{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T16:16:23Z","timestamp":1761581783768,"version":"3.40.5"},"reference-count":28,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2019,1,4]],"date-time":"2019-01-04T00:00:00Z","timestamp":1546560000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Andrology"],"published-print":{"date-parts":[[2019,7]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Primary hypogonadism (low testosterone and high luteinizing hormone, <jats:styled-content style=\"fixed-case\">LH<\/jats:styled-content>) is present in approximately 20% of testicular cancer (<jats:styled-content style=\"fixed-case\">TC<\/jats:styled-content>) survivors after orchidectomy with or without chemotherapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>We investigated insulin\u2010like factor\u00a03 (<jats:styled-content style=\"fixed-case\">INSL<\/jats:styled-content>3), a novel marker of Leydig cell function, in <jats:styled-content style=\"fixed-case\">TC<\/jats:styled-content> patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>We analyzed: (I) a cross\u2010sectional cohort of <jats:styled-content style=\"fixed-case\">TC<\/jats:styled-content> patients after orchidectomy with or without chemotherapy (1988\u20131999) at long\u2010term follow\u2010up (median 36 and 35\u00a0years of age at follow\u2010up, respectively) and healthy men of similar age; (<jats:styled-content style=\"fixed-case\">II<\/jats:styled-content>) a longitudinal cohort of chemotherapy\u2010treated <jats:styled-content style=\"fixed-case\">TC<\/jats:styled-content> patients (2000\u20132008), analyzed before and 1\u00a0year after chemotherapy (median 29\u00a0years of age at chemotherapy). <jats:styled-content style=\"fixed-case\">INSL<\/jats:styled-content>3, testosterone, and <jats:styled-content style=\"fixed-case\">LH<\/jats:styled-content> were compared between groups and over time and related to pre\u2010chemotherapy \u03b2\u2010<jats:styled-content style=\"fixed-case\">hCG<\/jats:styled-content> levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In the cross\u2010sectional cohort, <jats:styled-content style=\"fixed-case\">TC<\/jats:styled-content> patients at median 7\u00a0years after orchidectomy and chemotherapy (<jats:italic>n\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>79) had higher <jats:styled-content style=\"fixed-case\">LH<\/jats:styled-content> (<jats:italic>p\u00a0<\/jats:italic>&lt;\u00a00.001), lower testosterone (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.001), but similar <jats:styled-content style=\"fixed-case\">INSL<\/jats:styled-content>3 as controls (<jats:italic>n<\/jats:italic>\u00a0=\u00a040). After orchidectomy only (<jats:italic>n\u00a0=\u00a0<\/jats:italic>25), higher <jats:styled-content style=\"fixed-case\">LH<\/jats:styled-content> (<jats:italic>p\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>0.02), but no differences in testosterone or <jats:styled-content style=\"fixed-case\">INSL<\/jats:styled-content>3 were observed compared to controls. In the longitudinal cohort, patients with normal pre\u2010chemotherapy \u03b2\u2010<jats:styled-content style=\"fixed-case\">hCG<\/jats:styled-content> (\u22645\u00a0<jats:styled-content style=\"fixed-case\">mU<\/jats:styled-content>\/L, <jats:italic>n\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>35) had increased <jats:styled-content style=\"fixed-case\">LH<\/jats:styled-content> 1\u00a0year after chemotherapy compared to pre\u2010chemotherapy (<jats:italic>p\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>0.001), and no change in testosterone or <jats:styled-content style=\"fixed-case\">INSL<\/jats:styled-content>3. In contrast, patients with high \u03b2\u2010<jats:styled-content style=\"fixed-case\">hCG<\/jats:styled-content> pre\u2010chemotherapy (<jats:italic>n\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>42) had suppressed <jats:styled-content style=\"fixed-case\">LH<\/jats:styled-content>, markedly elevated testosterone, and low <jats:styled-content style=\"fixed-case\">INSL<\/jats:styled-content>3 at start of chemotherapy, with increased <jats:styled-content style=\"fixed-case\">LH<\/jats:styled-content>, decreased testosterone, and increased <jats:styled-content style=\"fixed-case\">INSL<\/jats:styled-content>3 1\u00a0year later (all <jats:italic>p\u00a0<\/jats:italic>&lt;<jats:italic>\u00a0<\/jats:italic>0.001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Changes in <jats:styled-content style=\"fixed-case\">LH<\/jats:styled-content> show that gonadal endocrine function is disturbed before chemotherapy, 1\u00a0year later, and at long\u2010term follow\u2010up in chemotherapy\u2010treated <jats:styled-content style=\"fixed-case\">TC<\/jats:styled-content> patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Pre\u2010chemotherapy, \u03b2\u2010<jats:styled-content style=\"fixed-case\">hCG<\/jats:styled-content>\u2010producing tumors affect the gonadal endocrine axis, demonstrated by increased testosterone and decreased <jats:styled-content style=\"fixed-case\">LH<\/jats:styled-content>. <jats:styled-content style=\"fixed-case\">INSL<\/jats:styled-content>3 did not uniformly follow the pattern of testosterone.<\/jats:p><\/jats:sec>","DOI":"10.1111\/andr.12581","type":"journal-article","created":{"date-parts":[[2019,1,4]],"date-time":"2019-01-04T19:06:42Z","timestamp":1546628802000},"page":"441-448","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Insulin\u2010like factor 3, luteinizing hormone and testosterone in testicular cancer patients: effects of \u03b2\u2010<scp>hCG<\/scp> and cancer treatment"],"prefix":"10.1111","volume":"7","author":[{"given":"L. C.","family":"Steggink","sequence":"first","affiliation":[{"name":"Department of Medical Oncology University of Groningen University Medical Center Groningen Groningen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. P.","family":"van Beek","sequence":"additional","affiliation":[{"name":"Division of Endocrinology Department of Internal Medicine University of Groningen University Medical Center Groningen Groningen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H.","family":"Boer","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology University of Groningen University Medical Center Groningen Groningen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C.","family":"Meijer","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology University of Groningen University Medical Center Groningen Groningen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Lubberts","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology University of Groningen University Medical Center Groningen Groningen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S. F.","family":"Oosting","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology University of Groningen University Medical Center Groningen Groningen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"I. J.","family":"de Jong","sequence":"additional","affiliation":[{"name":"Department of Urology University of Groningen University Medical Center Groningen Groningen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R. J.","family":"van Ginkel","sequence":"additional","affiliation":[{"name":"Division of Surgical Oncology Department of Surgery University of Groningen University Medical Center Groningen Groningen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. D.","family":"Lefrandt","sequence":"additional","affiliation":[{"name":"Division of Vascular Medicine Department of Internal Medicine University of Groningen University Medical Center Groningen Groningen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. 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