Induction of follicular growth using recombinant human follicle-stimulating hormone in two volunteer women with hypogonadotropic hypogonadism.
OBJECTIVE
To examine the safety, tolerance, pharmacokinetics, follicular growth, and steroidogenesis after the administration of recombinant human FSH (Org 32489; Organon International, Oss, The Netherlands) in women with isolated hypogonadotropic hypogonadism.


METHODS
An open phase I multiple rising dose study with recombinant FSH in two hypogonadotropic but otherwise healthy women. The drug was administered intramuscularly one time per day for a maximum of 21 days, i.e., 75 IU for the first 7 days, 150 IU for the next 7 days, and 225 IU during the last 7 days. Treatment was discontinued if serum E2 was > or = 1,100 pmol/L and/or one or more growing follicle > 14 mm in diameter was observed. After the last recombinant FSH injection, subjects were monitored for another 3 weeks.


METHODS
Specialist Reproductive Endocrinology and Infertility Unit.


METHODS
Two women with isolated hypogonadotropic hypogonadism who did not want to get pregnant anymore.


METHODS
Serum FSH, androstenedione (A), T, P, LH, follicular growth, and endometrial thickness. Safety parameters: blood pressure, heart rate, urinalysis, hematology, blood biochemistry, and antirecombinant FSH antibodies.


RESULTS
Treatment with recombinant FSH resulted in dose-related increases of serum FSH. Both women showed follicular growth (diameter, 17 mm), whereas serum A concentrations were very low, and serum E2 concentrations rose to only 76.7 and 139.5 pmol/L, respectively. No antirecombinant FSH antibody formation or changes of safety variables were noted.


CONCLUSIONS
This study in two women with hypogonadotropic hypogonadism is consistent with the two-cell theory that FSH alone can induce follicular growth. The low concentrations of A and E2 indicate the need for LH to induce appropriate steroidogenesis. It was also found that recombinant FSH is well absorbed, safe, and well tolerated after daily treatment for up to 21 days.
Shoham
Z
Z
Department of Obstetrics and Gynecology, Kaplan Hospital, Rehovot, Israel.
Mannaerts
B
B
Insler
V
V
Coelingh-Bennink
H
H
D000328:Adult; D004958:Estradiol / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D006065:Gonadotropins, Pituitary / Q000172:deficiency*; D006801:Humans; D007006:Hypogonadism / Q000188:drug therapy* / Q000503:physiopathology; D006080:Ovarian Follicle / Q000187:drug effects* / Q000502:physiology; D011994:Recombinant Proteins / Q000627:therapeutic use
D006065:Gonadotropins, Pituitary; D011994:Recombinant Proteins; D004958:Estradiol; D005640:Follicle Stimulating Hormone