THE MECHANISM IN INHIBITION OF OVULATION IN ORAL CONTRACEPTION. II.

Abstract

ABSTRACT 22 normally menstruating women were treated cyclically with a daily dose of 5 mg of 6-methyl-6-dehydro-17α-acetoxyprogesterone (megestrol acetate) + 0.1 mg of 17α-ethynyl-oestradiol-3-methylether (mestranol) for a period of 1 to 20 cycles. It has previously been shown by laparotomy, that this dose is effective for the inhibition of ovulation. Studies on the excretion of total gonadotrophins led to the assumption that the mechanism of this inhibition of ovulation involved a central effect on the hypothalamo-pituitary system. We therefore tried to counteract this effect and induce ovulation during the last treatment-cycle by (1) the administration of pregnant mares' serum gonadotrophin (PMS) alone, (2) human chorionic gonadotrophin (HCG) alone or (3) a combination of both. The standard dose was: 1500 IU of PMS on days 8, 10 and 12 and 4500 IU of HCG on days 13, 14 and 15. The response of the ovaries was assessed at laparotomy on day 24 by direct inspection and by histological examination of biopsies of the ovaries and the endometrium. Stimulation with PMS only did not induce ovulation, not even during the first month. With HCG alone it was – with one exception – only possible to induce ovulation in the first two months, but with PMS + HCG we found that ovulation occurred even after 20 months of treatment. It was concluded that the mechanism of inhibition of ovulation is essentially an inhibition of the pituitary gonadotrophins. It is probable that the luteinizing hormone (LH) is inhibited before the follicle stimulating hormone (FSH), but prolonged treatment, causes an inhibition of both LH and FSH.