The effects of a once-a-week steroid contraceptive (R2323) on lipid and carbohydrate metabolism in women during three months of use.

Forty-four women were prospectively evaluated with a 3-hour oral glucose tolerance test while they used a new weekly oral contraceptive drug, R2323. The blood tests were carried out before the drug was administered and again 3 months after its use. Both blood glucose and plasma insulin levels were measured. In the 40 women with a "normal" control glucose tolerance test, it was found that only the 1-hour blood glucose value was significantly elevated after 3 months of drug use and the plasma insulin values were unchanged. The tests of three of the four women with borderline abnormal to abnormal control test curves converted to normal with 3 months of treatment and that of one remained unchanged. The fasting plasma cholesterol and triglyceride levels were unchanged over the 3 months' time. These results suggest that this steroid contraceptive has no effect on lipid metabolism. It also has minimal adverse effects on normal carbohydrate metabolism and may possibly improve abnormal metabolism.

[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.

The effect of progestin R 2323 released from vaginal rings on ovarian function.

PIP: The effect of progestin R 2323 released from intravaginal rings (IVR) on ovarian function was studied in 20 young healthy volunteers. The silastic IVRs containing 10, 20, 50, or 200 mg of progestin R 2323 were inserted on the 1st day after menstrual bleeding and removed 21 days after insertion. The IVRs were tolerated well without irritation or alteration of the vaginal mucosa. Control plasma estradiol and progesterone levels revealed 18 of 20 cycles were ovulatory. No ovulation was observed during treatment, as revealed by consistently suppressed progesterone levels. Normal ovulation resumed after removal of the rings. 3 women experienced withdrawal bleeding; 9 had breakthrough bleeding and 13 had a normal postovulatory bleeding 15-33 days after ring removal. It was concluded that the bleeding control was unsatisfactory with every dosage of R 2323 used in this study.^ieng

Contraceptive effectiveness of Silastic implants containing the progestin R-2323.

PIP: The long-term contraceptive effectiveness of subdermal silastic implants containing 30-40 mg of the progestin R-2323 (13-ethyl-17 alpha ethinyl-17 hydroxy-gona-4, 9,11-trien-3-one), was studied in 531 women. 98 women received 2 capsules (Group A), 180 received 3 capsules (Group B), 181 received 4 capsules (Group C) and 68 received 5 capsules (Group D). There were 5 pregnancies reported for Group A over 610 months of use, 3 pregnancies for 2124 months of use in Group B, 4 pregnancies for 2128 months of use in Group C, and Group D had 3 pregnancies over 732 months of use. All of the pregnancies in Group A occurred in the first 4 months while pregnancies in the other 3 groups generally occurred between Months 6-12 of use. Amenorrhea was most frequent during Months 2-6. The frequency of spotting and breakthrough bleeding was minimal.^ieng

[Hormone regulation of male fertility]. / Regulación hormonal de la fertilidad masculina

PIP: An innocuous, sure, reversible means of male fertility control which does not disturb the libido is being sought. 20 healthy volunteers from ages 20 to 36 participated, using a 2nd form of protection when necessary. 10 received implants of 60 mg testosterone equally divided into 3 tubes, and began oral ingestion of 100 mg weekly, divided into daily doses, of R2323 (13-ethyl-17-hydroxy-gonen 4,9,11, trien-3-one) until the sperm became ineffective. Then oral doses were given according to personal requirements from 50 to 25 mg. The 2nd series of 10 received no testosterone implants, but followed the same scheme for oral ingestion. All patients but 1 reduced their sperm count and 80% were low enough to consider the sperm inactive. For those who used the hormone treatment as the only protection against pregnancy, no pregnancy occurred. Of the 1st group, 2 had excessive weight gain, 3 felt their libido reduced, and 1 had pain in the nipples and 1 had pain in the hepatic region. Recuperation of normal sperm characteristics was slow, especially motility and vitality. The spermogram is so altered during treatment that any accidental pregnancy could result in a defective egg and serious complications. It should definitely be avoided.^ieng