{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T02:18:27Z","timestamp":1783477107272,"version":"3.55.0"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2020,8,30]],"date-time":"2020-08-30T00:00:00Z","timestamp":1598745600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"crossref","award":["ANR-09-GENO-017-01"],"award-info":[{"award-number":["ANR-09-GENO-017-01"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"crossref"}]},{"name":"French Ministry of Health","award":["PHRC-2009 HYPO-PROTEO"],"award-info":[{"award-number":["PHRC-2009 HYPO-PROTEO"]}]},{"name":"French Ministry of Health","award":["N\u00b0P081212"],"award-info":[{"award-number":["N\u00b0P081212"]}]},{"name":"French Ministry of Health","award":["P081216\/IDRCB 2009-A00892-55"],"award-info":[{"award-number":["P081216\/IDRCB 2009-A00892-55"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>STUDY QUESTION<\/jats:title>\n                  <jats:p>Are GnRH tests and serum inhibin B levels sufficiently discriminating to distinguish transient constitutional delay of growth and puberty (CDGP) from congenital hypogonadotropic hypogonadism (CHH) that affects reproductive health for life?<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>SUMMARY ANSWER<\/jats:title>\n                  <jats:p>Both parameters lack the specificity to discriminate CDGP from CHH.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>WHAT IS KNOWN ALREADY<\/jats:title>\n                  <jats:p>GnRH tests and inhibin B levels have been proposed to differentiate CDGP from CHH. However, their diagnostic accuracies have been hampered by the small numbers of CHH included and enrichment of CHH patients with more severe forms.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>STUDY DESIGN, SIZE, DURATION<\/jats:title>\n                  <jats:p>The aim of this study was to assess the diagnostic performance of GnRH tests and inhibin B measurements in a large cohort of CHH male patients with the whole reproductive spectrum. From 2008 to 2018, 232 males were assessed: 127 with CHH, 74 with CDGP and 31 healthy controls.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>PARTICIPANTS\/MATERIALS, SETTING, METHODS<\/jats:title>\n                  <jats:p>The participants were enrolled in two French academic referral centres. The following measurements were taken: testicular volume (TV), serum testosterone, inhibin B, LH and FSH, both at baseline and following the GnRH test.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>MAIN RESULTS AND THE ROLE OF CHANCE<\/jats:title>\n                  <jats:p>Among CHH patients, the LH response to the GnRH test was very variable and correlated with TV. Among CDGP patients, the LH peak was also variable and 47% of CHH patients had peak LH levels overlapping with the CDGP group. However, no patients with CDGP had an LH peak below 4.0 IU\/l, while 53% CHH patients had LH peak below this threshold. Among CHH patients, inhibin B levels were also variable and correlated with TV and peak LH. Inhibin B was significantly lower in CHH patients than in CDGP patients but 50% of CHH values overlapped with CDGP values. Interestingly, all patients with CDGP had inhibin B levels above 35 pg\/ml but 50% of CHH patients also had levels above this threshold.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>LIMITATIONS, REASONS FOR CAUTION<\/jats:title>\n                  <jats:p>As CHH is very rare, an international study would be necessary to recruit a larger CHH cohort and consolidate the conclusion reached here.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>WIDER IMPLICATIONS OF THE FINDINGS<\/jats:title>\n                  <jats:p>Peak LH and basal inhibin B levels are variable in both CHH and CDGP with significant overlap. Both parameters lack specificity and sensitivity to efficiently discriminate CHH from CDGP. This reflects the varying degree of gonadotropin deficiency inherent to CHH. These two diagnostic procedures may misdiagnose partial forms of isolated (non-syndromic) CHH, allowing them to be erroneously considered as CDGP.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>STUDY FUNDING\/COMPETING INTEREST(S)<\/jats:title>\n                  <jats:p>This study was funded by Agence Fran\u00e7aise de Lutte contre le Dopage: Grant Hypoproteo AFLD-10 (to J.Y.); Agence Nationale de la Recherche (ANR): Grant ANR-09-GENO-017-01 (to J.Y.); European Cooperation in Science and Technology, COST Action BM1105; Programme Hospitalier de Recherche Clinique (PHRC), French Ministry of Health: PHRC-2009 HYPO-PROTEO (to J.Y.); and Programme Hospitalier de Recherche Clinique (PHRC) \u201cVari\u00e9t\u00e9\u201d, French Ministry of Health, N\u00b0 P081216\/IDRCB 2009-A00892-55 (to P.C.). There are no competing interests.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>TRIAL REGISTRATION NUMBER<\/jats:title>\n                  <jats:p>N\/A<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/humrep\/deaa185","type":"journal-article","created":{"date-parts":[[2020,7,11]],"date-time":"2020-07-11T19:08:55Z","timestamp":1594494535000},"page":"2312-2322","source":"Crossref","is-referenced-by-count":19,"title":["GnRH stimulation testing and serum inhibin B in males: insufficient specificity for discriminating between congenital hypogonadotropic hypogonadism from constitutional delay of growth and puberty"],"prefix":"10.1093","volume":"35","author":[{"given":"H\u00e9l\u00e9na","family":"Mosbah","sequence":"first","affiliation":[{"name":"Univ Paris-Saclay, Paris-Saclay Medical School, Le Kremlin-Bic\u00eatre, France"},{"name":"Assistance Publique-H\u00f4pitaux de Paris, Bic\u00eatre Hospital, Le Kremlin-Bic\u00eatre, France"},{"name":"Department of Reproductive Endocrinology, Bic\u00eatre Hospital, Le Kremlin-Bic\u00eatre, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Bouvattier","sequence":"additional","affiliation":[{"name":"Univ Paris-Saclay, Paris-Saclay Medical School, Le Kremlin-Bic\u00eatre, France"},{"name":"Assistance Publique-H\u00f4pitaux de Paris, Bic\u00eatre Hospital, Le Kremlin-Bic\u00eatre, France"},{"name":"INSERM, U1185, Le Kremlin-Bic\u00eatre, France"},{"name":"Department of Pediatric Endocrinology, Bic\u00eatre Hospital, Le Kremlin-Bic\u00eatre, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Maione","sequence":"additional","affiliation":[{"name":"Univ Paris-Saclay, Paris-Saclay Medical School, Le Kremlin-Bic\u00eatre, France"},{"name":"Assistance Publique-H\u00f4pitaux de Paris, Bic\u00eatre Hospital, Le Kremlin-Bic\u00eatre, France"},{"name":"Department of Reproductive Endocrinology, Bic\u00eatre Hospital, Le Kremlin-Bic\u00eatre, France"},{"name":"INSERM, U1185, Le Kremlin-Bic\u00eatre, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9verine","family":"Trabado","sequence":"additional","affiliation":[{"name":"Univ Paris-Saclay, Paris-Saclay Medical School, Le Kremlin-Bic\u00eatre, France"},{"name":"Assistance Publique-H\u00f4pitaux de Paris, Bic\u00eatre Hospital, Le Kremlin-Bic\u00eatre, France"},{"name":"Department of Hormonology and Molecular Genetics, Bic\u00eatre Hospital, Le Kremlin-Bic\u00eatre, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianpaolo","family":"De Filippo","sequence":"additional","affiliation":[{"name":"Univ Paris-Saclay, Paris-Saclay Medical School, Le Kremlin-Bic\u00eatre, France"},{"name":"Assistance Publique-H\u00f4pitaux de Paris, Bic\u00eatre Hospital, Le Kremlin-Bic\u00eatre, France"},{"name":"Department of Pediatric Endocrinology, Bic\u00eatre Hospital, Le Kremlin-Bic\u00eatre, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandra","family":"Cartes","sequence":"additional","affiliation":[{"name":"Assistance Publique-H\u00f4pitaux de Paris, Bic\u00eatre Hospital, Le Kremlin-Bic\u00eatre, France"},{"name":"Department of Reproductive Endocrinology, Bic\u00eatre Hospital, Le Kremlin-Bic\u00eatre, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aur\u00e9lie","family":"Donzeau","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology, University Hospital of Angers, Angers, France"},{"name":"Reference Center for Rare Pituitary Diseases (HYPO), University Hospital of Angers, Angers, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Chanson","sequence":"additional","affiliation":[{"name":"Univ Paris-Saclay, Paris-Saclay Medical School, Le Kremlin-Bic\u00eatre, France"},{"name":"Assistance Publique-H\u00f4pitaux de Paris, Bic\u00eatre Hospital, Le Kremlin-Bic\u00eatre, France"},{"name":"Department of Reproductive Endocrinology, Bic\u00eatre Hospital, Le Kremlin-Bic\u00eatre, France"},{"name":"INSERM, U1185, Le Kremlin-Bic\u00eatre, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvie","family":"Brailly-Tabard","sequence":"additional","affiliation":[{"name":"Univ Paris-Saclay, Paris-Saclay Medical School, Le Kremlin-Bic\u00eatre, France"},{"name":"Assistance Publique-H\u00f4pitaux de Paris, Bic\u00eatre Hospital, Le Kremlin-Bic\u00eatre, France"},{"name":"Department of Hormonology and Molecular Genetics, Bic\u00eatre Hospital, Le Kremlin-Bic\u00eatre, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew A","family":"Dwyer","sequence":"additional","affiliation":[{"name":"Boston College, William F. 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