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Statins are one of the most marketed drugs in the world to treat dyslipidemia, while sibutramine, a SNRI drug, is prescribed in some countries to treat obesity and is detected as an additive in many adulterated weight loss supplements marketed worldwide. Previous studies reported adverse effects of isolated exposure to these drugs on male rat reproductive parameters. In the present work, we further investigated male reproductive toxicity of these drugs, administered in isolation or combination in adult rats for a longer period of treatment. Adult male rats (90 days) were treated (gavage) for 70 days with saline and dimethyl sulfoxide (control), sibutramine (10 mg\/kg), rosuvastatin (5 mg\/kg), or rosuvastatin combined with sibutramine. Sibutramine alone or with rosuvastatin, promoted a reduction in food intake and body weight gain, weight of the epididymis, ventral prostate and seminal vesicle; as well as decreased sperm reserves and transit time through the epididymis; androgen depletion; and increased index of cytoplasmic droplet. The rosuvastatin\u2010treated group showed reduced frequency of ejaculation. Exposure to this drug alone or combined with sibutramine impaired epididymal morphology. Co\u2010exposed rats had altered epididymal morphometry, and seminal vesicle and testis weights. The rats also showed decreased fertility after natural mating and a trend toward a delay in ejaculation, suggesting a small synergistic effect of these drugs. Given the greater reproductive efficiency of rodents, the results obtained in the present study raise concern regarding possible fertility impairment in men taking statins and SNRI drugs.<\/jats:p>","DOI":"10.1002\/jat.3955","type":"journal-article","created":{"date-parts":[[2020,2,18]],"date-time":"2020-02-18T20:40:31Z","timestamp":1582058431000},"page":"947-964","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Effects of isolated or combined exposure to sibutramine and rosuvastatin on reproductive parameters of adult male rats"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9233-2413","authenticated-orcid":false,"given":"Patr\u00edcia Villela","family":"e Silva","sequence":"first","affiliation":[{"name":"Department of Morphology, Institute of Biosciences S\u00e3o Paulo State University \u2010 UNESP  Botucatu SP Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3711-811X","authenticated-orcid":false,"given":"Cibele dos Santos","family":"Borges","sequence":"additional","affiliation":[{"name":"Department of Morphology, Institute of Biosciences S\u00e3o Paulo State University \u2010 UNESP  Botucatu SP Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josiane de Lima","family":"Rosa","sequence":"additional","affiliation":[{"name":"Department of Morphology, Institute of Biosciences S\u00e3o Paulo State University \u2010 UNESP  Botucatu SP Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tain\u00e1 Louise","family":"Pacheco","sequence":"additional","affiliation":[{"name":"Department of Morphology, Institute of Biosciences S\u00e3o Paulo State University \u2010 UNESP  Botucatu SP Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thamiris Moreira","family":"Figueiredo","sequence":"additional","affiliation":[{"name":"Department of Morphology, Institute of Biosciences S\u00e3o Paulo State University \u2010 UNESP  Botucatu SP Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9437-6310","authenticated-orcid":false,"given":"Gabriel Adan Ara\u00fajo","family":"Leite","sequence":"additional","affiliation":[{"name":"Graduate Program in Cell and Structural Biology, Institute of Biology State University of Campinas \u2013 UNICAMP  Campinas SP Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina Trevizan","family":"Guerra","sequence":"additional","affiliation":[{"name":"Department of Morphology, Institute of Biosciences S\u00e3o Paulo State University \u2010 UNESP  Botucatu SP Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janete Aparecida","family":"Anselmo\u2010Franci","sequence":"additional","affiliation":[{"name":"Department of Morphology, Physiology and Basic Pathology, School of Dentistry of Ribeir\u00e3o Preto University of S\u00e3o Paulo \u2013 USP  Ribeir\u00e3o Preto SP Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary Robert","family":"Klinefelter","sequence":"additional","affiliation":[{"name":"Reproductive Toxicity Branch, Toxicity Assessment Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development US Environmental Protection Agency  North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilma De Grava","family":"Kempinas","sequence":"additional","affiliation":[{"name":"Department of Morphology, Institute of Biosciences S\u00e3o Paulo State University \u2010 UNESP  Botucatu SP Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,2,18]]},"reference":[{"issue":"11","key":"e_1_2_7_2_1","first-page":"CD010254","article-title":"Lipid\u2010lowering efficacy of rosuvastatin","author":"Adams S. 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