{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T04:04:39Z","timestamp":1783915479286,"version":"3.55.0"},"reference-count":15,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T00:00:00Z","timestamp":1781740800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T00:00:00Z","timestamp":1781740800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:p>\n                    Pretomanid is a component of the World Health Organization\u2010recommended treatment regimen for drug\u2010resistant tuberculosis in patients aged \u2265\u200914\u2009years. While preclinical rodent studies identified testicular toxicity as a potential clinical liability at elevated doses, no corresponding effects were observed in nonhuman primates nor clinical hormone assessments. This phase 2 clinical trial assessed testicular safety of therapy with bedaquiline, pretomanid, moxifloxacin, and pyrazinamide in 26 adult males with drug\u2010resistant tuberculosis recruited from South Africa and Georgia. The study included 26\u2009weeks of treatment followed by 52\u2009weeks of safety monitoring until study week 78. The primary endpoint measured change in total sperm count from baseline at week 26, with secondary endpoints evaluating sperm concentration, semen volume, and reproductive hormone concentrations. Results demonstrated favorable testicular safety outcomes. Mean total sperm count increased from 48.8 to 68.8\u2009\u00d7\u200910\n                    <jats:sup>6<\/jats:sup>\n                    per ejaculate by week 26. Fifteen participants (68%) showed increased sperm counts, while 17 (77%) exhibited higher sperm concentrations from baseline to week\u201026 Thirteen participants (59%) experienced \u2265\u200950% improvement in both parameters. Two participants demonstrated &gt;\u200950% decreases in total sperm count; however, sperm concentration reductions were &lt;\u200950%, suggesting low semen volume as a factor. Testosterone levels increased from baseline, peaking at week 44, while inhibin B demonstrated steady increases, peaking at week 78. Follicle\u2010stimulating hormone and luteinizing hormone remained stable throughout the study period. All assessable participants achieved sputum culture conversion by week 12. Pharmacokinetic analysis revealed no correlation between pretomanid plasma concentrations and sperm count changes. These findings provide reassurance that pretomanid does not impair human spermatogenesis nor disrupt reproductive hormone homeostasis.\n                  <\/jats:p>","DOI":"10.1002\/cpt.70363","type":"journal-article","created":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T08:37:32Z","timestamp":1781771852000},"page":"501-509","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Preserved Spermatogenesis and Hormonal Function in Men Receiving a Pretomanid Regimen (\n                    <scp>BPaMZ<\/scp>\n                    ) for Pulmonary Drug\u2010Resistant Tuberculosis"],"prefix":"10.1002","volume":"120","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5635-3134","authenticated-orcid":false,"given":"Pauline","family":"Howell","sequence":"first","affiliation":[{"name":"Clinical Health Research Unit (CHRU), Faculty of Health Science University of the Witwatersrand  Johannesburg South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-7383-2495","authenticated-orcid":false,"given":"Antonio","family":"Lombardi","sequence":"additional","affiliation":[{"name":"TB Alliance  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1092-9919","authenticated-orcid":false,"given":"William","family":"Brumskine","sequence":"additional","affiliation":[{"name":"The Aurum Institute NPC  Rustenburg South Africa"},{"name":"Department of Medicine, School of Medicine Vanderbilt University  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9569-7060","authenticated-orcid":false,"given":"Lali","family":"Mikiashvili","sequence":"additional","affiliation":[{"name":"National Center for Tuberculosis and Lung Disease  Tbilisi Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4564-8057","authenticated-orcid":false,"given":"Kim","family":"Boekelheide","sequence":"additional","affiliation":[{"name":"Brown University  Providence Rhode Island USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Moreira","sequence":"additional","affiliation":[{"name":"TB Alliance  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alda","family":"Holsta","sequence":"additional","affiliation":[{"name":"Rho  Riga Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Betteridge","sequence":"additional","affiliation":[{"name":"TB Alliance  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2651-4512","authenticated-orcid":false,"given":"Lindsay","family":"Thompson","sequence":"additional","affiliation":[{"name":"MRC Clinical Trials Unit University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6174-8747","authenticated-orcid":false,"given":"Angela","family":"Crook","sequence":"additional","affiliation":[{"name":"MRC Clinical Trials Unit University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Bruinenberg","sequence":"additional","affiliation":[{"name":"TB Alliance  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Beumont","sequence":"additional","affiliation":[{"name":"TB Alliance  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugene","family":"Sun","sequence":"additional","affiliation":[{"name":"TB Alliance  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0194-3559","authenticated-orcid":false,"given":"Francesca","family":"Conradie","sequence":"additional","affiliation":[{"name":"Isango Lethemba TB Research Unit CHRU, Wits Health Consortium  Gqeberha South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,18]]},"reference":[{"key":"e_1_2_12_1_1","unstructured":"Global tuberculosis report 2025(2025) Geneva: World Health Organization. Licence: CC BY\u2010NC\u2010SA 3.0 IGO."},{"key":"e_1_2_12_2_1","doi-asserted-by":"crossref","unstructured":"Key updates to the treatment of drug\u2010resistant tuberculosis: rapid communication June 2024(2024) Geneva: World Health Organization.https:\/\/doi.org\/10.2471\/B09123.","DOI":"10.2471\/B09123"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1901814"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2119430"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2117166"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.2174\/1381612043383214"},{"key":"e_1_2_12_7_1","first-page":"445","article-title":"Endocrine effects in the hazard assessment of drugs used in animal production","volume":"21","author":"Mantovani A.","year":"2002","journal-title":"J. Exp. Clin. 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