Stimulation of Ovarian Follicular Maturation With Pure Follicle-Stimulating Hormone in Women with Gonadotropin Deficiency

Abstract

According to the 2-cell theory, ovarian steroidogenesis requires the coordinate action of both FSH and LH. To evaluate the relative importance of these hormones in follicular maturation, a randomized cross-over study was performed in 10 women with complete gonadotropin deficiency (absence of pulsatile LH secretion and no LH response to LHRH). Five women were treated with highly purified FSH (LH bioactivity, 0.09%) and 3 months later with human menopausal gonadotropin (hMG; LH bioactivity, 65%), each given for 10 days at a daily dose of 225 IU FSH, im. The sequence was reversed in the other 5 women. hCG (5000 IU) was administered im 24 h after the last injection of FSH or hMG. Plasma estradiol (E₂), estrone (E₁), androstenedione (A), testosterone, LH, and FSH concentrations and urinary LH and FSH were measured daily by RIA. Ultrasonography was performed during each treatment and 2 days after each hCG injection. After FSH treatment, mean plasma and urinary FSH levels increased, mean plasma LH did not change, and urinary LH increased slightly but not significantly from 91 ± 32 (SE) to 164 ± 55 mIU/24 h (10⁻³ IU/24 h). After hMG treatment, mean plasma and urinary LH and FSH levels increased accordingly. The mean basal plasma E2 [11 ± 1 pg/mL (40 ± 4 pmol/L)] and E₁ [14 ± 4 pg/mL (52 ± 15 pmol/L)] levels increased after FSH treatment to 207 ± 69 pg/mL (760 ± 253 pmol/L) and 82 ± 21 pg/mL (303 ± 78 pmol/L), respectively (P < 0.01), but plasma A did not change. In response to hMG, the mean plasma E₂, E₁, A, and testosterone levels increased more than during FSH treatment. Ultrasonography revealed multiple preovulatory follicles (≥16 mm) in 2 women after hMG and 1 woman after FSH treatment; therefore, hCG was not administered. In 3 women given FSH, hCG did not induce ovulation. hCG induced ovulation in 8 women given hMG and in 6 women given FSH, based on ultrasonography and plasma progesterone levels. Thus, in the presence of profound gonadotropin deficiency pharmacological doses of FSH, with minute LH contamination, are capable of stimulating ovarian follicular maturation, underlining the key role of FSH in folliculogenesis