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

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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 μg ethinyl estradiol (EE) + 75 μg gestodene (GSD) (Harmonet®, Wyeth-Lederle; n = 15), 20 μg EE + 150 μg desogestrel (DSG) (Mercilon®, Organon n = 17), or 30 μg EE + 150 μg DSG (Marvelon®, 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 μg EE group compared with both 20 μg 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 μg 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 μg EE group compared with both 20 μg EE study groups. Dominant follicles (defined as follicle diameter ≥10 mm) were observed at the end of the pill-free interval in both 20 μg EE groups (in 27% and 18% of women, respectively) but not in the 30 μg EE group. Finally, the area-under-the-curve for E 2 was statistically significantly lower in the 30 μg EE group compared with both 20 μg 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 μg EE study groups.