Late luteal administration of the antiprogesterone RU486 in normal women: effects on the menstrual cycle events and fertility control in a long-term study.

Twelve regularly cycling women, with contraindications to other methods of contraception, received RU486 (Roussel UCLAF, Romainville, France), once a month as a method of fertility control. The study was designed for 18 consecutive cycles. Each patient recorded basal body temperature, detected urinary luteinizing hormone peak, and collected saliva samples during each luteal phase for progesterone (P) determinations. A single dose of RU486, 600 mg, was given on the day before the expected date of the menses and 8 days later in case of continuing pregnancy after the first dose. Blood samples were collected for estradiol, P, and beta-human chorionic gonadotropin analyses on these two occasions. The compliance was poor and the results of only 137 cycles were obtained. The menstrual cyclicity was not significantly modified during this long-term study. Of the 137 cycles, 22 pregnancies occurred (16%), and 4 (18.2%) were not interrupted by the second dose of RU486. Thus, because of the high failure rate, use of RU486 at the time of the natural P withdrawal cannot be advocated as a "once-a-month" contragestive agent.

[Contraception at risk]. / La contraception à risque.

PIP: Certain physiological and pathological conditions in women require choice of a contraceptive method that will not aggravate the condition or exacerbate known side effects. IUDs and oral contraceptives (OCs) are not appropriate for the immediate postpartum. Low dose progestins appear best suited and can be started on the 5th day after delivery. IUDs and high dose discontinuous progestins are the best choices for the menopausal period, but contraindications to them must be respected. Contraception with a dominant progestational climate is required in case of benign breast disease. Low dose progestins may cause luteal insufficiency and low dose combined OCs may allow endogenous estradiol secretion poorly balanced by the progestin. All progestin-dominant formulations and discontinuous 19-norsteroids may be used. 19-norsteroids appear suitable for women with breast cancer because of their antiestrogenic activity. High dose progestins are advisable for women with precancerous or cancerous endometrial pathology. Estrogens should be avoided in such cases. Cervical cancer has never been proven to be hormonodependent, and at present the use of hormonal contraception in cervical dysplasia is not contraindicated except after pelvic radiation for invasive cancer. Use of the IUD has the same indications as for the general population after lesions have been treated. In cases of hyperlipidemia, low doses of continuously administered 19-norsteroids cause a decline of high density lipoprotein (HDL) cholesterol but are considered to be without longterm metabolic effects. The new progestin desogestrel does not diminish HDL cholesterol. Many cases of hyperlipidemia and hypercholesterolemia contraindicate OCs at the usual dose and require mechanical contraception, although low dose progestins may be considered. Derivatives of 17-hydroxyprogesterone are without effects on lipid metabolism but are less reliable. No contraceptive method is fully satisfactory for diabetics. Hormonal contraception is risky because of possible metabolic and vascular effects. Low dose progestins have the fewest side effects but are often poorly tolerated. IUDs are often used for diabetics despite possible increased risks of infection and failure. Hypertensive women should not use combined OCs or high-dose 19-norsteroids, but low dose progestins carry no risk of hypertension. Women at vascular risk are advised to use IUDs if no specific contraindications are found. Otherwise low-dose progestins are an acceptable choice. Low dose progestins are often the only possibility for cardiac patients. Nonhypertensive women with renal insufficiency can use OCs under careful supervision if there are no contraindications. Combined OCs are contraindicated when there is any disturbance of hepatic function, but low dose progestins or mechanical means are acceptable. Chronic use of certain drugs which act as enzymatic inductors is incompatible with hormonal contraception.^ieng

Termination of early pregnancy by the progesterone antagonist RU 486 (Mifepristone).

We studied the effects of the progesterone antagonist RU 486 in 100 women with early, unwanted pregnancy (within 10 days of the expected onset of the missed menstrual period). Thirty-four women received oral doses of 400 mg (in four days), 26 received 600 mg (in four days), and 40 received 800 mg (in two days). Uterine bleeding occurred in all patients within four days of the first dose and continued for 5 to 17 days. In 85 of the women, a dramatic decrease in the plasma chorionic gonadotropin level was observed on day 6, and an empty uterus was confirmed by ultrasonography on day 13. Hence, these women were considered to have had a complete abortion. Fifteen subjects had persistently elevated plasma chorionic gonadotropin levels on day 6 and were considered not to have responded to RU 486. They all had uterine evacuation, which was facilitated by a softening of the cervix. The percentage of women with complete abortion was similar in all dosage groups. Furthermore, plasma levels of immunoreactive RU 486 were similar in subjects with and without complete abortion. The only important side effect observed in the responders was prolonged uterine bleeding in 18 percent, but neither blood transfusion nor curettage was required. We conclude that RU 486 is an effective and safe method for termination of very early pregnancy but that it should be used only under close medical supervision.

Comparative effects of cyproterone acetate or a long-acting gonadotropin-releasing hormone agonist in polycystic ovarian disease.

A randomized cross-over study was done to compare the therapeutic efficacy of cyproterone acetate (CPA) and a depot preparation of the LHRH superagonist (DTrp6-LHRH) in 10 patients with polycystic ovarian disease (PCO). All patients were treated with both agents (50 mg/day CPA, orally and (3 mg DTrp6-LHRH, im, approximately once a month) for 3 months, the 2 treatment periods being separated by 6 months. Both treatments resulted in marked clinical improvement, with diminished acne and seborrhoea and normalization of ovarian size by ultrasonographic criteria. In response to CPA treatment, basal plasma gonadotropin levels decreased, but the response to a LHRH test was not completely suppressed. Plasma estradiol, estrone, testosterone, and androstenedione levels significantly decreased, but urinary 3 alpha-androstanediol and plasma dehydroepiandrosterone sulfate levels did not change significantly. In contrast to CPA treatment, both basal and stimulated gonadotropin levels were completely suppressed after 3 weeks of treatment with DTrp6-LHRH. After a slight initial evaluation on day 2, plasma estrogen and androgen levels, with the exception of dehydroepiandrosterone sulfate fell into the castrate range urinary 3 alpha-androstanediol excretion decreased significantly. Thus, in patients with PCO, LHRH-A induced more complete gonadotropin inhibition than did CPA. After cessation of either therapy, the disease rapidly recurred.