieved with oral progesterone and is therefore ineffective for luteal support in in vitro fe rtilization (IVF). Progesterone administered non-orally can duplicate the e ndometrial changes normally seen in the menstrual cycle in women whose ovar ies are inactive. Similar results have been reported with intramuscular (i. m.) injections and vaginal administration, although tissue levels are highe r in the latter case. The recent development of a controlled and sustained release vaginal progesterone gel, Crinone((R)) 8%, has made the vaginal rou te clinically practical by limiting the number of necessary applications to 1 per day. This regimen has been found at least as effective as intramuscu lar (i.m.) injections in women whose ovaries are inactive (donor egg IVF) a nd for luteal support in regular IVF. Hence, painful daily i.m. injections of progesterone in oil become unnecessary. The possibility of reducing the number of daily applications of vaginal progesterone to 1 per day, made pos sible by the sustained release gel Crinone, has opened new possibilities fo r long-term treatments, as in hormone replacement therapy (HRT). The low in cidence of systemic side effects with use of the vaginal progesterone gel u sed for HRT in amenorrheic women, contrasts with findings related to use of synthetic progestins. Preliminary data suggest that vaginal progesterone c an be instrumental in enhancing the notoriously poor long-term compliance o f HRT. (C) 2000 Published by Elsevier Science Inc.