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Methods: 42 male adult Wistar rats were randomly divided into six equal groups and administered orally with methadone (dose escalation to 50 mg\/kg) or opium tincture (dose escalation to 200 mg\/kg) for 4 or 8 weeks. At the conclusion of treatment, serum testosterone, the relative weights of the prostate and testes, Johnson\u2019s score, and histomorphometric indices such as seminiferous tubule area, germinal epithelium area, and prostatic epithelial height were measured. Findings: Chronic opium tincture treatment significantly decreased serum testosterone, relative testicular and prostatic weights, and testicular histological indicators (P&lt;0.05). Methadone also damaged certain histology measurements but had a lower impact on testosterone. Prostatic epithelial height increased significantly in the 8-week methadone group, whereas all opium groups exhibited notable decreases (P&lt;0.05). Conclusion: Prolonged oral opium tincture causes more detrimental effects on male reproductive function than methadone, whereas extended methadone exposure may lead to prostate-specific structural changes. These findings highlight the need for careful selection and administration of opioid substitution treatments to diminish the risks of reproduction in dependent individuals.<\/jats:p>","DOI":"10.34172\/ahj.1735","type":"journal-article","created":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T10:45:46Z","timestamp":1792061146000},"page":"1735","update-policy":"https:\/\/doi.org\/10.34172\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Comparison of the Long-Term Effects of Opium Tincture and Methadone Syrup on Testicular and Prostate Histology in Male Rats"],"prefix":"10.34172","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-9239-2261","authenticated-orcid":true,"given":"Asma","family":"Shabani","sequence":"first","affiliation":[{"name":"Department of Anatomy, School of Medicine, Birjand University of Medical Sciences, Birjand, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7454-7677","authenticated-orcid":true,"given":"Ali","family":"Sanjari","sequence":"additional","affiliation":[{"name":"Department of Anatomy, School of Medicine, Birjand University of Medical Sciences, Birjand, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2889-8273","authenticated-orcid":true,"given":"Mohammad Hasan","family":"Namaei","sequence":"additional","affiliation":[{"name":"Department of Laboratory Sciences, Faculty of Paramedical and Rehabilitation Sciences, Mashhad University of Medical Sciences, Mashhad, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9193-0056","authenticated-orcid":true,"given":"Mohammad Mehdi","family":"Hassanzadeh-Taheri","sequence":"additional","affiliation":[{"name":"Department of Anatomy, School of Medicine, Birjand University of Medical Sciences, Birjand, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4368-2139","authenticated-orcid":true,"given":"Mehri","family":"Shadi","sequence":"additional","affiliation":[{"name":"Department of Anatomy, School of Medicine, Birjand University of Medical Sciences, Birjand, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"20123","published-online":{"date-parts":[[2026,5,16]]},"reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1016\/j.forsciint.2019.06.006"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-019-0137-5"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2022.855578"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1038\/s41585-024-00868-w"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2021.100768"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.4103\/0019-509x.204755"},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.2903\/j.efsa.2018.5243"},{"key":"R8","doi-asserted-by":"publisher","DOI":"10.22034\/tru.2023.393707.1144"},{"key":"R9","doi-asserted-by":"crossref","unstructured":"Du GH. 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