The mechanism of action of a new low-dosed combined oral contraceptive

Abstract

The effect of a new low-dosed combined oral contraceptive (OC) containing 37.5 microgram ethinyl estradiol and 0.75 mg lynestrenol (Ovoresta M) upon gonadotropin release and follicular activity was studied in two groups of normally cyclic women. When the administration of the OC was started on day 1 of the cycle, the normal pattern of gonadotropin secretion was disrupted, and the midcycle LH and FSH peak was abolished. The mean level of LH and FSH was somewhat lower than in normal cycles, but the difference was not significant. In one case, serum estradiol rose to the level of the normal cycle indicating follicular activity. Even though there was a rise in serum estradiol to normal values when the OC was started on day 10 of the cycle (in 4/5), both the midcycle LH and FSH surge and ovulation were suppressed (in 3/4). The pituitary response to 100 microgram LH-RH on day 21 was impaired. The LH-response correlated significantly with the serum estradiol concentration. In summary, the low-dosed OC exerts its effect by interfering with follicular ripening and inhibiting the preovulatory LH surge.

PIP: A new low-dose combined oral contraceptive (OC) which was formulated with 37.5 mcg of ethinylestradiol and .75 mg of lynestrenol (Ovoresta M) was studied to determine its mechanism of action. 23 female volunteers, aged 21-34 years, were studied. 6 women took the OC beginning on Day 1 of cycle (Group 1), 5 women started the OC on Day 10 (Group 2), and 12 were controls. On Day 21, a luteinizing hormone-releasing hormone stimulation test was performed. In Group 1, the results of gonadotropin and hormonal tests were disruptive, showing that the normal pattern of gonadotropin secretion was altered, and the midcycle luteinizing hormone and follicle stimulating hormone peaks were abolished. In addition, mean levels of luteinizing hormone and follicle stimulating hormone were somewhat lower than in normal cycles, but not significantly so. 1 case in Group 1 showed estradiol levels indicative of the normal cycle and follicular activity. Group 2 subjects (started OC on Day 10) also showed both the midcycle luteinizing hormone and follicle stimulating hormone surge and suppressed ovulation (3 of 4) even though there was a rise in serum estradiol to normal values in this group (4 of 5). In addition, the pituitary response to gonadotropin-releasing hormone stimulation was impaired, and the luteinizing hormone response correlated significantly with the serum estradiol concentration. Hence, ovulation is suppressed by this low-dose OC through interference with follicular ripening and inhibition of the preovulatory luteinizing hormone surge.