{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T08:36:58Z","timestamp":1791275818144,"version":"4.1.0"},"reference-count":23,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2015,9,7]],"date-time":"2015-09-07T00:00:00Z","timestamp":1441584000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bjui-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BJU International"],"published-print":{"date-parts":[[2016,2]]},"abstract":"\n Objectives<\/jats:title>\n \n To determine, in a chronic dosing study, the oral toxicity potential of the test substances, enclomiphene citrate (\n ENC<\/jats:styled-content>\n ) and zuclomiphene citrate (\n ZUC<\/jats:styled-content>\n ), when administered to male mice by oral gavage.\n <\/jats:p>\n <\/jats:sec>\n \n Materials and Methods<\/jats:title>\n \n Mice were divided into five treatment groups. Group\n I<\/jats:styled-content>\n , placebo; Group\n II<\/jats:styled-content>\n , 40\u00a0mg\/kg body weight\/day\n ENC<\/jats:styled-content>\n ; Group\n III<\/jats:styled-content>\n , 4\u00a0mg\/kg\/day\n ENC<\/jats:styled-content>\n ; Group\n IV<\/jats:styled-content>\n , 40\u00a0mg\/kg\/day\n ZUC<\/jats:styled-content>\n ; Group\n V<\/jats:styled-content>\n , 4\u00a0mg\/kg\/day\n ZUC<\/jats:styled-content>\n . Serum samples and tissues were obtained from each mouse for analysis and body weights were measured.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n In this chronic dosing study in mice, profound effects on\n L<\/jats:styled-content>\n eydig cells, epididymis, seminal vesicles, and kidneys were\u00a0seen, as well as effects on serum testosterone, follicle\u2010stimulating hormone and luteinising hormone levels that were associated with\n ZUC<\/jats:styled-content>\n treatment only. Treatment with the isolated enclomiphene isomer had positive effects on testosterone production and no effects on testicular histology.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n The present study suggests that an unopposed high dose of zuclomiphene can have pernicious effects on male mammalian reproductive organs. The deleterious effects seen when administering\n ZUC<\/jats:styled-content>\n in male mice, justifies the case for a monoisomeric preparation and the development of\n ENC<\/jats:styled-content>\n for clinical use in human males to increase serum levels of testosterone and maintain sperm counts.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/bju.13244","type":"journal-article","created":{"date-parts":[[2015,7,28]],"date-time":"2015-07-28T01:13:43Z","timestamp":1438046023000},"page":"344-350","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Differential effects of isomers of clomiphene citrate on reproductive tissues in male mice"],"prefix":"10.1111","volume":"117","author":[{"given":"Gregory K.","family":"Fontenot","sequence":"first","affiliation":[{"name":"Repros Therapeutics Inc. The Woodlands TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald D.","family":"Wiehle","sequence":"additional","affiliation":[{"name":"Repros Therapeutics Inc. The Woodlands TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph S.","family":"Podolski","sequence":"additional","affiliation":[{"name":"Repros Therapeutics Inc. 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