Approach to the male patient with congenital hypogonadotropic hypogonadism

Journal of Clinical Endocrinology and Metabolism

Volumn 97, Issue 3, 2012, Pages 707-718

  Young, Jacques ^a,b,c  

^a UNIVERSITÉ PARIS SACLAY   (France)

^b BICÊTRE HOSPITAL   (France)

^c Institut National de la Santé   (France)

Author keywords

[No Author keywords available]

Indexed keywords

ANDROSTANOLONE; CHORIONIC GONADOTROPIN; FOLLITROPIN; GONADORELIN; GONADOTROPIN; INHIBIN B; LUTEINIZING HORMONE; TESTOSTERONE; TESTOSTERONE ENANTATE; TESTOSTERONE ESTER; TESTOSTERONE UNDECANOATE;

ANOSMIA; CLINICAL FEATURE; DELAYED PUBERTY; DIAGNOSTIC VALUE; DIFFERENTIAL DIAGNOSIS; DRUG COST; DRUG DOSE INCREASE; DRUG EFFICACY; ECHOGRAPHY; FOLLITROPIN BLOOD LEVEL; FOLLITROPIN RELEASE; GENE MUTATION; GENETIC COUNSELING; GONADOTROPIN BLOOD LEVEL; HORMONE DETERMINATION; HORMONE SUBSTITUTION; HUMAN; HYPOGONADOTROPIC HYPOGONADISM; KALLMANN SYNDROME; LOW DRUG DOSE; LUTEINIZING HORMONE BLOOD LEVEL; LUTEINIZING HORMONE RELEASE; PATIENT COMPLIANCE; PRIORITY JOURNAL; REVIEW; TESTIS SIZE; TESTOSTERONE BLOOD LEVEL;

ADOLESCENT; DIAGNOSIS, DIFFERENTIAL; GONADOTROPIN-RELEASING HORMONE; GONADOTROPINS; HORMONE REPLACEMENT THERAPY; HUMANS; HYPOGONADISM; KALLMANN SYNDROME; MALE; TESTOSTERONE;

EID: 84858038527     PISSN: 0021972X     EISSN: 19457197     Source Type: Journal    
DOI: 10.1210/jc.2011-1664     Document Type: Review

References (79)

1. Sedlmeyer IL, Palmert MR 2002 Delayed puberty: analysis of a large case series from an academic center. J Clin Endocrinol Metab 87: 1613-1620 (Pubitemid 34615247)
2. Bianco SD, Kaiser UB 2009 The genetic and molecular basis of idiopathic hypogonadotropic hypogonadism. Nat Rev Endocrinol 5:569-576
3. Brioude F, Bouligand J, Trabado S, Francou B, Salenave S, Kamenicky P, Brailly-Tabard S, Chanson P, Guiochon-Mantel A, Young J 2010 Non-syndromic congenital hypogonadotropic hypogonadism: clinical presentation and genotype-phenotype relationships. Eur J Endocrinol 162:835-851
4. Dodé C, Hardelin JP 2010 Clinical genetics of Kallmann syndrome. Ann Endocrinol (Paris) 71:149-157
5. Mitchell AL, Dwyer A, Pitteloud N, Quinton R 2011 Genetic basis and variable phenotypic expression of Kallmann syndrome: towards a unifying theory. Trends Endocrinol Metab 22:249-258
6. Bojesen A, Juul S, Gravholt CH 2003 Prenatal and postnatal prevalence of Klinefelter syndrome: a national registry study. J Clin Endocrinol Metab 88:622-626 (Pubitemid 36207801)
7. Fromantin M, Gineste J, Didier A, Rouvier J 1973 [Impuberism and hypogonadism at induction into military service. Statistical study.] Probl Actuels Endocrinol Nutr 16:179-199
8. Filippi G 1986 Klinefelter's syndrome in Sardinia. Clinical report of 265 hypogonadic males detected at the time of military check-up. Clin Genet 30:276-284 (Pubitemid 17176284)
9. Farooqi IS, Wangensteen T, Collins S, Kimber W, Matarese G, Keogh JM, Lank E, Bottomley B, Lopez-Fernandez J, Ferraz-Amaro I, Dattani MT, Ercan O, Myhre AG, Retterstol L, Stanhope R, Edge JA, McKenzie S, Lessan N, Ghodsi M, De Rosa V, Perna F, Fontana S, Barroso I, Undlien DE, O'Rahilly S 2007 Clinical and molecular genetic spectrum of congenital deficiency of the leptin receptor. N Engl J Med 356:237-247 (Pubitemid 46143227)
10. Lin L, Gu WX, Ozisik G, To WS, Owen CJ, Jameson JL, Achermann JC 2006 Analysis of DAX1 (NR0B1) and steroidogenic factor-1 (NR5A1) in children and adults with primary adrenal failure: ten years' experience. J Clin Endocrinol Metab 91:3048-3054 (Pubitemid 44271754)
11. Netchine I, Sobrier ML, Krude H, Schnabel D, Maghnie M, Marcos E, Duriez B, Cacheux V, Moers A, Goossens M, Grüters A, Amselem S 2000 Mutations in LHX3 result in a new syndrome revealed by combined pituitary hormone deficiency. Nat Genet 25:182-186 (Pubitemid 30394989)
12. Pinto G, Abadie V, Mesnage R, Blustajn J, Cabrol S, Amiel J, Hertz- Pannier L, Bertrand AM, Lyonnet S, Rappaport R, Netchine I 2005 CHARGE syndrome includes hypogonadotropic hypogonadism and abnormal olfactory bulb development. J Clin Endocrinol Metab 90:5621-5626
13. Rottembourg D, Linglart A, Adamsbaum C, Lahlou N, Teinturier C, Bougnères P, Carel JC 2008 Gonadotrophic status in adolescents with pituitary stalk interruption syndrome. Clin Endocrinol (Oxf) 69:105-111 (Pubitemid 351847267)
14. Reynaud R, Gueydan M, Saveanu A, Vallette-Kasic S, Enjalbert A, Brue T, Barlier A 2006 Genetic screening of combined pituitary hormone deficiency: experience in 195 patients. J Clin Endocrinol Metab 91:3329-3336 (Pubitemid 44402099)
15. Carlson HE 2011 Approach to the patient with gynecomastia. J Clin Endocrinol Metab 96:15-21
16. Trabado S, Maione L, Salenave S, Baron S, Galland F, Bry-Gauillard H, Guiochon-Mantel A, Chanson P, Pitteloud N, Sinisi AA, Brailly-Tabard S, Young J 2011 Estradiol levels in men with congenital hypogonadotropic hypogonadism and the effects of different modalities of hormonal treatment. Fertil Steril 95: 2324-2329, 2329.e1-33
17. Sikaris K, McLachlan RI, Kazlauskas R, de Kretser D, Holden CA, Handelsman DJ 2005 Reproductive hormone reference intervals for healthy fertile young men: evaluation of automated platform assays. J Clin Endocrinol Metab 90:5928-5936 (Pubitemid 41606507)
18. Wartofsky L, Handelsman DJ 2010 Standardization of hormonal assays for the 21st century. J Clin Endocrinol Metab 95:5141-5143
19. Lanfranco F, Kamischke A, Zitzmann M, Nieschlag E 2004 Klinefelter's syndrome. Lancet 364:273-283 (Pubitemid 38942818)
20. El Amm M, Brailly S, Bauduceau B, Young J 2007 Klinefelter syndrome. In: Chanson P, Young J, eds. Endocrinology, treatise. Paris: Flammarion; 622-627
21. Barkan AL, Reame NE, Kelch RP, Marshall JC 1985 Idiopathic hypogonadotropic hypogonadism in men: dependence of the hormone responses to gonadotropin-releasing hormone (GnRH) on the magnitude of the endogenous GnRH secretory defect. J Clin Endocrinol Metab 61:1118-1125 (Pubitemid 16186712)
22. Lofrano-Porto A, Barra GB, Giacomini LA, Nascimento PP, Latronico AC, Casulari LA, da Rocha Neves Fde A 2007 Luteinizing hormone β mutation and hypogonadism in men and women. N Engl J Med 357:897-904 (Pubitemid 47347323)
23. Kottler ML, Chou YY, Chabre O, Richard N, Polge C, Brailly-Tabard S, Chanson P, Guiochon-Mantel A, Huhtaniemi I, Young J 2010 A new FSH β mutation in a 29-year-old woman with primary amenorrhea and isolated FSH deficiency: functional characterization and ovarian response to human recombinant FSH. Eur J Endocrinol 162:633-641
24. Salenave S, Chanson P, Bry H, Pugeat M, Cabrol S, Carel JC, Murat A, Lecomte P, Brailly S, Hardelin JP, Dodé C, Young J 2008 Kallmann's syndrome: a comparison of the reproductive phenotypes in men carrying KAL1 and FGFR1/KAL2 mutations. J Clin Endocrinol Metab 93:758-763 (Pubitemid 351398550)
25. Bouligand J, Ghervan C, Tello JA, Brailly-Tabard S, Salenave S, Chanson P, Lombès M, Millar RP, Guiochon-Mantel A, Young J 2009 Isolated familial hypogonadotropic hypogonadism and a GNRH1 mutation. N Engl J Med 360:2742-2748
26. Sarfati J, Guiochon-Mantel A, Rondard P, Arnulf I, Garcia-Piñero A, Wolczynski S, Brailly-Tabard S, Bidet M, Ramos-Arroyo M, Mathieu M, Lienhardt-Roussie A, Morgan G, Turki Z, Bremont C, Lespinasse J, Du Boullay H, Chabbert-Buffet N, Jacquemont S, Reach G, De Talence N, Tonella P, Conrad B, Despert F, Delobel B, Brue T, Bouvattier C, Cabrol S, Pugeat M, Murat A, Bouchard P, Hardelin JP, Dodé C, Young J 2010 A comparative phenotypic study of Kallmann syndrome patients carrying monoallelic and biallelic mutations in the prokineticin 2 or prokineticin receptor 2 genes. J Clin Endocrinol Metab 95:659-669
27. de Roux N, Young J, Misrahi M, Genet R, Chanson P, Schaison G, Milgrom E 1997 A family with hypogonadotropic hypogonadism and mutations in the gonadotropin-releasing hormone receptor. N Engl J Med 337:1597-1602 (Pubitemid 27509763)
28. Fideleff HL, Boquete HR, Suárez MG, Azaretzky M 2009 Prolactinoma in children and adolescents. Horm Res 72:197-205
29. Jagannathan J, Dumont AS, Jane Jr JA 2006 Diagnosis and management of pediatric sellar lesions. Front Horm Res 34:83-104 (Pubitemid 43265655)
30. Ozgör B, Selimoolu MA 2010 Coeliac disease and reproductive disorders. Scand J Gastroenterol 45:395-402
31. Hackney AC 2008 Effects of endurance exercise on the reproductive system of men: the "exercise-hypogonadal male condition." J Endocrinol Invest 31:932-938
32. Young J 2007 [Endocrine consequences of hemochromatosis]. Presse Med 36:1319-1325
33. Spadoni GL, Cianfarani S 2010 Bone age assessment in the workup of children with endocrine disorders. Horm Res Paediatr 73:2-5
34. De Luca F, Argente J, Cavallo L, Crowne E, Delemarre-Van de Waal HA, De Sanctis C, Di Maio S, Norjavaara E, Oostdijk W, Severi F, Tonini G, Trifirò G, Voorhoeve PG, Wu F 2001 Management of puberty in constitutional delay of growth and puberty. International Workshop on Management of Puberty for Optimum Auxological Results. J Pediatr Endocrinol Metab 14(Suppl 2):953-957
35. Segal TY, Mehta A, Anazodo A, Hindmarsh PC, Dattani MT 2009 Role of gonadotropin-releasing hormone and human chorionic gonadotropin stimulation tests in differentiating patients with hypogonadotropic hypogonadism from those with constitutional delay of growth and puberty. J Clin Endocrinol Metab 94:780-785
36. Coutant R, Biette-Demeneix E, Bouvattier C, Bouhours-Nouet N, Gatelais F, Dufresne S, Rouleau S, Lahlou N 2010 Baseline inhibin B and anti-Mullerian hormone measurements for diagnosis of hypogonadotropic hypogonadism (HH) in boys with delayed puberty. J Clin Endocrinol Metab 95:5225-5232
37. Grinspon RP, Ropelato MG, Gottlieb S, Keselman A, Martínez A, Ballerini MG, Domené HM, Rey RA 2010 Basal follicle-stimulating hormone and peak gonadotropin levels after gonadotropin-releasing hormone infusion show high diagnostic accuracy in boys with suspicion of hypogonadotropic hypogonadism. J Clin Endocrinol Metab 95:2811-2818
38. Pitteloud N, Hayes FJ, Boepple PA, DeCruz S, Seminara SB, MacLaughlin DT, Crowley Jr WF 2002 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 87: 152-160 (Pubitemid 34084685)
39. Kaplan JD, Bernstein JA, Kwan A, Hudgins L 2010 Clues to an early diagnosis of Kallmann syndrome. Am J Med Genet A 152A:2796-2801
40. Dodé C, Levilliers J, Dupont JM, De Paepe A, Le DÛ N, Soussi- Yanicostas N, Coimbra RS, Delmaghani S, Compain-Nouaille S, Baverel F, Pêcheux C, Le Tessier D, Cruaud C, Delpech M,Speleman F, Vermeulen S, Amalfitano A, Bachelot Y, Bouchard P, Cabrol S, Carel JC, Delemarre-van de Waal H, Goulet-Salmon B, Kottler ML, Richard O, Sanchez-Franco F, Saura R, Young J, Petit C, Hardelin JP 2003 Loss-of-function mutations in FGFR1 cause autosomal dominant Kallmann syndrome. Nat Genet 33:463-465
41. Dodé C, Teixeira L, Levilliers J, Fouveaut C, Bouchard P, Kottler ML, Lespinasse J, Lienhardt-Roussie A, Mathieu M, Moerman A, Morgan G, Murat A, Toublanc JE, Wolczynski S, Delpech M, Petit C, Young J, Hardelin JP 2006 Kallmann syndrome: mutations in the genes encoding prokineticin-2 and prokineticin receptor-2. PLoS Genet 2:e175
42. Falardeau J, Chung WC, Beenken A, Raivio T, Plummer L, Sidis Y, Jacobson-Dickman EE, Eliseenkova AV, Ma J, Dwyer A, Quinton R, Na S, Hall JE, Huot C, Alois N, Pearce SH, Cole LW, Hughes V, Mohammadi M, Tsai P, Pitteloud N 2008 Decreased FGF8 signaling causes deficiency of gonadotropin-releasing hormone in humans and mice. J Clin Invest 118:2822-2831
43. Liu PY, Baker HW, Jayadev V, Zacharin M, Conway AJ, Handelsman DJ 2009 Induction of spermatogenesis and fertility during gonadotropin treatment of gonadotropin-deficient infertile men: predictors of fertility outcome. J Clin Endocrinol Metab 94:801-808
44. Hardelin JP, Levilliers J, Young J, Pholsena M, Legouis R, Kirk J, Bouloux P, Petit C, Schaison G 1993 Xp22.3 deletions in isolated familial Kallmann's syndrome. J Clin Endocrinol Metab 76:827-831 (Pubitemid 23110822)
45. Ritzén EM 2008 Undescended testes: a consensus on management. Eur J Endocrinol 159(Suppl 1):S87-S90
46. Georgopoulos NA, Koika V, Galli-Tsinopoulou A, Spiliotis BE, Adonakis G, Keramida MK, Sgourou A, Koufogiannis KD, Papachatzopoulou A, Papavassiliou AG, Kourounis G, Vagenakis GA 2007 Renal dysgenesis and KAL1 gene defects in patients with sporadic Kallmann syndrome. Fertil Steril 88:1311-1317 (Pubitemid 350030067)
47. Bailleul-Forestier I, Gros C, Zenaty D, Bennaceur S, Leger J, de Roux N 2010 Dental agenesis in Kallmann syndrome individuals with FGFR1 mutations. Int J Paediatr Dent 20:305-312
48. Sato N, Ohyama K, Fukami M, Okada M, Ogata T 2006 Kallmann syndrome: somatic and germline mutations of the fibroblast growth factor receptor 1 gene in a mother and the son. J Clin Endocrinol Metab 91:1415-1418
49. Quinton R, Duke VM, Robertson A, Kirk JM, Matfin G, de Zoysa PA, Azcona C, MacColl GS, Jacobs HS, Conway GS, Besser M, Stanhope RG, Bouloux PM 2001 Idiopathic gonadotrophin deficiency: genetic questions addressed through phenotypic characterization. Clin Endocrinol (Oxf) 55:163-174 (Pubitemid 32868580)
50. Koenigkam-Santos M, Santos AC, Versiani BR, Diniz PR, Junior JE, de Castro M 2011 Quantitative magnetic resonance imaging evaluation of the olfactory system in Kallmann syndrome: correlation with a clinical smell test. Neuroendocrinology 94:209-217
51. Trarbach EB, Abreu AP, Silveira LF, Garmes HM, Baptista MT, Teles MG, Costa EM, Mohammadi M, Pitteloud N, Mendonca BB, Latronico AC 2010 Nonsense mutations in FGF8 gene causing different degrees of human gonadotropin-releasing deficiency. J Clin Endocrinol Metab 95:3491-3496
52. Kim HG, Kurth I, Lan F, Meliciani I, Wenzel W, Eom SH, Kang GB, Rosenberger G, Tekin M, Ozata M, Bick DP, Sherins RJ, Walker SL, Shi Y, Gusella JF, Layman LC 2008 Mutations in CHD7, encoding a chromatin-remodeling protein, cause idiopathic hypogonadotropic hypogonadism and Kallmann syndrome. Am J Hum Genet 83:511-519
53. Jongmans MC, van Ravenswaaij-Arts CM, Pitteloud N, Ogata T, Sato N, Claahsen-van der Grinten HL, van der Donk K, Seminara S, Bergman JE, Brunner HG, Crowley Jr WF, Hoefsloot LH 2009 CHD7 mutations in patients initially diagnosed with Kallmann syndrome-the clinical overlap with CHARGE syndrome. Clin Genet 75:65-71
54. Kim HG, Ahn JW, Kurth I, Ullmann R, Kim HT, Kulharya A, Ha KS, Itokawa Y, Meliciani I, Wenzel W, Lee D, Rosenberger G, Ozata M, Bick DP, Sherins RJ, Nagase T, Tekin M, Kim SH, Kim CH, Ropers HH, Gusella JF, Kalscheuer V, Choi CY, Layman LC 2010 WDR11, a WD protein that interacts with transcription factor EMX1, is mutated in idiopathic hypogonadotropic hypogonadism and Kallmann syndrome. Am J Hum Genet 87:465-479
55. Nimri R, Lebenthal Y, Lazar L, Chevrier L, Phillip M, Bar M, Hernandez-Mora E, de Roux N, Gat-Yablonski G 2011 A novel loss-of-function mutation in GPR54/KISS1R leads to hypogonadotropic hypogonadism in a highly consanguineous family. J Clin Endocrinol Metab 96:E536-E545
56. Topaloglu AK, Reimann F, Guclu M, Yalin AS, Kotan LD, Porter KM, Serin A, Mungan NO, Cook JR, Ozbek MN, Imamoglu S, Akalin NS, Yuksel B, O'Rahilly S, Semple RK 2009 TAC3 and TACR3 mutations in familial hypogonadotropic hypogonadism reveal a key role for neurokinin B in the central control of reproduction. Nat Genet 41:354-358
57. Young J, Bouligand J, Francou B, Raffin-Sanson ML, Gaillez S, Jeanpierre M, Grynberg M, Kamenicky P, Chanson P, Brailly-Tabard S, Guiochon-Mantel A 2010 TAC3 and TACR3 defects cause hypothalamic congenital hypogonadotropic hypogonadism in humans. J Clin Endocrinol Metab 95:2287-2295
58. Francou B, Bouligand J, Voican A, Amazit L, Trabado S, Fagart J, Meduri G, Brailly-Tabard S, Chanson P, Lecomte P, Guiochon-Mantel A, Young J 2011 Normosmic congenital hypogonadotropic hypogonadism due to TAC3/TACR3 mutations: characterization of neuroendocrine phenotypes and novel mutations. PLoS ONE 6:e25614
59. Xu N, Qin Y, Reindollar RH, Tho SP, McDonough PG, Layman LC 2007 A mutation in the fibroblast growth factor receptor 1 gene causes fully penetrant normosmic isolated hypogonadotropic hypogonadism. J Clin Endocrinol Metab 92:1155-1158 (Pubitemid 46465695)
60. Richmond EJ, Rogol AD 2007 Male pubertal development and the role of androgen therapy. Nat Clin Pract Endocrinol Metab 3:338-344 (Pubitemid 46474646)
61. Bhasin S, Cunningham GR, Hayes FJ, Matsumoto AM, Snyder PJ, Swerdloff RS, Montori VM 2006 Testosterone therapy in adult men with androgen deficiency syndromes: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab [Erratum (2006) 91: 2688] 91:1995-2010
62. Delemarre EM, Felius B, Delemarre-van de Waal HA 2008 Inducing puberty. Eur J Endocrinol 159(Suppl 1):S9-S15
63. Delemarre-van de Waal HA 2004 Application of gonadotropin releasing hormone in hypogonadotropic hypogonadism-diagnostic and therapeutic aspects. Eur J Endocrinol 151(Suppl 3):U89-U94
64. Matsumoto AM 1994 Hormonal therapy of male hypogonadism. Endocrinol Metab Clin North Am 23:857-875
65. Zitzmann M, Nieschlag E 2000 Hormone substitution in male hypogonadism. Mol Cell Endocrinol 161:73-88 (Pubitemid 30201654)
66. Drobac S, Rubin K, Rogol AD, Rosenfield RL 2006 A workshop on pubertal hormone replacement options in the United States. J Pediatr Endocrinol Metab 19:55-64 (Pubitemid 43257421)
67. Rogol AD 2005 New facets of androgen replacement therapy during childhood and adolescence. Expert Opin Pharmacother 6:1319-1336 (Pubitemid 41030892)
68. Bouvattier C, Tauber M,Jouret B, Chaussain JL, Rochiccioli P 1999 Gonadotropin treatment of hypogonadotropic hypogonadal adolescents. J Pediatr Endocrinol Metab 12:339-344 (Pubitemid 29287994)
69. Schaison G, Young J, Pholsena M, Nahoul K, Couzinet B 1993 Failure of combined follicle-stimulating hormone-testosterone administration to initiate and/or maintain spermatogenesis in men with hypogonadotropic hypogonadism. J Clin Endocrinol Metab [Erratum (1994) 78:846] 77:1545-1549
70. Quinton R, Cheow HK, Tymms DJ, Bouloux PM, Wu FC, Jacobs HS1999 Kallmann's syndrome: is it always for life? Clin Endocrinol (Oxf) 50:481-485 (Pubitemid 29193231)
71. Raivio T, Falardeau J, Dwyer A, Quinton R, Hayes FJ, Hughes VA, Cole LW, Pearce SH, Lee H, Boepple P, Crowley Jr WF, Pitteloud N 2007 Reversal of idiopathic hypogonadotropic hypogonadism. N Engl J Med 357:863-873 (Pubitemid 47347320)
72. Sykiotis GP, Plummer L, Hughes VA, Au M, Durrani S, Nayak- Young S, Dwyer AA, Quinton R, Hall JE, Gusella JF, Seminara SB, Crowley Jr WF, Pitteloud N 2010 Oligogenic basis of isolated gonadotropin- releasing hormone deficiency. Proc Natl Acad Sci USA 107:15140-15144
73. Cunningham GR, Toma SM 2011 Clinical review: why is androgen replacement in males controversial? J Clin Endocrinol Metab 96: 38-52
74. Bouvattier C, Maione L, Bouligand J, Dodé C, Guiochon-Mantel A, and Young J 18 October 2011 Neonatal gonadotropin therapy in male congenital hypogonadotropic hypogonadism. Nat Rev Endocrinol doi: 10.1038/nrendo.2011.164
75. Raivio T, Wikström AM, Dunkel L 2007 Treatment of gonadotropin- deficient boys with recombinant human FSH: long-term observation and outcome. Eur J Endocrinol 156:105-111 (Pubitemid 46553909)
76. Main KM, Schmidt IM, Toppari J, Skakkebaek NE 2002 Early postnatal treatment of hypogonadotropic hypogonadism with recombinant human FSH and LH. Eur J Endocrinol 146:75-79 (Pubitemid 34126422)
77. Main KM, Schmidt IM, Skakkebaek NE 2000 A possible role for reproductive hormones in newborn boys: progressive hypogonadism without the postnatal testosterone peak. J Clin Endocrinol Metab 85:4905-4907 (Pubitemid 32157684)
78. Bougnères P, François M, Pantalone L, Rodrigue D, Bouvattier C, Demesteere E, Roger D, Lahlou N 2008 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 93:2202-2205 (Pubitemid 351831536)
79. Leifke E, Körner HC, Link TM, Behre HM, Peters PE, Nieschlag E 1998 Effects of testosterone replacement therapy on cortical and trabecular bone mineral density, vertebral body area and paraspinal muscle area in hypogonadal men. Eur J Endocrinol 138:51-58 (Pubitemid 28078809)