ORGAN TARGETING WITH THE ORAL PROGESTIN DIENOGEST

In oral contraceptives, progestins are added to estrogens for ovulatio n inhibition and regular withdrawal bleeding, whereas in hormone repla cement therapy (HRT) progestins are responsible for prevention of endo metrial hyperplasia. Unfortunately, the coadministration of progestins may reduce the beneficial effects of estrogens on bone, cardiovascula r and nervous system. Additionally, progestins may stimulate prolifera tive processes in the mammary gland. The present paper presents result s of experimental and clinical studies demonstrating differential orga n-specific effects of the new progestin dienogest (17 alpha-cyanomethy l-17 beta-hydroxy-4,9-estradien-3-one). After oral administration, die nogest acts mainly on the ovary and uterus. Ovulation inhibition in cy cling women was achieved without significant alterations of gonadotrop in secretion. When compared with other progestins such as levonorgestr el, desogestrel and chlormadinone acetate, dienogest displayed the hig hest quotient between doses necessary for ovulation inhibition (antigo nadotropic) and endometrium transformation (uterotropic). In a regimen of continuous combined HRT, consisting of 17 beta-estradiol plus diff erent doses of dienogest, the pattern of histomorphological changes in the endometrium showed a clear dose-dependence, demonstrating pronoun ced action of dienogest on the endometrium. Different parameters of ca rdiovascular system such as serum lipids and endothelial and smooth mu scle function were not affected by this progestin. In several in vitro and in vivo assays, dienogest showed antiproliferative activities tha t were not related to its progestagenic potential. Thus, dienogest is a promising candidate for a progestin with organ targeting activity th at can be used as a constituent of well tolerated and safe oral contra ceptives and preparations for HRT.