INDUCTION OF FOLLICULAR-GROWTH USING RECOMBINANT HUMAN FOLLICLE-STIMULATING-HORMONE IN 2 VOLUNTEER WOMEN WITH HYPOGONADOTROPIC HYPOGONADISM

Objective: To examine the safety, tolerance, pharmacokinetics, follicu lar growth, and steroidogenesis after the administration of recombinan t human FSH (Org 32489; Organon International, Oss, the Netherlands) i n women with isolated hypogonadotropic hypogonadism. Design: An open p hase I multiple rising dose study with recombinant FSH in two hypogona dotropic but otherwise healthy women. The drug was administered intram uscularly one time per day for a maximum of 21 days, i.e., 75 TCT for the first 7 days, 150 IU for the next 7 days, and 225 IU during the la st 7 days. Treatment was discontinued if serum E-2 was less than or eq ual to 1,100 pmol/L and/or one or more growing follicle >14 mm in diam eter was observed. After the last recombinant FSH injection, subjects were monitored for another 3 weeks. Setting: Specialist Reproductive E ndocrinology and Infertility Unit. Volunteers: Two women with isolated hypogonadotropic hypogonadism who did not want to get pregnant anymor e. Main Outcome Measure(s): Serum FSH, androstendione (A), T, P, LH, f ollicular growth, and endometrial thickness. Safety parameters: blood pressure, heart rate, urinalysis, hematology, blood biochemistry, and antirecombinant FSH antibodies. Result(s): Treatment with recombinant FSH resulted in dose-related increases of serum FSH. Both women showed follicular growth (diameter, 17 mm), whereas serum A concentrations w ere very low, and serum E-2 concentrations rose to only 76.7 and 139.5 pmol/L, respectively. No antirecombinant FSH antibody formation or ch anges of safety variables were noted. Conclusion(s): This study in two women with hypogonadotropic hypogonadism is consistent with the two-c ell theory that FSH alone can induce follicular growth. The low concen trations of A and E-2 indicate the need for LH to induce appropriate s teroidogenesis. II was also found that recombinant FSH is well absorbe d, safe, and well tolerated after daily treatment for up to 21 days. ( C) 1993 by American Society for Reproductive Medicine.