Dienogest—A new progestin

Abstract

Oral contraceptives have over 70 million users world-wide and are regarded as one of the most reliable forms of contraception, but unfortunately their full potential is not yet completely realized. Many women associate long-term oral contraceptive usage with health problems, and experience inadequate cycle control and nuisance side-effects, that often result in non-compliance and treatment discontinuation. Although reduction of the estrogen content has improved safety, new, more selective progestins and different estrogen/progestin ratios may offer greater benefits in terms of both efficacy and safety.Recent advances to combine the desirable activities of both 19-norprogestins and C21-progestins, and develop a hybrid progestin, have led to the introduction of dienogest. Unlike other 19-norprogestin derivatives, dienogest has a substituted cyanomethyl group in place of an ethinyl group at position 17α and, as a result, has a unique endocrinopharmacological profile. Dienogest demonstrates high specificity to the progesterone receptor, with no estrogenic, antiestrogenic or androgenic effects. The peripheral selectivity of dienogest for the progesterone receptor implies that its hepatocellular potency will be less than that of both conventional 19-norprogestins and C21 -progestins. Furthermore, dienogest has potent antiandrogenic activity, with no affinity for sex hormone binding globulin and, as a consequence, does not alter endogenous testosterone levels.The combination of dienogest and ethinylestradiol offers excellent contraceptive reliability and cycle control with a well-tolerated side-effect profile, essential to encourage treatment compliance. Furthermore, its strong progestational effect on the endometrium and antiproliferative efficacy suggest that dienogest would be an attractive alternative progestin for targeted continuous hormone replacement therapy without the need of a withdrawal bleed.