title: Pulsatile GnRH Therapy May Restore Hypothalamus-Pituitary-Testis Axis Function in Patients With Congenital Combined Pituitary Hormone Deficiency: A Prospective, Self-Controlled Trial.
abstract: The effectiveness of pulsatile gonadotropin-releasing hormone (GnRH) therapy in patients with congenital combined pituitary hormone deficiency (CCPHD) has not been investigated because of the limited number of patients, as well as these patients' presumed pituitary hypoplasia, poor gonadotrophic cell reserve, and impaired gonadotrophic response to GnRH.
  
  
  
  To assess the pituitary response to pulsatile GnRH therapy in men with CCPHD.
  
  
  
  Prospective, self-controlled, 3-month clinical trial.
  
  
  
  University endocrine clinic.
  
  
  
  Men with hypogonadotropic hypogonadism caused by CCPHD.
  
  
  
  Pulsatile GnRH was administered subcutaneously for 3 months.
  
  
  
  Primary endpoints were total serum testosterone, testicular volume, and luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels. Secondary endpoints included occurrence of spermatogenesis.
  
  
  
  A total of 40 men with CCPHD completed the study. Of these, 60% (24 of 40) showed a good response to pulsatile GnRH treatment (response group). At 3 months, their LH and FSH levels increased to within the normal range and their testosterone levels increased to 8.67 ± 4.83 nmol/L. Of the patients in the response group, 33.3% (8 of 24) of them achieved spermatogenesis. The remaining 40% (16 of 40) of patients had a poor response to pulsatile GnRH treatment. Magnetic resonance imaging (MRI) did not reveal any correlation between pituitary response and pituitary height and/or integrity of the pituitary stalk.
  
  
  
  This study suggests that gonadotrophs in patients with CCPHD can exist and be functional-even with MRI evidence of pituitary hypoplasia or dysplasia. Pulsatile GnRH therapy restored pituitary-testis axis function in 60% of patients with CCPHD. These results may directly guide the clinical therapeutic choice.
authors.affiliation: Department of Endocrinology, Peking Union Medical College Hospital, Key Laboratory of Endocrinology, Ministry of Health, Beijing 100730, China.
authors.forename: Junjie
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Department of Endocrinology, Peking Union Medical College Hospital, Key Laboratory of Endocrinology, Ministry of Health, Beijing 100730, China.
authors.forename: Jiangfeng
authors.initials: J
authors.lastname: Mao
authors.affiliation: Department of Endocrinology, Peking Union Medical College Hospital, Key Laboratory of Endocrinology, Ministry of Health, Beijing 100730, China.
authors.forename: Hongli
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Endocrinology, Peking Union Medical College Hospital, Key Laboratory of Endocrinology, Ministry of Health, Beijing 100730, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Endocrinology, Peking Union Medical College Hospital, Key Laboratory of Endocrinology, Ministry of Health, Beijing 100730, China.
authors.forename: Bingkun
authors.initials: B
authors.lastname: Huang
authors.affiliation: Department of Endocrinology, Peking Union Medical College Hospital, Key Laboratory of Endocrinology, Ministry of Health, Beijing 100730, China.
authors.forename: Zhaoxiang
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Endocrinology, Peking Union Medical College Hospital, Key Laboratory of Endocrinology, Ministry of Health, Beijing 100730, China.
authors.forename: Mingxuan
authors.initials: M
authors.lastname: Cui
authors.affiliation: Department of Endocrinology, Peking Union Medical College Hospital, Key Laboratory of Endocrinology, Ministry of Health, Beijing 100730, China.
authors.forename: Shuyu
authors.initials: S
authors.lastname: Xiong
authors.affiliation: Department of Endocrinology, Peking Union Medical College Hospital, Key Laboratory of Endocrinology, Ministry of Health, Beijing 100730, China.
authors.forename: Wanlu
authors.initials: W
authors.lastname: Ma
authors.affiliation: Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115.
authors.forename: Le
authors.initials: L
authors.lastname: Min
authors.affiliation: Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115.
authors.forename: Ursula B
authors.initials: UB
authors.lastname: Kaiser
authors.affiliation: Department of Endocrinology, Peking Union Medical College Hospital, Key Laboratory of Endocrinology, Ministry of Health, Beijing 100730, China.
authors.forename: Min
authors.initials: M
authors.lastname: Nie
authors.affiliation: Department of Endocrinology, Peking Union Medical College Hospital, Key Laboratory of Endocrinology, Ministry of Health, Beijing 100730, China.
authors.forename: Xueyan
authors.initials: X
authors.lastname: Wu
mesh_terms: D000328:Adult; D004334:Drug Administration Schedule; D005640:Follicle Stimulating Hormone / Q000097:blood; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage* / Q000627:therapeutic use; D020249:Hormone Replacement Therapy / Q000379:methods*; D006801:Humans; D007018:Hypopituitarism / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D007031:Hypothalamus / Q000503:physiopathology; D055104:Infusions, Subcutaneous; D007986:Luteinizing Hormone / Q000097:blood; D008279:Magnetic Resonance Imaging; D008297:Male; D010902:Pituitary Gland / Q000000981:diagnostic imaging / Q000503:physiopathology; D011446:Prospective Studies; D013737:Testis / Q000473:pathology / Q000503:physiopathology; D013739:Testosterone / Q000097:blood; D055815:Young Adult
chemical_list: D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone