[Effects of an anti-progestin steroid in women: interruption of the menstrual cycle or early pregnancy (author's transl)]. / Effet d'un steroide anti-progesterone chez la femme: interruption du cycle menstruel et de la grossesse au debut.

PIP: The 19-nor steroid, RU-486, has an affinity for progestin receptors, and is also a progesterone as shown in animal studies. RU-486 was administered orally in a dose of 200 mg a day for 4 consecutive days to 11 women aged 18-34 seeking 1st trimester abortion. Bleeding occurred, in most cases, on the 1st day, followed by expulsion on the 3rd day in 2 cases, on the 4th day in 3 cases, on the 5th day in 3 cases, and on the 8th day in 1 case. 2 patients failed to abort. There were no complications, and only 1 patient required blood transfusion. Normal ovarian activity resumed in all cases. RU-486 can also be used to induce menstruation when administered in a dose of 50 mg a day for 4 days beginning on the 22nd day of a normal cycle. The use of RU-486 as an abortifacient agent seems to be more effective than the use of massive doses of estrogen or of prostaglandins, and to be certainly less traumatic than curettage or vacuum aspiration. Contraindications to its use and potential side effects, especially hepatic, have still to be established.^ieng

[The effects of an antiprogesterone steroid in women: interruption of the menstrual cycle and of early pregnancy]. / Effet d'un stéroide anti-progestérone chez la femme: interruption du cycle menstruel et de la grossesse au début.

RU-486 is a steroid which possesses a great affinity for the progesterone receptor, does not have a progesterone activity, but is indeed a strong antagonist of progesterone effects in animals. Oral administration induces the interruption of the luteal phase of the menstrual cycle and that of early pregnancy in women. Its mode of administration and its properties enable us to envisage a new methodology for menstrual cycle regulation and human birth control.

[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.