{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T19:20:21Z","timestamp":1791832821258,"version":"4.3.4"},"reference-count":34,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2016,1,18]],"date-time":"2016-01-18T00:00:00Z","timestamp":1453075200000},"content-version":"vor","delay-in-days":17,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Andrology"],"published-print":{"date-parts":[[2016,1]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Germ cell and Sertoli cell proliferation and maturation in human testes occur in three main waves, during the late fetal and early neonatal period and at early puberty. They are triggered by periods of increased activity of the hypothalamic\u2010pituitary\u2010gonadal (<jats:styled-content style=\"fixed-case\">HPG<\/jats:styled-content>) axis. In hypogonadotropic hypogonadism (<jats:styled-content style=\"fixed-case\">HH<\/jats:styled-content>), these processes are variably disturbed. The objective of this study was to explore whether success of gonadotropin replacement in <jats:styled-content style=\"fixed-case\">HH<\/jats:styled-content> men is predictable by the origin of <jats:styled-content style=\"fixed-case\">HH<\/jats:styled-content>, indicating time of onset and severity of Gn<jats:styled-content style=\"fixed-case\">RH<\/jats:styled-content>\/gonadotropin deficiency. The data of 51 adult <jats:styled-content style=\"fixed-case\">HH<\/jats:styled-content> patients who had undergone one cycle of <jats:styled-content style=\"fixed-case\">hCG<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">FSH<\/jats:styled-content> treatment were reviewed. Five groups were established, according to the underlying <jats:styled-content style=\"fixed-case\">HH<\/jats:styled-content> origin. Therapeutic success by final bi\u2010testicular volumes (<jats:styled-content style=\"fixed-case\">BTV<\/jats:styled-content>s) final sperm concentrations (<jats:styled-content style=\"fixed-case\">SC<\/jats:styled-content>) and conception rates were compared and related to baseline parameters, indicative of the degree of <jats:styled-content style=\"fixed-case\">HPG<\/jats:styled-content>\u2010axis disruption. Overall, <jats:styled-content style=\"fixed-case\">BTV<\/jats:styled-content>s rose from 13\u00a0\u00b1\u00a015 to 27\u00a0\u00b1\u00a015\u00a0mL, spermatogenesis was induced in 98%, with mean <jats:styled-content style=\"fixed-case\">SC<\/jats:styled-content>s of 15\u00a0\u00b1\u00a030\u00a0mill\/mL, spontaneous pregnancies in 37% and additional 18% via intracytoplasmic sperm injection. Kallmann syndrome patients had the poorest responses (<jats:styled-content style=\"fixed-case\">BTV<\/jats:styled-content>: 16.9\u00a0\u00b1\u00a010\u00a0mL; <jats:styled-content style=\"fixed-case\">SC<\/jats:styled-content>: 3.5\u00a0\u00b1\u00a05.6\u00a0mill\/mL), followed by patients with congenital\/infancy\u2010acquired multiple pituitary hormone deficiencies (<jats:styled-content style=\"fixed-case\">MPHD<\/jats:styled-content>) and patients with <jats:styled-content style=\"fixed-case\">HH<\/jats:styled-content>+absent puberty (<jats:styled-content style=\"fixed-case\">BTV<\/jats:styled-content>: 21\u00a0\u00b1\u00a014\/24\u00a0\u00b1\u00a09\u00a0mL; <jats:styled-content style=\"fixed-case\">SC<\/jats:styled-content>: 5.5\u00a0\u00b1\u00a06.5\/ 14.5\u00a0\u00b1\u00a023.8\u00a0mill\/mL). <jats:styled-content style=\"fixed-case\">HH<\/jats:styled-content> men with pubertal arrest and with post\u2010pubertally acquired <jats:styled-content style=\"fixed-case\">MPHD<\/jats:styled-content> had the best results (<jats:styled-content style=\"fixed-case\">BTV<\/jats:styled-content>: 36\u00a0\u00b1\u00a014\/38\u00a0\u00b1\u00a016\u00a0mL; <jats:styled-content style=\"fixed-case\">SC<\/jats:styled-content>: 25.4\u00a0\u00b1\u00a034.2\/29.9\u00a0\u00b1\u00a050.5\u00a0mill\/mL). Earlier conception after 20.3\u00a0\u00b1\u00a011.5\u00a0months (vs. 43.1\u00a0\u00b1\u00a043.8; <jats:italic>p\u00a0<\/jats:italic>=\u00a00.047) of gonadotropin treatment with higher pregnancy rates (62% vs. 42%) was achieved in the two post\u2010pubertally acquired <jats:styled-content style=\"fixed-case\">HH<\/jats:styled-content> subgroups, compared to the three pre\u2010pubertally acquired. Therapeutic success was higher in patients without previously undescended testes, with higher baseline <jats:styled-content style=\"fixed-case\">BTV<\/jats:styled-content>s (pre\u2010 vs. post\u2010pubertal <jats:styled-content style=\"fixed-case\">HH<\/jats:styled-content>: 5\u00a0\u00b1\u00a04\u00a0mL vs. 26\u00a0\u00b1\u00a016\u00a0mL; <jats:italic>p\u00a0<\/jats:italic>&lt;<jats:italic>\u00a0<\/jats:italic>0.0001) and higher baseline inhibinB levels (pre\u2010 vs. post\u2010pubertal <jats:styled-content style=\"fixed-case\">HH<\/jats:styled-content>: 16.6 vs. 144.5\u00a0pg\/mL; <jats:italic>p\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>0.0004). The cause of <jats:styled-content style=\"fixed-case\">HH<\/jats:styled-content> is a valuable predictor of outcome of gonadotropin replacement in adults.<\/jats:p>","DOI":"10.1111\/andr.12128","type":"journal-article","created":{"date-parts":[[2016,1,18]],"date-time":"2016-01-18T20:01:34Z","timestamp":1453147294000},"page":"87-94","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":68,"title":["Causes of hypogonadotropic hypogonadism predict response to gonadotropin substitution in adults"],"prefix":"10.1111","volume":"4","author":[{"given":"J.","family":"Rohayem","sequence":"first","affiliation":[{"name":"Centre of Reproductive Medicine and Andrology Department of Clinical Andrology University of Muenster  Muenster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Sinthofen","sequence":"additional","affiliation":[{"name":"Centre of Reproductive Medicine and Andrology Department of Clinical Andrology University of Muenster  Muenster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Nieschlag","sequence":"additional","affiliation":[{"name":"Centre of Reproductive Medicine and Andrology Department of Clinical Andrology University of Muenster  Muenster Germany"},{"name":"Center of Excellence in Genomic Medicine Research King Abdulaziz University  Jeddah Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Kliesch","sequence":"additional","affiliation":[{"name":"Centre of Reproductive Medicine and Andrology Department of Clinical Andrology University of Muenster  Muenster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Zitzmann","sequence":"additional","affiliation":[{"name":"Centre of Reproductive Medicine and Andrology Department of Clinical Andrology University of Muenster  Muenster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,1,18]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF03345541"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2605.1989.tb01328.x"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1530\/eje.0.1390298"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-66-6-1144"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2012-4116"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2009.12.012"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1122"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.0020175"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2013-2518"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI34538"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/353529a0"},{"key":"e_1_2_10_13_1","first-page":"179","article-title":"Impuberism and hypogonadism at induction into military service. 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