{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T03:08:56Z","timestamp":1780628936495,"version":"3.54.1"},"reference-count":41,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2019,11,18]],"date-time":"2019-11-18T00:00:00Z","timestamp":1574035200000},"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":["Clinical Endocrinology"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Clomiphene citrate (CC) has been shown to restore the hypothalamic\u2010pituitary\u2010gonadal (HPG) axis by increasing testosterone (T) levels to physiological levels in patients with dysmetabolic conditions such as obesity, metabolic syndrome and type 2 diabetes mellitus (T2DM). However, the data are unclear regarding the effects on Sertoli cell (SC) function.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>To study SC function by assessing Inhibin B (IB) and anti\u2010Mullerian hormone (AMH) levels at baseline and after 3\u00a0months of CC treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and methods<\/jats:title><jats:p>This is an ancillary study of a cross\u2010over, randomised, double\u2010blind, placebo\u2010controlled trial performed to evaluate androgen response to CC treatment in dysmetabolic obese subjects with low T levels treated with metformin. We evaluated SC function by assessing IB and AMH levels at baseline and after 3\u00a0months of each treatment in ten dysmetabolic obese subjects with low T levels. In all subjects, the influence of the clinical characteristics, metabolic and hormonal baseline parameters on SC and Leydig (LC) function, evaluated respectively with AMH, IB, follicle\u2010stimulating hormone (FSH) and T levels, was tested.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>No significant changes were observed for IB and AMH concentrations after each treatment period. Whereas T and oestradiol (E2) levels were shown to be significantly higher in the CC plus metformin phase (CC\/Met) only. No clinical, metabolic or hormonal parameters showed significant effects on serum AMH at baseline or after treatments. However, baseline T, dihydrotestosterone (DHT) and E2 positively affected IB levels during CC\/Met therapy (<jats:italic>P<\/jats:italic>\u00a0=\u00a0.003, <jats:italic>P<\/jats:italic>\u00a0=\u00a0.038 and <jats:italic>P<\/jats:italic>\u00a0=\u00a0.049, respectively). Baseline leptin and FSH had a negative (<jats:italic>P<\/jats:italic>\u00a0=\u00a0031) and positive (<jats:italic>P<\/jats:italic>\u00a0=\u00a0.048) respectively role on T levels during CC\/Met, as they were statistically significant compared to the placebo period (Plac\/Met).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Unlike the LC activity, CC was unable to influence SC function, as shown by the lack of IB and AMH serum modifications, thus suggesting an intrinsic nonreversible defect of SC cells in patients with dysmetabolic conditions.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cen.14122","type":"journal-article","created":{"date-parts":[[2019,11,2]],"date-time":"2019-11-02T03:43:35Z","timestamp":1572666215000},"page":"38-45","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Effect of clomiphene citrate treatment on the Sertoli cells of dysmetabolic obese men with low testosterone levels"],"prefix":"10.1111","volume":"92","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6390-2146","authenticated-orcid":false,"given":"Carla","family":"Pelusi","sequence":"first","affiliation":[{"name":"Endocrinology Unit and Center for Applied Biomedical Research Department of Medical &amp; Surgical Sciences (DIMEC) Alma Mater Studiorum University of Bologna S. Orsola\u2010Malpighi Hospital Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flaminia","family":"Fanelli","sequence":"additional","affiliation":[{"name":"Endocrinology Unit and Center for Applied Biomedical Research Department of Medical &amp; Surgical Sciences (DIMEC) Alma Mater Studiorum University of Bologna S. Orsola\u2010Malpighi Hospital Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margherita","family":"Baccini","sequence":"additional","affiliation":[{"name":"Endocrinology Unit and Center for Applied Biomedical Research Department of Medical &amp; Surgical Sciences (DIMEC) Alma Mater Studiorum University of Bologna S. Orsola\u2010Malpighi Hospital Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Triggiani","sequence":"additional","affiliation":[{"name":"Interdisciplinary Department of Medicine Internal Medicine Geriatrics, Endocrinology and Rare Diseases University of Bari Bari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8540-4615","authenticated-orcid":false,"given":"Nicola","family":"Bartolomeo","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science and Human Oncology University of Bari Bari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo Domenico","family":"Carbone","sequence":"additional","affiliation":[{"name":"Institute of Clinical and Hormonal Research Foggia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"De Pergola","sequence":"additional","affiliation":[{"name":"Nutrition Outpatient Clinic Clinical Oncology Unit University of Bari Bari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guido","family":"Di Dalmazi","sequence":"additional","affiliation":[{"name":"Endocrinology Unit and Center for Applied Biomedical Research Department of Medical &amp; Surgical Sciences (DIMEC) Alma Mater Studiorum University of Bologna S. Orsola\u2010Malpighi Hospital Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uberto","family":"Pagotto","sequence":"additional","affiliation":[{"name":"Endocrinology Unit and Center for Applied Biomedical Research Department of Medical &amp; Surgical Sciences (DIMEC) Alma Mater Studiorum University of Bologna S. Orsola\u2010Malpighi Hospital Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renato","family":"Pasquali","sequence":"additional","affiliation":[{"name":"Endocrinology Unit and Center for Applied Biomedical Research Department of Medical &amp; Surgical Sciences (DIMEC) Alma Mater Studiorum University of Bologna S. Orsola\u2010Malpighi Hospital Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vito Angelo","family":"Giagulli","sequence":"additional","affiliation":[{"name":"Outpatients Clinic of Endocrinology and Metabolic Disease Conversano Hospital Bari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,11,18]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2009-1796"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-66-1-62"},{"key":"e_1_2_9_4_1","first-page":"689","article-title":"Could androgen receptor gene CAG tract polymorphism affect spermatogenesis in men with idiopathic infertility?","volume":"31","author":"Giagulli VA","year":"2014","journal-title":"J Assist Reprod Genet"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF03349232"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2016-3580"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2018-00229"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc17-2510"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-12-0955"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0183369"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/jsm.12944"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/andr.12232"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.4103\/1008-682X.175783"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/bju.14558"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-08-0601"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2007-0117"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ijir.3900857"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1210\/js.2018-00414"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.steroids.2010.11.005"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2013-1381"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.4780081202"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/jsm.12549"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.4103\/aja.aja_44_18"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2017-00196"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/andr.12459"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrurol.2012.77"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/andr.12107"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.numecd.2004.09.002"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1439-0272.2011.01185.x"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2003.09.020"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2004-0542"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF03344180"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2019.00224"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.2164\/jandrol.05193"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1507\/endocrj.52.345"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2015-1571"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-013-1722-7"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmp047"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0100409"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.84.10.3673"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0039-128X(99)00041-0"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-4731(86)90071-3"}],"container-title":["Clinical Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcen.14122","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cen.14122","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cen.14122","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cen.14122","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,3]],"date-time":"2023-09-03T09:03:25Z","timestamp":1693731805000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cen.14122"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11,18]]},"references-count":41,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,1]]}},"alternative-id":["10.1111\/cen.14122"],"URL":"https:\/\/doi.org\/10.1111\/cen.14122","archive":["Portico"],"relation":{},"ISSN":["0300-0664","1365-2265"],"issn-type":[{"value":"0300-0664","type":"print"},{"value":"1365-2265","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,11,18]]},"assertion":[{"value":"2019-06-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-10-30","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-11-18","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}