The pharmacological profile of dienogest

Abstract

Dienogest is the first non-alkylated 19-norprogestin on the market. This so-called hybrid progestin combines the typical qualities of the modern 19-norprogestins with those of natural progesterone and synthetic hydroxyprogesterone derivatives. Toxicological investigations have revealed no serious toxic effects in vitro or any short- or long-term experiments in vivo, including carcinogenicity studies. The terminal half-life of dienogest varies between 8 and 10 hours in young cyclic women and between 11 and 12 hours in postmenopausal women (dose linearity for 1–8 mg/day and full absolute oral bioavailability). Progesterone receptor selectivity leads to a specific progestational action without other hormonal or antihormonal side-effects. An important exception in this respect is the antiandrogenic action of dienogest which has been clinically validated. Dienogest shows a strong peripheral progestational and antiproliferative efficacy, mainly on the ovary and uterus, and potent antiproliferative activities against experimental hormone-dependent cancer. The profile of dienogest is such that a specific ‘R&D tree’ may be constructed which extends from new and different approaches for contraception to bleeding-free hormone replacement and from the management of endometriosis to a new opportunity for development for antiproliferative drugs.