ANIMAL STUDIES ON THE ENDOCRINOLOGIC PROFILE OF DIENOGEST, A NOVEL SYNTHETIC STEROID

Dienogest is an orally active synthetic steroid that is used for contr aception and is currently being studied for the possible treatment of endometriosis. Earlier we demonstrated that dienogest had therapeutic effects on experimental endometriosis in rats and that its mechanisms of action were different from those of drugs currently on the market f or the treatment of endometriosis. We also reported preclinically that dienogest showed a potential anticancer action against hormone-depend ent cancers that was different from that of progestins. Accordingly we obtained preclinical background data for the above-described clinical applications and extension of the clinical use of the drug in the nea r future by investigating the endocrinological profile of dienogest in rabbits and rats. Dienogest was characterized by having a moderate bi nding affinity for progesterone receptors and by progestational activi ties: it stimulated endometrial proliferation (greater than or equal t o 0.01 mg/kg) that was only partially inhibited by RU-486, and induced carbonic anhydrase activity in endometrium (greater than or equal to 0.01 mg/kg). Also, it was slightly uterotrophic (greater than or equal to 1 mg/kg) with very low binding affinity for oestrogen receptors an d slightly antioestrogenic (greater than or equal to 1 mg/kg). In addi tion, dienogest showed slight binding to androgen receptors but withou t biological androgenic and anabolic activities (100 mg/kg), with neit her glucocorticoid activity nor mineralocorticoid activity (100 mg/kg) , and with very slight binding affinity for human sex hormone-binding globulin. These findings suggest that dienogest is not a pure progesti n and appears to induce fewer side effects than drugs currently on the market for the treatment of endometriosis.