Treatment of gonadotropin-deficient boys with recombinant human FSH: long-term observation and outcome.
BACKGROUND
Boys with prepubertal onset of hypogonadotropic hypogonadism (HH) are at a risk of poor testis growth and impaired spermatogenesis. One potential cause for this is deficient proliferation of immature Sertoli cells before and during puberty due to the absence of FSH.


OBJECTIVE
To evaluate the effects of recombinant human FSH (r-hFSH) and human chorionicgonadotropin (hCG) on testicular function and pubertal development in boys with prepubertal onset of HH.


METHODS
Retrospective clinical study.


METHODS
Two university central hospitals, pediatric referral endocrinology outpatient clinics.


METHODS
Fourteen boys (aged, 9.9-17.7 years) with prepubertal (testicular volume (TV) <3 ml) onset of HH (idiopathic HH, n=2; Kallman syndrome, n=2; idiopathic panhypopituitarism, n=4; organic panhypopituitarism, n=6).


METHODS
Treatment with r-hFSH alone (2 mo-2.8 years) prior to induction of puberty with the combination of FSH and hCG.


METHODS
Progression of puberty, change in serum inhibin B, spermatogenesis.


RESULTS
r-hFSH alone increased testicular volume twofold, from 0.9+/-0.6 ml (mean+/-s.d.) to 1.8 +/- 1.1 ml (P<0.005), and serum inhibin B threefold, from 27+/-14 to 80+/-57 pg/ml (P<0.01). Three boys with an apparent absence of postnatal hypothalamic-pituitary-testicular axis activation displayed attenuated inhibin B responses to long-term (>or=1 year) r-hFSH (P<0.01). Further significant increase in both TVand inhibin B occurred with induction of puberty with FSH and hCG (P<0.001). Seven boys provided semen samples: one had azoospermia, and others displayed a maximal sperm count range from 2.9 to 92 million/ml (median 8.5 million/ml).


CONCLUSIONS
(i) r-hFSH induces prepubertal testis growth and increases circulating inhibin B levels, findings suggesting proliferation of immature Sertoli cells. (ii) Puberty was successfully induced with hCG and r-hFSH following r-hFSH priming. (iii) Inhibin B appears useful for monitoring spermatogenetic activity in boys treated with hCG. (iv) Despite the extremely small initial testis volume, six out of seven patients (86%) primed with r-hFSH displayed sperm in the ejaculate suggesting beneficial effect of r-hFSH priming on testicular function later in life.
Raivio
Taneli
T
Hospital for Children and Adolescents, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland. traivio@gmail.com
Wikström
Anne M
AM
Dunkel
Leo
L
D000293:Adolescent; D002648:Child; D006063:Chorionic Gonadotropin / Q000627:therapeutic use; D005640:Follicle Stimulating Hormone / Q000627:therapeutic use*; D006062:Gonadotropins / Q000172:deficiency*; D020249:Hormone Replacement Therapy; D006801:Humans; D007006:Hypogonadism / Q000188:drug therapy*; D007265:Inhibins / Q000097:blood; D008134:Long-Term Care; D008137:Longitudinal Studies; D008297:Male; D011627:Puberty / Q000502:physiology; D011994:Recombinant Proteins / Q000627:therapeutic use; D012189:Retrospective Studies; D013091:Spermatogenesis / Q000187:drug effects; D013737:Testis / Q000033:anatomy & histology; D016896:Treatment Outcome
D006063:Chorionic Gonadotropin; D006062:Gonadotropins; D011994:Recombinant Proteins; C422364:inhibin B; D007265:Inhibins; D005640:Follicle Stimulating Hormone