title: Testicular growth and spermatogenesis: new goals for pubertal hormone replacement in boys with hypogonadotropic hypogonadism? -a multicentre prospective study of hCG/rFSH treatment outcomes during adolescence.
abstract: OBJECTIVE
  Testosterone treatment for pubertal induction in boys with hypogonadotropic hypogonadism (HH) provides virilization, but does not induce testicular growth or fertility. Larger studies evaluating the outcomes of gonadotropin replacement during adolescence have not been reported to date; whether previous testosterone substitution affects testicular responses is unresolved. We aimed to assess the effects of human chorionic gonadotropin (hCG) and recombinant FSH (rFSH) in boys and adolescents with HH with respect to a) testicular growth, b) spermatogenesis, c) quality of life (QoL) and to identify factors influencing therapeutic success.
  
  
  METHODS
  A prospective case study was conducted in 26 paediatric endocrine centres PATIENTS/INTERVENTIONS: HCG and rFSH were administered until cessation of testicular growth and plateauing of spermatogenesis to (1) prepubertal HH boys with absent or early arrested puberty (group A) and to (2) HH adolescents who had previously received full testosterone replacement (group B).
  
  
  METHODS
  Bi-testicular volumes (BTVs), sperm concentrations and QoL.
  
  
  RESULTS
  Sixty (34 A/26 B) HH patients aged 14-22 years were enrolled. BTVs rose from 5 ± 5 to 34 ± 3 ml in group A vs 5 ± 3 to 32 ± 3 ml in group B, with normal final BTVs (≥24 ml) attained in 74%/70% after 25/23 months in A/B, respectively. Sperm in the ejaculate were found in 21/23(91%)/18/19(95%), with plateauing concentrations after 31/30 months of hCG and 25/25 months of combined treatment in A/B. Sperm concentrations were normal (≥15 mill/ml) in 61%/32%, with mean concentrations of 40 ± 73 vs 19 ± 38 mill/ml in A/B (n.s.). Outcomes were better in patients without bilateral cryptorchidism, with non-congenital HH causes, higher baseline BTVs, and higher baseline inhibin B and AMH levels. QoL increased in both groups.
  
  
  CONCLUSIONS
  HCG/rFSH replacement during adolescence successfully induces testicular growth and spermatogenesis, irrespective of previous testosterone replacement, and enhances QoL.
authors.affiliation: Center of Reproductive Medicine and Andrology, Clinical Andrology, University of Münster, Muenster, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Rohayem
authors.affiliation: Children's Hospital Essen, Department of Paediatric Endocrinology and Diabetes, University Duisburg-Essen, Essen, Germany.
authors.forename: Berthold P
authors.initials: BP
authors.lastname: Hauffa
authors.affiliation: The Royal Children's Hospital, Melbourne, Vic., Australia.
authors.forename: Margaret
authors.initials: M
authors.lastname: Zacharin
authors.affiliation: Center of Reproductive Medicine and Andrology, Clinical Andrology, University of Münster, Muenster, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Kliesch
authors.affiliation: Center of Reproductive Medicine and Andrology, Clinical Andrology, University of Münster, Muenster, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Zitzmann
mesh_terms: D000293:Adolescent; D054304:Anti-Mullerian Hormone / Q000097:blood; D015415:Biomarkers / Q000097:blood; D006063:Chorionic Gonadotropin / Q000494:pharmacology / Q000627:therapeutic use*; D005640:Follicle Stimulating Hormone / Q000494:pharmacology / Q000627:therapeutic use*; D020249:Hormone Replacement Therapy; D006801:Humans; D007006:Hypogonadism / Q000188:drug therapy*; D007265:Inhibins / Q000097:blood; D008297:Male; D011446:Prospective Studies; D011627:Puberty / Q000187:drug effects; D011788:Quality of Life; D013091:Spermatogenesis / Q000187:drug effects*; D013737:Testis / Q000187:drug effects* / Q000254:growth & development; D013739:Testosterone / Q000494:pharmacology / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D015415:Biomarkers; D006063:Chorionic Gonadotropin; C422364:inhibin B; D013739:Testosterone; D007265:Inhibins; D054304:Anti-Mullerian Hormone; D005640:Follicle Stimulating Hormone