Induction of spermatogenesis by recombinant follicle-stimulating hormone (puregon) in hypogonadotropic azoospermic men who failed to respond to human chorionic gonadotropin alone.
A multicenter, open-label, randomized efficacy and safety study was performed with combined human chorionic gonadotropin (hCG) and recombinant follicle-stimulating hormone (recFSH) (Puregon(R)) treatment to induce spermatogenesis in hypogonadotropic hypogonadal male patients. Patients were pretreated for 16 weeks with hCG to normalize testosterone levels. A total of 30 of 49 (61%) subjects had normalized testosterone levels but were still azoospermic after the hCG-alone phase. These patients were randomized into 2 treatment schemes with recFSH (2 x 225 IU recFSH per week [group A] or 3 x 150 IU recFSH per week [group B]), in combination with hCG for a period of 48 weeks. Total testosterone increased during the hCG-alone period from 1.08 and 1.22 ng/mL to 6.26 and 4.52 ng/mL for groups A and B, respectively. Combined gonadotropin treatment was effective in inducing spermatogenesis (sperm count >/=1 x 10(6)/mL) in 14 of 30 subjects (47%) and this was achieved after a median duration of treatment of approximately 5.5 months. Treatment time necessary for first sperm cells to appear in the ejaculate was related to the initial testicular volume. Subjects with a history of maldescended testes (11 of 30 subjects, 37%) showed a lower mean response to treatment as indicated by the relatively lower number of subjects reaching levels of at least 1 x 10(6) sperm cells per milliliter. Combined testicular volume increased during combined gonadotropin treatment from 11.4 to 24.0 mL. Although subjects with a history of maldescended testes had a lower starting testicular volume, subjects with and without a history of maldescended testes showed approximately the same relative increase in testicular volume. Total testosterone levels showed only a minor further increase during the combined gonadotropin treatment period. In conclusion, a weekly dose of 450 IU (3 x 150 IU or 2 x 225 IU) recFSH, in addition to hCG, was able to induce spermatogenesis in many hypogonadotropic azoospermic men who failed to respond to treatment with hCG alone.
Bouloux
Pierre-Marc G
PM
Department of Endocrinology, The Royal Free Hospital, London, United Kingdom.
Nieschlag
Eberhard
E
Burger
Henry G
HG
Skakkebaek
Niels E
NE
Wu
Frederick C W
FC
Handelsman
David J
DJ
Baker
Gordon H W
GH
Ochsenkuehn
Robert
R
Syska
Annemarie
A
McLachlan
Robert I
RI
Giwercman
Aleksander
A
Conway
Ann J
AJ
Turner
Leo
L
van Kuijk
Jacqueline H M
JH
Voortman
Gerrit
G
D000328:Adult; D006063:Chorionic Gonadotropin / Q000008:administration & dosage* / Q000009:adverse effects; D004359:Drug Therapy, Combination; D043373:Follicle Stimulating Hormone, Human / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007006:Hypogonadism / Q000188:drug therapy*; D008297:Male; D009845:Oligospermia / Q000188:drug therapy*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects; D013091:Spermatogenesis / Q000187:drug effects*; D013737:Testis / Q000033:anatomy & histology / Q000187:drug effects; D013739:Testosterone / Q000097:blood; D016896:Treatment Outcome
D006063:Chorionic Gonadotropin; D043373:Follicle Stimulating Hormone, Human; D011994:Recombinant Proteins; D013739:Testosterone