Current concepts surrounding neonatal hormone therapy for boys with congenital hypogonadotropic hypogonadism

References

• de Castro F, Seal R, Maggi R. ANOS1: a unified nomenclature for Kallmann syndrome 1 gene (KAL1) and anosmin-1. Brief Funct Genomics. 2017 Jul 1;16(4):205–210.
   PubMed Web of Science ®Google Scholar
• Kim JH, Seo GH, Kim GH, et al. Targeted gene panel sequencing for molecular diagnosis of Kallmann syndrome and normosmic idiopathic hypogonadotropic hypogonadism. Exp Clin Endocrinol Diabetes. 2019 Sep;127(8):538–544.
   PubMed Web of Science ®Google Scholar
• Dzemaili S, Tiemensma J, Quinton R, et al. Beyond hormone replacement: quality of life in women with congenital hypogonadotropic hypogonadism. Endocr Connect. 2017 Aug;6(6):404–412.
   PubMed Web of Science ®Google Scholar
• Fromantin M, Gineste J, Didier A, et al. [Impuberism and hypogonadism at induction into military service. Statistical study]. Probl Actuels Endocrinol Nutr. 1973 May 3;16: 179–199.
   PubMedGoogle Scholar
• Laitinen E-M, Vaaralahti K, Tommiska J, et al. Incidence, phenotypic features and molecular genetics of Kallmann syndrome in Finland. Orphanet J Rare Dis. 2011 Jun 17;6:41.
   PubMed Web of Science ®Google Scholar
• Bosch I Ara L, Katugampola H, Dattani MT. Congenital hypopituitarism during the neonatal period: epidemiology, pathogenesis, therapeutic options, and outcome. Front Pediatr. 2021 Feb 2;8:600962.
   PubMed Web of Science ®Google Scholar
• Davis SW, Castinetti F, Carvalho LR, et al. Molecular mechanisms of pituitary organogenesis: in search of novel regulatory genes. Mol Cell Endocrinol. 2010 Jul 8;323(1):4–19.
   PubMed Web of Science ®Google Scholar
• Cangiano B, Swee DS, Quinton R, et al. Genetics of congenital hypogonadotropic hypogonadism: peculiarities and phenotype of an oligogenic disease. Hum Genet. 2021 Jan;140(1):77–111.
   PubMed Web of Science ®Google Scholar
• Pitteloud N, Acierno JS, Meysing A, et al. Mutations in fibroblast growth factor receptor 1 cause both Kallmann syndrome and normosmic idiopathic hypogonadotropic hypogonadism. Proc Natl Acad Sci U S A. 2006 Apr 18;103(16):6281–6286.
   PubMed Web of Science ®Google Scholar
• McCabe MJ, Gaston-Massuet C, Tziaferi V, et al. Novel FGF8 mutations associated with recessive holoprosencephaly, craniofacial defects, and hypothalamo-pituitary dysfunction. J Clin Endocrinol Metab. 2011 Oct;96(10):E1709–18.
   PubMed Web of Science ®Google Scholar
• Men M, Wu J, Zhao Y, et al. Genotypic and phenotypic spectra of FGFR1, FGF8, and FGF17 mutations in a Chinese cohort with idiopathic hypogonadotropic hypogonadism. Fertil Steril. 2020 Jan;113(1):158–166.
   PubMed Web of Science ®Google Scholar
• Xu N, Kim HG, Bhagavath B, et al. Nasal embryonic LHRH factor (NELF) mutations in patients with normosmic hypogonadotropic hypogonadism and Kallmann syndrome. Fertil Steril. 2011 Apr;95(5):1613–20.e1-7.
   Web of Science ®Google Scholar
• Franco B, Guioli S, Pragliola A, et al. A gene deleted in Kallmann’s syndrome shares homology with neural cell adhesion and axonal path-finding molecules. Nature. 1991 Oct 10;353(6344):529–536.
   PubMed Web of Science ®Google Scholar
• Dodé C, Teixeira L, Levilliers J, et al. Kallmann syndrome: mutations in the genes encoding prokineticin-2 and prokineticin receptor-2. PLoS Genet. 2006 Oct 20;2(10):e175.
   PubMed Web of Science ®Google Scholar
• Monnier C, Dodé C, Fabre L, et al. PROKR2 missense mutations associated with Kallmann syndrome impair receptor signalling activity. Hum Mol Genet. 2009 Jan 1;18(1):75–81.
   PubMed Web of Science ®Google Scholar
• Maione L, Dwyer AA, Francou B, et al. Genetic counseling for congenital hypogonadotropic hypogonadism and Kallmann syndrome: new challenges in the era of oligogenism and next-generation sequencing. Eur J Endocrinol. 2018 Mar;178(3):R55–R80.
   PubMed Web of Science ®Google Scholar
• Mitchell AL, Dwyer A, Pitteloud N, et al. Genetic basis and variable phenotypic expression of Kallmann syndrome: towards a unifying theory. Trends Endocrinol Metab. 2011 Jul;22(7):249–258.
   PubMed Web of Science ®Google Scholar
• Boehm U, Bouloux PM, Dattani MT, et al. Expert consensus document: european Consensus Statement on congenital hypogonadotropic hypogonadism-pathogenesis, diagnosis and treatment. Nat Rev Endocrinol. 2015 Sep;11(9):547–564.
   PubMed Web of Science ®Google Scholar
• Swee DS, Quinton R. Congenital hypogonadotrophic hypogonadism: minipuberty and the case for neonatal diagnosis. Front Endocrinol (Lausanne). 2019 Feb 21;10:97.
   PubMed Web of Science ®Google Scholar
• Quinton R, Duke VM, Robertson A, et al. Idiopathic gonadotrophin deficiency: genetic questions addressed through phenotypic characterization. Clin Endocrinol (Oxf). 2001 Aug;55(2):163–174.
   PubMed Web of Science ®Google Scholar
• Bonomi M, Vezzoli V, Krausz C, et al. Characteristics of a nationwide cohort of patients presenting with isolated hypogonadotropic hypogonadism (IHH). Eur J Endocrinol. 2018 Jan;178(1):23–32.
   PubMed Web of Science ®Google Scholar
• Balasubramanian R, Crowley WF. Reproductive endocrine phenotypes relating to CHD7 mutations in humans. Am J Med Genet C Semin Med Genet. 2017 Dec;175(4):507–515.
   PubMed Web of Science ®Google Scholar
• Xu C, Cassatella D, van der Sloot AM, et al. Evaluating CHARGE syndrome in congenital hypogonadotropic hypogonadism patients harboring CHD7 variants. Genet Med. 2018 Aug;20(8):872–881.
   PubMed Web of Science ®Google Scholar
• Jongmans MCJ, Admiraal RJ, Van Der Donk KP, et al. CHARGE syndrome: the phenotypic spectrum of mutations in the CHD7 gene. J Med Genet. 2006 Apr;43(4):306–314.
   PubMed Web of Science ®Google Scholar
• Webb EA, Dattani MT. Septo-optic dysplasia. Eur J Hum Genet. 2010 Apr;18(4):393–397.
   PubMed Web of Science ®Google Scholar
• Raivio T, Avbelj M, McCabe MJ, et al. Genetic overlap in Kallmann syndrome, combined pituitary hormone deficiency, and septo-optic dysplasia. J Clin Endocrinol Metab. 2012 Apr;97(4):E694–9.
   PubMed Web of Science ®Google Scholar
• Kevelam SHG, Van Harssel JJT, Van Der Zwaag B, et al. A patient with a mild holoprosencephaly spectrum phenotype and heterotaxy and a 1.3Mb deletion encompassing GLI2. Am J Med Genet A. 2012 Jan;158A(1):166–173.
   PubMed Web of Science ®Google Scholar
• Dwyer AA, Tiemensma J, Quinton R, et al. Adherence to treatment in men with hypogonadotrophic hypogonadism. Clin Endocrinol (Oxf). 2017 Mar;86(3):377–383.
   PubMed Web of Science ®Google Scholar
• Varimo T, Hero M, Laitinen EM, et al. Health-related quality of life in male patients with congenital hypogonadotropic hypogonadism. Clin Endocrinol (Oxf). 2015 Jul;83(1):141–143.
   PubMed Web of Science ®Google Scholar
• Quinton R. Phenotypic aspect of Kallmann’s syndrome [MD dissertation]. University of Cambridge; 2000.
   Google Scholar
• Sedlmeyer IL, Palmert MR. Delayed puberty: analysis of a large case series from an academic center. J Clin Endocrinol Metab. 2002 Apr;87(4):1613–1620.
   PubMed Web of Science ®Google Scholar
• Harrington J, Palmert MR. Distinguishing constitutional delay of growth and puberty from isolated hypogonadotropic hypogonadism: critical appraisal of available diagnostic tests. J Clin Endocrinol Metab. 2012 Sep;97(9):3056–3067.
   PubMed Web of Science ®Google Scholar
• Dunkel L, Quinton R. Transition in endocrinology: induction of puberty. Eur J Endocrinol. 2014 Jun;170(6):R229–39.
   PubMed Web of Science ®Google Scholar
• Varimo T, Miettinen PJ, Känsäkoski J, et al. Congenital hypogonadotropic hypogonadism, functional hypogonadotropism or constitutional delay of growth and puberty? An analysis of a large patient series from a single tertiary center. Hum Reprod. 2017 Jan;32(1):147–153.
   PubMed Web of Science ®Google Scholar
• Chan YM, Lippincott MF, Sales Barroso P, et al. Using Kisspeptin to predict pubertal outcomes for youth with pubertal delay. J Clin Endocrinol Metab. 2020 Aug 1;105(8):e2717–e2725.
   PubMed Web of Science ®Google Scholar
• Dwyer AA, Jayasena CN, Quinton R. Congenital hypogonadotropic hypogonadism: implications of absent mini-puberty. Minerva Endocrinol. 2016 Jun;41(2):188–195.
   PubMed Web of Science ®Google Scholar
• Rey RA, Grinspon RP. Normal male sexual differentiation and aetiology of disorders of sex development. Best Pract Res Clin Endocrinol Metab. 2011 Apr;25(2):221–238.
   PubMed Web of Science ®Google Scholar
• Bay K, Main KM, Toppari J, et al. Testicular descent: INSL3, testosterone, genes and the intrauterine milieu. Nat Rev Urol. 2011 Apr;8(4):187–196.
   PubMed Web of Science ®Google Scholar
• Koskenniemi JJ, Virtanen HE, Wohlfahrt-Veje C, et al. Postnatal changes in testicular position are associated with IGF-I and function of sertoli and leydig cells. J Clin Endocrinol Metab. 2018 Apr 1;103(4):1429–1437.
   PubMed Web of Science ®Google Scholar
• Harrison SM, Bush NC, Wang Y, et al. Insulin-like Peptide 3 (INSL3) serum concentration during human male fetal life. Front Endocrinol (Lausanne). 2019 Sep 4;10:596.
   PubMed Web of Science ®Google Scholar
• O’Shaughnessy PJ, Baker PJ, Monteiro A, et al. Developmental changes in human fetal testicular cell numbers and messenger ribonucleic acid levels during the second trimester. J Clin Endocrinol Metab. 2007 Dec;92(12):4792–4801.
   PubMed Web of Science ®Google Scholar
• Bouvattier C, Maione L, Bouligand J, et al. Neonatal gonadotropin therapy in male congenital hypogonadotropic hypogonadism. Nat Rev Endocrinol. 2011 Oct 18;8(3):172–182.
   PubMed Web of Science ®Google Scholar
• Winter JSD, Hughes IA, Reyes FI, et al. Pituitary-gonadal relations in infancy: 2. Patterns of serum gonadal steroid concentrations in man from birth to two years of age. J Clin Endocrinol Metab. 1976 Apr;42(4):679–686.
   PubMed Web of Science ®Google Scholar
• Forest MG, Cathiard AM, Bertrand JA. Evidence of testicular activity in early infancy. J Clin Endocrinol Metab. 1973 Jul;37(1):148–151.
   PubMed Web of Science ®Google Scholar
• Johannsen TH, Main KM, Ljubicic ML, et al. Sex-differences in reproductive hormones during mini-puberty in infants with normal and disordered sex development. J Clin Endocrinol Metab. 2018 Aug 1;103(8):3028–3037.
   PubMed Web of Science ®Google Scholar
• Chemes HE. Infancy is not a quiescent period of testicular development. Int J Androl. 2001 Feb;24(1):2–7.
   PubMedGoogle Scholar
• Rey RA, Musse M, Venara M, et al. Ontogeny of the androgen receptor expression in the fetal and postnatal testis: its relevance on sertoli cell maturation and the onset of adult spermatogenesis. Microsc Res Tech. 2009 Nov;72(11):787–795.
   PubMed Web of Science ®Google Scholar
• Chemes HE, Rey RA, Nistal M, et al. Physiological androgen insensitivity of the fetal, neonatal, and early infantile testis is explained by the ontogeny of the androgen receptor expression in sertoli cells. J Clin Endocrinol Metab. 2008 Nov;93(11):4408–4412.
   PubMed Web of Science ®Google Scholar
• Aksglaede L, Sørensen K, Boas M, et al. Changes in anti-Müllerian hormone (AMH) throughout the life span: a population-based study of 1027 healthy males from birth (cord blood) to the age of 69 years. J Clin Endocrinol Metab. 2010 Dec;95(12):5357–5364.
   PubMed Web of Science ®Google Scholar
• Boas M, Boisen KA, Virtanen HE, et al. Postnatal penile length and growth rate correlate to serum testosterone levels: a longitudinal study of 1962 normal boys. Eur J Endocrinol. 2006 Jan;154(1):125–129.
   PubMed Web of Science ®Google Scholar
• Cortes D, Müller J, Skakkebaek NE. Proliferation of Sertoli cells during development of the human testis assessed by stereological methods. Int J Androl. 1987 Aug;10(4):589–596.
   PubMedGoogle Scholar
• Russell LD, Ren HP, Hikim IS, et al. A comparative study in twelve mammalian species of volume densities, volumes, and numerical densities of selected testis components, emphasizing those related to the Sertoli cell. Am J Anat. 1990 May;188(1):21–30.
   PubMedGoogle Scholar
• Stamou MI, Varnavas P, Kentrou M, et al. Isolated GNRH deficiency: genotypic and phenotypic characteristics of the genetically heterogeneous Greek population. Eur J Endocrinol. 2017 Mar;176(3):L1–L5.
   PubMed Web of Science ®Google Scholar
• Mann DR, Gould KG, Collins DC, et al. Blockade of neonatal activation of the pituitary-testicular axis: effect on peripubertal luteinizing hormone and testosterone secretion and on testicular development in male monkeys. J Clin Endocrinol Metab. 1989 Mar;68(3):600–607.
   PubMed Web of Science ®Google Scholar
• Kuiri-Hänninen T, Koskenniemi J, Dunkel L, et al. Postnatal testicular activity in healthy boys and boys with cryptorchidism. Front Endocrinol (Lausanne). 2019 Jul 23;10:489.
   PubMed Web of Science ®Google Scholar
• Papadimitriou DT, Chrysis D, Nyktari G, et al. Replacement of male mini-puberty. J Endocr Soc. 2019 May 9;3(7):1275–1282.
   PubMed Web of Science ®Google Scholar
• Braslavsky D, Grinspon RP, Ballerini MG, et al. Hypogonadotropic hypogonadism in infants with congenital hypopituitarism: a challenge to diagnose at an early stage. Horm Res Paediatr. 2015;84(5):289–297.
   PubMed Web of Science ®Google Scholar
• Suomi AM, Main KM, Kaleva M, et al. Hormonal changes in 3-month-old cryptorchid boys. J Clin Endocrinol Metab. 2006 Mar;91(3):953–958.
   PubMed Web of Science ®Google Scholar
• Acerini CL, Miles HL, Dunger DB, et al. The descriptive epidemiology of congenital and acquired cryptorchidism in a UK infant cohort. Arch Dis Child. 2009 Nov;94(11):868–872.
   PubMed Web of Science ®Google Scholar
• Berkowitz GS, Lapinski RH, Dolgin SE, et al. Prevalence and natural history of cryptorchidism. Pediatrics. 1993 Jul;92(1):44–49.
   PubMed Web of Science ®Google Scholar
• John Radcliffe Hospital Cryptorchidism Study Group. Cryptorchidism: a prospective study of 7500 consecutive male births, 1984-8. John Radcliffe Hospital Cryptorchidism Study Group. Arch Dis Child. 1992 Jul;67(7):892–899.
   PubMed Web of Science ®Google Scholar
• Ghirri P, Ciulli C, Vuerich M, et al. Incidence at birth and natural history of cryptorchidism: a study of 10,730 consecutive male infants. J Endocrinol Invest. 2002 Sep;25(8):709–715.
   PubMed Web of Science ®Google Scholar
• Sijstermans K, Hack WWM, Meijer RW, et al. The frequency of undescended testis from birth to adulthood: a review. Int J Androl. 2008 Feb;31(1):1–11.
   PubMedGoogle Scholar
• Quinton R, Mamoojee Y, Jayasena CN, et al. Society for Endocrinology UK guidance on the evaluation of suspected disorders of sexual development: emphasizing the opportunity to predict adolescent pubertal failure through a neonatal diagnosis of absent minipuberty. Clin Endocrinol (Oxf). 2017 Feb;86(2):305–306.
   PubMed Web of Science ®Google Scholar
• Martin Ritzén E, Bergh A, Bjerknes R, et al. Nordic consensus on treatment of undescended testes. Acta Paediatr. 2007 May;96(5):638–643.
   PubMed Web of Science ®Google Scholar
• Ahmed SF, Achermann JC, Arlt W, et al. Society for Endocrinology UK guidance on the initial evaluation of an infant or an adolescent with a suspected disorder of sex development (Revised 2015). Clin Endocrinol (Oxf). 2016 May;84(5):771–788.
   PubMed Web of Science ®Google Scholar
• Kolon TF, Herndon CDA, Baker LA, et al. Evaluation and treatment of Cryptorchidism: AUA guideline. J Urol. 2014 Aug;192(2):337–345.
   PubMed Web of Science ®Google Scholar
• Hatipoǧlu N, Kurtoǧlu S. Micropenis: etiology, diagnosis and treatment approaches. J Clin Res Pediatr Endocrinol. 2013;5(4):217–223.
   PubMed Web of Science ®Google Scholar
• Main KM, Schmidt IM, Toppari J, et al. Early postnatal treatment of hypogonadotropic hypogonadism with recombinant human FSH and LH. Eur J Endocrinol. 2002 Jan;146(1):75–79.
   PubMed Web of Science ®Google Scholar
• Bougnères P, François M, Pantalone L, et al. Effects of an early postnatal treatment of hypogonadotropic hypogonadism with a continuous subcutaneous infusion of recombinant follicle-stimulating hormone and luteinizing hormone. J Clin Endocrinol Metab. 2008 Jun;93(6):2202–2205.
   PubMed Web of Science ®Google Scholar
• Sarfati J, Bouvattier C, Bry-Gauillard H, et al. Kallmann syndrome with FGFR1 and KAL1 mutations detected during fetal life. Orphanet J Rare Dis. 2015 Jun 9;10:71.
   PubMed Web of Science ®Google Scholar
• Swee DS, Quinton R, Maggi R. Recent advances in understanding and managing Kallmann syndrome. Fac Rev. 2021 Apr 13;10:37.
   PubMedGoogle Scholar
• Rohayem J, Hauffa BP, Zacharin M, et al. 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-. Clin Endocrinol (Oxf). 2017 Jan;86(1):75–87.
   PubMed Web of Science ®Google Scholar
• Stoupa A, Samara-Boustani D, Flechtner I, et al. Efficacy and safety of continuous subcutaneous infusion of recombinant human gonadotropins for congenital micropenis during early infancy. Horm Res Paediatr. 2017;87(2):103–110.
   PubMed Web of Science ®Google Scholar
• Lambert A-S, Bougneres P. Growth and descent of the testes in infants with hypogonadotropic hypogonadism receiving subcutaneous gonadotropin infusion. Int J Pediatr Endocrinol. 2016;2016:13.
   PubMedGoogle Scholar
• Schaison G, Young J, Pholsena M, et al. Failure of combined follicle-stimulating hormone-testosterone administration to initiate and/or maintain spermatogenesis in men with hypogonadotropic hypogonadism. J Clin Endocrinol Metab. 1993 Dec;77(6):1545–1549.
   PubMed Web of Science ®Google Scholar
• Kohva E, Huopio H, Hietamäki J, et al. Treatment of gonadotropin deficiency during the first year of life: long-term observation and outcome in five boys. Hum Reprod. 2019 May 1;34(5):863–871.
   PubMed Web of Science ®Google Scholar
• Kollin C, Stukenborg JB, Nurmio M, et al. Boys with undescended testes: endocrine, volumetric and morphometric studies on testicular function before and after orchidopexy at nine months or three years of age. J Clin Endocrinol Metab. 2012 Dec;97(12):4588–4595.
   PubMed Web of Science ®Google Scholar
• Liu Z, Mao J, Xu H, et al. Gonadotropin-induced spermatogenesis in CHH patients with cryptorchidism. Int J Endocrinol. 2019 Dec 18;2019:6743489.
   PubMed Web of Science ®Google Scholar
• Verkauskas G, Malcius D, Eidukaite A, et al. Prospective study of histological and endocrine parameters of gonadal function in boys with cryptorchidism. J Pediatr Urol. 2016 Aug;12(4):238.e1–6.
   Google Scholar
• Zivkovic D, Bica DTG, Hadziselimovic F. Relationship between adult dark spermatogonia and secretory capacity of Leydig cells in cryptorchidism. BJU Int. 2007 Nov;100(5):1147–1149.
   PubMed Web of Science ®Google Scholar
• Santhakumar A, Miller M, Quinton R. Pubertal induction in adult males with isolated hypogonadotropic hypogonadism using long-acting intramuscular testosterone undecanoate 1-g depot (Nebido). Clin Endocrinol (Oxf). 2014 Jan;80(1):155–157.
   PubMed Web of Science ®Google Scholar
• Sharma S, Shah R, Patil V, et al. Gonadotropins for testicular descent in cryptorchid congenital hypogonadotropic hypogonadism males beyond infancy. J Pediatr Endocrinol Metab. 2021 Apr 26;34(7):917–924.
   PubMed Web of Science ®Google Scholar
• Dunkel L, Taskinen S, Hovatta O, et al. Germ cell apoptosis after treatment of cryptorchidism with human chorionic gonadotropin is associated with impaired reproductive function in the adult. J Clin Invest. 1997 Nov 1;100(9):2341–2346.
   PubMed Web of Science ®Google Scholar
• Kirk JM, Savage MO, Grant DB, et al. Gonadal function and response to human chorionic and menopausal gonadotrophin therapy in male patients with idiopathic hypogonadotrophic hypogonadism. Clin Endocrinol (Oxf). 1994 Jul;41(1):57–63.
   PubMed Web of Science ®Google Scholar
• Liu L, Banks SM, Barnes KM, et al. Two-year comparison of testicular responses to pulsatile gonadotropin-releasing hormone and exogenous gonadotropins from the inception of therapy in men with isolated hypogonadotropic hypogonadism. J Clin Endocrinol Metab. 1988 Dec;67(6):1140–1145.
   PubMed Web of Science ®Google Scholar
• Büchter D, Behre HM, Kliesch S, et al. Pulsatile GnRH or human chorionic gonadotropin/human menopausal gonadotropin as effective treatment for men with hypogonadotropic hypogonadism: a review of 42 cases. Eur J Endocrinol. 1998 Sep;139(3):298–303.
   PubMed Web of Science ®Google Scholar
• Pitteloud N, Hayes FJ, Dwyer A, et al. Predictors of outcome of long-term GnRH therapy in men with idiopathic hypogonadotropic hypogonadism. J Clin Endocrinol Metab. 2002 Sep;87(9):4128–4136.
   PubMed Web of Science ®Google Scholar
• Liu PY, Baker HWG, Jayadev V, et al. Induction of spermatogenesis and fertility during gonadotropin treatment of Gonadotropin-deficient infertile men: predictors of fertility outcome. J Clin Endocrinol Metab. 2009 Mar;94(3):801–808.
   PubMed Web of Science ®Google Scholar
• Burris AS, Rodbard HW, Winters SJ, et al. Gonadotropin therapy in men with isolated hypogonadotropic hypogonadism: the response to human chorionic gonadotropin is predicted by initial testicular size. J Clin Endocrinol Metab. 1988 Jun;66(6):1144–1151.
   PubMed Web of Science ®Google Scholar
• Raivio T, Toppari J, Perheentupa A, et al. Treatment of prepubertal gonadotrophin-deficient boys with recombinant human follicle-stimulating hormone. Lancet. 1997 Jul 26;350(9073):263–264.
   PubMed Web of Science ®Google Scholar
• Smith N, Quinton R. Kallmann syndrome. BMJ. 2012 Dec 3;345:e6971.
   PubMedGoogle Scholar
• Budych K, Helms TM, Schultz C. How do patients with rare diseases experience the medical encounter? Exploring role behavior and its impact on patient-physician interaction. Health Policy. 2012 May;105(2–3):154–164.
   PubMed Web of Science ®Google Scholar
• Hannemann-Weber H, Kessel M, Schultz C. Research performance of centers of expertise for rare diseases-The influence of network integration, internal resource access and operational experience. Health Policy. 2012 May;105(2–3):138–145.
   PubMed Web of Science ®Google Scholar
• Quaynor SD, Bosley ME, Duckworth CG, et al. Targeted next generation sequencing approach identifies eighteen new candidate genes in normosmic hypogonadotropic hypogonadism and Kallmann syndrome. Mol Cell Endocrinol. 2016 Dec 5;437:86–96.
   PubMed Web of Science ®Google Scholar
• Dwyer AA, Quinton R, Morin D, et al. Identifying the unmet health needs of patients with congenital hypogonadotropic hypogonadism using a web-based needs assessment: implications for online interventions and peer-to-peer support. Orphanet J Rare Dis. 2014 Jun 11;9:83.
   PubMed Web of Science ®Google Scholar
• Palmert MR, Dunkel L. Delayed Puberty. N Engl J Med. 2012 Feb 2;366(5):443–453.
   PubMed Web of Science ®Google Scholar
• Graber JA, Seeley JR, Brooks-Gunn J, et al. Is pubertal timing associated with psychopathology in young adulthood? J Am Acad Child Adolesc Psychiatry. 2004 Jun;43(6):718–726.
   PubMed Web of Science ®Google Scholar
• Shiraishi K, Oka S, Matsuyama H. Assessment of quality of life during gonadotrophin treatment for male hypogonadotrophic hypogonadism. Clin Endocrinol (Oxf). 2014 Aug;81(2):259–265.
   PubMed Web of Science ®Google Scholar
• Pitteloud N, Hayes FJ, Boepple PA, et al. The role of prior pubertal development, biochemical markers of testicular maturation, and genetics in elucidating the phenotypic heterogeneity of idiopathic hypogonadotropic hypogonadism. J Clin Endocrinol Metab. 2002 Jan;87(1):152–160.
   PubMed Web of Science ®Google Scholar
• Swee DS, Quinton R. Managing congenital hypogonadotrophic hypogonadism: a contemporary approach directed at optimizing fertility and long-term outcomes in males. Ther Adv Endocrinol Metab. 2019 Feb 10;10:2042018819826889.
   Web of Science ®Google Scholar
• Andersson AM, Müller J, Skakkebæk NE. Different roles of prepubertal and postpubertal germ cells and sertoli cells in the regulation of serum inhibin B levels. J Clin Endocrinol Metab. 1998 Dec;83(12):4451–4458.
   PubMed Web of Science ®Google Scholar
• Raivio T, Wikström AM, Dunkel L. Treatment of gonadotropin-deficient boys with recombinant human FSH: long-term observation and outcome. Eur J Endocrinol. 2007 Jan;156(1):105–111.
   PubMed Web of Science ®Google Scholar
• Dwyer AA, Sykiotis GP, Hayes FJ, et al. Trial of recombinant follicle-stimulating hormone pretreatment for GnRH-induced fertility in patients with congenital hypogonadotropic hypogonadism. J Clin Endocrinol Metab. 2013 Nov;98(11):E1790–5.
   PubMed Web of Science ®Google Scholar
• Chen Y, Sun T, Niu Y, et al. Correlations among genotype and outcome in chinese male patients with congenital hypogonadotropic hypogonadism under HCG treatment. J Sex Med. 2020 Apr;17(4):645–657.
   PubMed Web of Science ®Google Scholar
• Vicari E, Mongioì A, Calogero AE, et al. Therapy with human chorionic gonadotrophin alone induces spermatogenesis in men with isolated hypogonadotrophic hypogonadism‐long‐term follow‐up. Int J Androl. 1992 Aug;15(4):320–329.
   PubMedGoogle Scholar
• Yang L, Zhang SX, Dong Q, et al. Application of hormonal treatment in hypogonadotropic hypogonadism: more than ten years experience. Int Urol Nephrol. 2012 Apr;44(2):393–399.
   PubMed Web of Science ®Google Scholar
• Ortaç M, Hıdır M, Çilesiz NC, et al. Efficacy of follitropin-alpha versus human menopausal gonadotropin for male patients with congenital hypogonadotropic hypogonadism. Turk J Urol. 2020 Nov 29;46(1):13–17.
   PubMed Web of Science ®Google Scholar
• Dwyer AA, Quinton R, Pitteloud N, et al. Psychosexual development in men with congenital hypogonadotropic hypogonadism on long-term treatment: a mixed methods study. Sex Med. 2015 Mar;3(1):32–41.
   PubMed Web of Science ®Google Scholar