Serum hormone concentrations during treatment with multiple rising doses of recombinant follicle stimulating hormone (Puregon) in men with hypogonadotropic hypogonadism.
OBJECTIVE
To study increases of serum FSH and gonadal response in gonadotropin-deficient men treated with recombinant FSH (Puregon; NV Organon, Oss, The Netherlands).


METHODS
An open, prospective, multiple rising dose study in which volunteers received single daily IM doses of recombinant FSH for 3 weeks. The dose administered was increased at weekly intervals: the first 7 days, 75 IU/d; the subsequent 7 days, 150 IU/d; and the last 7 days, 225 IU/d.


METHODS
Nine men suffering from isolated gonadotropin deficiency or panhypopituitarism.


METHODS
Immunoreactive FSH, LH, inhibin, T, and androstenedione.


RESULTS
Serum immunoreactive FSH (median) rose in accordance with the recombinant FSH doses administered from 0.5 mIU/mL (range < 0.05 to 1.9 mIU/mL) at baseline to 4.3 mIU/mL (range 2.0 to 8.5 mIU/mL), 8.4 mIU/mL (range 4.9 to 17.8 mIU/mL), and 13.6 mIU/mL (5.6 to 28.4 mIU/mL) after 1, 2, and 3 weeks of medication, respectively. The elimination half-life of recombinant FSH was 48 +/- 5 hours (mean +/- SD), which was slightly longer than that reported after single dose administration of recombinant FSH (32 +/- 12 hours). The bioactivity of recombinant FSH was reflected by serum inhibin levels, which rose from 116 U/L (range 34 to 356 U/L) at baseline to 350 U/L (range 63 to 1,109 U/L) at day 22. However, serum FSH and inhibin levels did not correlate when compared after 1, 2, and 3 weeks of recombinant FSH administration. Serum immunoreactive LH, T, androstenedione, and E2 were 0.2 mIU/mL (range < 0.05 to 0.7 mIU/mL [conversion factor to SI unit, 1.0]), 58 ng/dL (range < 12 to 222 ng/dL [conversion factor to SI unit, 0.0347]), 14 ng/dL (range 6 to 115 ng/dL [conversion factor to SI unit, 0.0349]), and 14 pg/mL (range < 14 to 16 pg/mL [conversion factor to SI unit, 3.67]), respectively, at baseline and remained unchanged during the entire treatment period.


CONCLUSIONS
These data indicate that recombinant FSH treatment increases serum FSH in a dose-proportional fashion, increases inhibin secretion, and lacks intrinsic LH activity.
Mannaerts
B
B
Medical Research and Development Unit, NV Organon, Oss, The Netherlands.
Fauser
B
B
Lahlou
N
N
Harlin
J
J
Shoham
Z
Z
Bennink
H C
HC
Bouchard
P
P
D000328:Adult; D004334:Drug Administration Schedule; D005640:Follicle Stimulating Hormone / Q000008:administration & dosage*; D012739:Gonadal Steroid Hormones / Q000097:blood*; D006062:Gonadotropins / Q000172:deficiency*; D006801:Humans; D007006:Hypogonadism / Q000097:blood* / Q000188:drug therapy / Q000209:etiology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000008:administration & dosage*
D012739:Gonadal Steroid Hormones; D006062:Gonadotropins; D011994:Recombinant Proteins; D005640:Follicle Stimulating Hormone