Activity of the pituitary-ovarian axis in the pill-free interval during use of low-dose combined oral contraceptives

This study was performed to evaluate pituitary-ovarian recovery in the pill-free interval during use of three low-dose combined oral contraceptives (COC). Either the estrogen component or the progestin component was comparable in the study groups, to evaluate their relative influence. Serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), and estradiol (E-2) levels were measured and follicle number and size estimated by transvaginal sonography daily during the 7-day pill-free interval in 44 healthy volunteers using three different low-dose oral contraceptives. Healthy volunteers were enrolled using 20 mu g ethinyl estradiol (EE) + 75 mu g gestodene (GSD) (Harmonet(R), Wyeth-Lederle; n = 15), 20 mu g EE + 250 mu g desogestrel (DSG) (Mercilon(R), Organon n = 17), or 30 mu g EE + 150 mu g DSG (Malvelon(R) Organon, n = 12) given according to the usual regimen of one tablet daily during 3 weeks and 1 week pill-free interval. No ovulations were observed. Pituitary hormones were not statistically significantly different at the beginning of the pill-free interval between the study groups. FSH concentrations were significantly higher at the end of the pill-free interval in the 30 mu g EE group compared with both 20 mu g EE groups (7.0 [0.6-12.4] IU/L vs 4.9 [1.4-6.1] IU/L and 4.5 [2.4-7.4] IU/L; p = 0.001). In both 20 mu g EE groups, a single persistent follicle (24 and 28 mm) was present in one subject. Follicle diameters were statistically significantly smaller at the beginning and at the end of the pill-free period in the 30 mu g EE group compared with both 20 mu g EE study groups. Dominant follicles (defined as follicle diameter greater than or equal to 10 mm) were observed at the end of the pill-free interval in both 20 mu g EE groups (in 27% and 18% of women, respectively) but not in the 30 mu g EE group. Finally, the area-under-the-curve for E-2 was statistically significantly lower in the 30 mu g EE group compared with both 20 mu g EE groups. In conclusion, the EE content rather than the progestin component in the studied COC determined the extent of residual ovarian activity at the beginning of the pill-free interval. Dominant follicles were encountered only in the 20 mu g EE study groups. CONTRACEPTION 1999;59:237-243 (C) 1999 Elsevier Science Inc. All rights reserved.