title: Congenital combined pituitary hormone deficiency patients have better responses to gonadotrophin-induced spermatogenesis than idiopathic hypogonadotropic hypogonadism patients.
abstract: OBJECTIVE
  Do patients with congenital combined pituitary hormone deficiency (CCPHD) have different responses to gonadotrophin-induced spermatogenesis compared with those with idiopathic hypogonadotropic hypogonadism (IHH)?
  
  
  CONCLUSIONS
  CCPHD patients have a better response to gonadotrophin therapy than IHH patients.
  
  
  BACKGROUND
  Gonadotrophins are effective in inducing spermatogenesis in patients with hypogonadotropic hypogonadism.
  This retrospective cohort study included 75 patients, 53 of whom had IHH and 22 CCPHD. They were diagnosed, treated and followed up between January 2008 and December 2013.
  
  
  METHODS
  Combined gonadotrophin therapy, consisting of human chorionic gonadotrophin and human menopausal gonadotrophin, was administered for 24 months. The success rate of spermatogenesis (≥1 sperm in ejaculate), serum total testosterone level, testicle size and sperm concentration during the treatment, as well as the first time sperm were detected in the ejaculate, were compared between the two diagnostic groups. All patients were treated in Peking Union Medical College Hospital.
  
  
  RESULTS
  Spermatogenesis was successfully induced in 85% of IHH patients and 100% of CCPHD patients after 24-month combined gonadotrophin treatment (P = 0.03). In comparison with IHH, CCPHD patients had larger mean testicle sizes during the gonadotrophin treatment at 6, 12, 18 and 24 months (all P < 0.05). The initial time for sperm appearance in IHH group (n = 45) and CCPHD group (n = 22) was 13.2 ± 5.9 versus 10.4 ± 3.8 months (P = 0.045). Generally, CCPHD patients had higher sperm counts [median (quartiles)] than IHH patients during the treatment, but the difference was only statistically significant at 12 months of treatment, 3.3 (1.8, 12.0) versus 1.0 (0.0, 4.6) million/ml, P = 0.001. There was a higher level of serum total testosterone [mean (SD)] in the CCPHD group than the IHH group (676 ± 245 versus 555 ± 209 ng/dl, P = 0.035).
  
  
  CONCLUSIONS
  First, the inherent nature of a retrospective designed study was a main shortcoming. Secondly, pathological gene mutations in IHH and CCPHD patients should be further investigated. Clarification of the underlying mechanisms between cryptorchidism and mutated genes may provide more information for the divergent therapeutic responses between two groups. Only a minority of patients were actively seeking to have children so information about fertility is limited.
  
  
  CONCLUSIONS
  CCPHD patients had a lower incidence of cryptorchidism and a better response to gonadotrophin therapy than IHH patients, reflecting multiple defects on the different levels of reproduction axis in IHH. Furthermore, growth hormone is not indispensable for spermatogenesis in CCPHD patients.
  
  
  BACKGROUND
  The study was supported by Natural Science Foundation of China (No: 81100416). None of the authors has any conflicts of interest to declare.
authors.affiliation: Key Laboratory of Endocrinology, Ministry of Health, Department of Endocrinology, Peking Union Medical College Hospital, Beijing 100730, China.
authors.forename: Jiangfeng
authors.initials: J
authors.lastname: Mao
authors.affiliation: Key Laboratory of Endocrinology, Ministry of Health, Department of Endocrinology, Peking Union Medical College Hospital, Beijing 100730, China.
authors.forename: Hongli
authors.initials: H
authors.lastname: Xu
authors.affiliation: Key Laboratory of Endocrinology, Ministry of Health, Department of Endocrinology, Peking Union Medical College Hospital, Beijing 100730, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Wang
authors.affiliation: Key Laboratory of Endocrinology, Ministry of Health, Department of Endocrinology, Peking Union Medical College Hospital, Beijing 100730, China.
authors.forename: Bingkun
authors.initials: B
authors.lastname: Huang
authors.affiliation: Key Laboratory of Endocrinology, Ministry of Health, Department of Endocrinology, Peking Union Medical College Hospital, Beijing 100730, China.
authors.forename: Zhaoxiang
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Key Laboratory of Endocrinology, Ministry of Health, Department of Endocrinology, Peking Union Medical College Hospital, Beijing 100730, China.
authors.forename: Junjie
authors.initials: J
authors.lastname: Zhen
authors.affiliation: Key Laboratory of Endocrinology, Ministry of Health, Department of Endocrinology, Peking Union Medical College Hospital, Beijing 100730, China.
authors.forename: Min
authors.initials: M
authors.lastname: Nie
authors.affiliation: Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Le
authors.initials: L
authors.lastname: Min
authors.affiliation: Key Laboratory of Endocrinology, Ministry of Health, Department of Endocrinology, Peking Union Medical College Hospital, Beijing 100730, China wsheyan@vip.sina.com.
authors.forename: Xueyan
authors.initials: X
authors.lastname: Wu
mesh_terms: D000293:Adolescent; D000328:Adult; D002452:Cell Count; D006063:Chorionic Gonadotropin / Q000008:administration & dosage / Q000494:pharmacology*; D003456:Cryptorchidism / Q000209:etiology; D005500:Follow-Up Studies; D006801:Humans; D007006:Hypogonadism / Q000150:complications / Q000188:drug therapy*; D007018:Hypopituitarism / Q000150:complications / Q000151:congenital / Q000188:drug therapy*; D008297:Male; D008596:Menotropins / Q000008:administration & dosage / Q000494:pharmacology*; D017063:Outcome Assessment, Health Care; D012102:Reproductive Control Agents / Q000008:administration & dosage / Q000494:pharmacology*; D012189:Retrospective Studies; D013076:Sperm Count; D013091:Spermatogenesis / Q000187:drug effects*; D013737:Testis / Q000187:drug effects*; D013739:Testosterone / Q000097:blood*; D055815:Young Adult
chemical_list: D006063:Chorionic Gonadotropin; D012102:Reproductive Control Agents; D013739:Testosterone; D008596:Menotropins
keywords: congenital combined pituitary hormone deficiency; gonadotrophin-induced spermatogenesis; idiopathic hypogonadotropic hypogonadism