[Preliminary trials of an oral chemical contraceptive for men]. / Premiers essais d'une contraception chimique par voie orale chez l'homme

PIP: R 2323 (13-ethyl, 17 alpha-ethyl, 18-hydroxy-gona-4,9,11-trien-3-one) was administered orally, 50, 75, or 100 mcg/week in 2 or 3 divided doses with or without 3 100 mg testosterone implants to arrest spermatogenesis, to 20 healthy men 25-35 years of age with at least 2 children. There were 3 dropouts, 1 for a high triglyceride level. 7 men became azoospermic within 2-3 months after the combined treatment and 8 after receiving 75 or 100 mg/week of R 2323 only. No abnormal sperm forms appeared. Side effects were weight gain of 2-8 kg chiefly with the combined schedule. Libido declined in 3, erective capacity decreased in 2, and coital frequency fell in 8. 1 case of gynecomastia appeared after 4 months. 1 man had a superficial thrombosis in the left arm at the site of a biopsy for polyadenopathy. Testosterone fell from 5 to .5 ng/ml and follicle stimulating hormone and luteinizing hormone from 5-1 mIU/ml in both groups. The only remarkable change in a biological parameter was an increase in transaminase, especially SGPT, 25-50%. Testosterone and gonadotropins returned to normal within 1 month after stopping steroids, and sperm counts within 3-4 months. The testosterone implants failed to prevent plasma testosterone levels from falling, and seemed to cause more side effects such as weight gain and loss of libido than did R 2323 alone.^ieng

Action of midcycle contraceptive (R 2323) on the human endometrium.

Over 2,148 cycles of midcycle oral administration of R 2323 (50 mg. per day on Days 15,16, and 17), the authors recorded a drug-failure pregnancy rate of 5 per cent and an unusually regular cycle length of 28 +/- 2 days. During this trial, endometrial biopsies obtained in the luteal phase were examined by light and electron microscopy and compared to pretreatment biopsies. Light microscopy indicated a weakly secretory endometrium suggestive of some, albeit low, progesterone impregnation. Ultrastructural examination revealed deleterious changes in the development of the nucleolar channel system and giant mitochondria and a delay in the migration of glycogen granules. This low progesterone impregnation could be explained either by a direct effect of R 2323 on cell ultrastructure or by interference with progesterone availability. It would appear that R 2323 acts as a temporary substitute for progesterone at the receptor level but that it does not induce all the biological manifestations of this hormone, in particular, the endometrial changes required for implantation.