According to the 2-cell theory, ovarian steroidogenesis requires the coordinate action of both FSH and LH. To evaluate the relative importance of these hormones in follicular maturation, a randomized cross-over study was performed in 10 women with complete gonadotropin deficiency (absence of pulsatile LH secretion and no LH response to LHRH). Five women were treated with highly purified FSH (LH bioactivity, 0.09%) and 3 months later with human menopausal gonadotropin (hMG; LH bioactivity, 65%), each given for 10 days at a daily dose of 225 IU FSH, im. The sequence was reversed in the other 5 women. hCG (5000 IU) was administered im 24 h after the last injection of FSH or hMG. Plasma estradiol (E2), estrone (E1), androstenedione (A), testosterone, LH, and FSH concentrations and urinary LH and FSH were measured daily by RIA. Ultrasonography was performed during each treatment and 2 days after each hCG injection. After FSH treatment, mean plasma and urinary FSH levels increased, mean plasma LH did not change, and urinary LH increased slightly but not significantly from 91 +/- 32 (SE) to 164 +/- 55 mIU/24 h (10(-3) IU/24 h). After hMG treatment, mean plasma and urinary LH and FSH levels increased accordingly. The mean basal plasma E2 [11 +/- 1 pg/mL (40 +/- 4 pmol/L)] and E1 [14 +/- 4 pg/mL (52 +/- 15 pmol/L)] levels increased after FSH treatment to 207 +/- 69 pg/mL (760 +/- 253 pmol/L) and 82 +/- 21 pg/mL (303 +/- 78 pmol/L), respectively (P less than 0.01), but plasma A did not change. In response to hMG, the mean plasma E2, E1, A, and testosterone levels increased more than during FSH treatment. Ultrasonography revealed multiple preovulatory follicles (greater than or equal to 16 mm) in 2 women after hMG and 1 woman after FSH treatment; therefore, hCG was not administered. In 3 women given FSH, hCG did not induce ovulation. hCG induced ovulation in 8 women given hMG and in 6 women given FSH, based on ultrasonography and plasma progesterone levels. Thus, in the presence of profound gonadotropin deficiency pharmacological doses of FSH, with minute LH contamination, are capable of stimulating ovarian follicular maturation, underlining the key role of FSH in folliculogenesis.

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.