Abstract

Twenty-one-day treatment cycles of ethynylestradiol or mestranol at dosages of 50 to 100 mug per day were administered to 191 normal volunteer women from six cycles, followed by six cycles of this estrogen treatment combined with 2.5 mg. of norethindrone acetate, 2 mg. of megestrol acetate, or 0.5 mg. of norgestrel. The drugs were prepared to insure uniform bioavailabiltiy. Plasma FSH and LH were determined by radioimmunoasay during the last week of medication intake in each cycle. In another study, a large number of blood samples were obtained at various times during the menstrual cycle from women using IUD's (as a control population) and from women who had been taking oral contraceptives regularly for 5 to 12 years. With the various estrogen treatments, the median FSH level showed no change at any estrogen dose at the end of the first cycle. From the second cycle on, a stable, dose-related fall was obtained with the 80 or 100 mug per day doses. The addition of any of the three progestins caused a prompt, stable, further fall in FSH level. By contrast, the median LH level rose in the first cycle with all estrogen regimens, and then fell progressively in a dose-related fashion in cycles 2 to 6. The addition of a progestational agent also caused a further prompt and stable fall in LH during cycles 7 to 12. Except for a minimal indication of greater LH suppression by ethynylestradiol as compared to mestranol at 50 mug per day, all other indices and dosages showed ethynylestradiol and mestranol to be essentially equipoten under these experimental conditions. Long-term administration of oral contraceptives produced a comparable degree of gonadotropin suppression. There was a suggestion of slightly less FSH suppression with agents using 50 to 75 mug per day of estrogen than from those with 100 mug per day. Both in normal controls (IUD cycles) and in cycles under chronic treatment with oral contraceptives, pulses of both FSH and LH were seen with some frequency, at times distant from the "periovulatory" period. The significance and origin of these random FSH and LH pulses is unknown.

PIP:

The effects of ethinyl estradiol (EE) or mestranol on plasma follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were studies in 191 normal women. The women received 50-100 mcg/day of the estrogens over 21-day cycles for 6 cycles, followed by the addition of 2.5 mg norethindrone acetate, 2 mg megestrol acetate, or .5 mg norgestrel to the estrogens for 6 more cycles. Women using an IUD (controls) and women who had been taking oral contraceptives regularly for 5-12 years were also studied. At the end of the 1st cycle, median FSH levels did not change with any dose of EE or mestranol. However, from the 2nd cycle on, a dose-related FSH decrease was observed with 80 or 100 mcg doses of the estrogens. The addition of any of the 3 progestins promptly resulted in a further, although steady, decline in FSH levels. An increase in LH levels was observed in the 1st cycle of treatment with estrogens, although levels progressively declined, according to dose, during Cycles 2-6. Initiation of the combined treatment caused a further decrease in LH during Cycles 7-12. EE and mestranol were similarily equipotent, although EE was slightly more effective in suppressing LH at the 50 mcg dose. A comparable degree of LH and FSH suppression was found in the oral contraceptive group, although formulations containing 50-75 mcg/day estrogen were not quite as effective in suppressing FSH as were formulations containing 100 mcg estrogen. Sporadic increases in LH and FSH were observed with some frequency in the IUD cycles and in cycles involving therapeutic doses of oral contraceptives. The origin and meaning of these randon pulses is unknown.