Recombinant Human Luteinizing Hormone (LH) to Support Recombinant Human Follicle-Stimulating Hormone (FSH)-Induced Follicular Development in LH- and FSH-Deficient Anovulatory Women: A Dose-Finding Study1

The efficacy of recombinant human LH (rhLH) for supporting human (rhFSH)-induced follicular development was investigated in hypogonadotropic hypogonadal women (WHO group I anovulation). Patients (n = 38) were randomized to receive rhLH (0, 25, 75, or 225 IU/day) in addition to a fixed dose of rhFSH (150 IU/day). rhLH was found 1) to promote dose-related increases in estradiol (E2) and androstenedione secretion by rhFSH-induced follicles, i.e. serum concentrations on the last day of FSH administration were 65 ± 4, 195 ± 94, 1392 ± 585, and 2441 ± 904 pmol/L for E2 and 3.6 ± 0.9, 5.1 ± 1.3, 6.4 ± 1.3, and 6.7 ± 1.3 nmol/L for androstenedione for patients treated with 0, 25, 75, and 225 IU rhLH, respectively; 2) to increase ovarian sensitivity to FSH, as demonstrated by the proportion of patients who developed follicles after the administration of a fixed dose of FSH, i.e. 1 of 8, 3 of 7, 7 of 9, and 8 of 10 in patients treated with 0, 25, 75, and 225 IU rhLH, respectively; and 3) to enhance the ability of these follicles to luteinize when exposed to hCG. A daily dose of 75 IU rhLH was effective in the majority of women in promoting optimal follicular development (defined as ≥1 follicle ≥17 mm; E2, ≥400 pmol/L; midluteal phase progesterone, ≥25 nmol/L) and maximal endometrial growth. A minority of patients may require up to 225 IU/day. rhLH, given sc at a dose up to 225 IU/day, was not immunogenic and was well tolerated.