{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T19:13:53Z","timestamp":1780514033614,"version":"3.54.1"},"reference-count":38,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2022,10,17]],"date-time":"2022-10-17T00:00:00Z","timestamp":1665964800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81100578"],"award-info":[{"award-number":["81100578"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Endocrinology"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>A direct evaluation of insulin sensitivity on pituitary response to gonadotropin relasing hormone (GnRH) has not been shown in congenital hypogonadotropic hypogonadism (CHH), despite a growing body of evidence in the association of testosterone concentrations with insulin sensitiviy. The objective of the study was to explore whether increased testosterone concentrations in men with CHH improve insulin sensitivity, or vice versa.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>A retrospective study at a tertiary centre.<\/jats:p><\/jats:sec><jats:sec><jats:title>Patients<\/jats:title><jats:p>Series of male CHH patients were included from Jannuary 2014 to December 2019.<\/jats:p><\/jats:sec><jats:sec><jats:title>Measurements<\/jats:title><jats:p>Insulin sensitivity indices calculated from oral glucose tolerance test and steroid hormone levels were examined in 52 patients with newly diagnosed CHH and 22 healthy controls. Thirty\u2010two of the 52 CHH patients received pulsatile GnRH therapy with follow\u2010up every 3\u20136 months.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared to healthy controls, CHH patients had elevated 2\u2009h\u00a0post\u2010load glucose, HbA1c, fasting insulin, HOMA of insulin resistance\u00a0(HOMA\u2010IR)\u00a0and decreased Matsuda index and testosterone (<jats:italic>p<\/jats:italic>\u2009\u2264\u2009.01). The median follow\u2010up for patients (<jats:italic>n<\/jats:italic>\u2009=\u200932) who received pulsatile GnRH therapy was 13.5 (11.3\u221224) months (432 person\u2010months in total). GnRH therapy increased testosterone and Matsuda index (<jats:italic>p<\/jats:italic>\u2009\u2264\u2009.0001), whilst decreased platelet count (<jats:italic>p<\/jats:italic>\u2009=\u2009.04), leptin (<jats:italic>p<\/jats:italic>\u2009=\u2009.04), fasting glucose (<jats:italic>p<\/jats:italic>\u2009=\u2009.01)\u00a0and HOMA\u2010IR (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.0001) compared with baseline. The median treatment duration first time to reach the lower limit of normal testosterone concentrations of patients with high and low baseline insulin sensitivity was 15 (95% CI:\u00a08.1\u221221.9) and 30 months (21.2\u221238.8), respectively. Correspondingly, after GnRH therapy, luteinizing hormone responsiveness to GnRH provocative test was more vigorous in patients with high insulin sensitivity than those with low insulin sensitivity [17.0 (9.5\u221225.9)\u00a0vs. 8.2 (3.3\u221213.0), <jats:italic>p<\/jats:italic>\u2009=\u2009.01].<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Pulsatile GnRH therapy elevated testosterone levels in male CHH patients, ameliorated impaired insulin sensitivity and attenuated subclinical inflammatory response, increased insulin sensitivity, in turn, may benefit the efficacy of pulsatile GnRH therapy.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cen.14829","type":"journal-article","created":{"date-parts":[[2022,10,1]],"date-time":"2022-10-01T04:59:03Z","timestamp":1664600343000},"page":"783-791","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Changes in levels of testosterone, insulin sensitivity and metabolic profiles during GnRH therapy: Reciprocity between insulin sensitivity and pituitary responsiveness to GnRH in teenage and young male patients with congenital hypogonadotropic hypogonadism"],"prefix":"10.1111","volume":"97","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6429-2581","authenticated-orcid":false,"given":"Hong\u2010Qi","family":"Fan","sequence":"first","affiliation":[{"name":"Department of Endocrinology The First Affiliated Hospital of Nanjing Medical University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu\u2010Cheng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology The First Affiliated Hospital of Nanjing Medical University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"He","sequence":"additional","affiliation":[{"name":"Department of Endocrinology The First Affiliated Hospital of Nanjing Medical University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong\u2010Wen","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Endocrinology The First Affiliated Hospital of Nanjing Medical University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6375-3622","authenticated-orcid":false,"given":"Tao","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology The First Affiliated Hospital of Nanjing Medical University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,10,17]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00592-018-1163-6"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2015.12.005"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.54.6.1717"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.295.11.1288"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/andr.12568"},{"key":"e_1_2_7_7_1","first-page":"33","article-title":"Testosterone, dihydrotestosterone, sex hormone\u2010binding globulin, and incident diabetes among older men: the cardiovascular health study","volume":"102","author":"Joyce KE","year":"2017","journal-title":"J Clin Endocrinol Metab"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.48.10.2039"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.50.11.2444"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.87.1.8172"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1530\/eje.0.1480055"},{"key":"e_1_2_7_12_1","first-page":"991","article-title":"The effects of testosterone treatment on body composition and metabolism in middle\u2010aged obese men","volume":"16","author":"M\u00e5rin P","year":"1992","journal-title":"Int J Obes Relat Metab Disord"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1550-8528.1993.tb00618.x"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2265.2010.03939.x"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1210\/er.2018-00116"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc17-2510"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1586\/eem.09.65"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2015-1343"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deaa185"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-150-9-200905050-00006"},{"key":"e_1_2_7_21_1","first-page":"836","article-title":"The application of gonadotropin in treatment of male central hypogonadism","volume":"44","author":"Di FS","year":"2005","journal-title":"Zhonghua Nei Ke Za Zhi"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.22.9.1462"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.85.12.4426"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2007.11.044"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc15-1518"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(20)30367-3"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1159\/000443283"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/cen.14673"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc08-0369"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI29069"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2005-0780"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2002-020516"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1089\/met.2018.0016"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0026-0495(03)00099-4"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2004-2190"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo-119-4-1641"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.451773"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers7040883"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0015-0282(02)04346-7"}],"container-title":["Clinical Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cen.14829","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cen.14829","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cen.14829","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,22]],"date-time":"2023-08-22T06:51:10Z","timestamp":1692687070000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cen.14829"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,17]]},"references-count":38,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2022,12]]}},"alternative-id":["10.1111\/cen.14829"],"URL":"https:\/\/doi.org\/10.1111\/cen.14829","archive":["Portico"],"relation":{},"ISSN":["0300-0664","1365-2265"],"issn-type":[{"value":"0300-0664","type":"print"},{"value":"1365-2265","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,17]]},"assertion":[{"value":"2022-07-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-09-27","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-10-17","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}