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Management remains controversial, particularly regarding oophorectomy versus ovarian preservation. Detorsed ovaries continue cytokine secretion, impairing contralateral ovarian function, and no protective therapy currently exists. This study aimed to compare oophorectomy and detorsion strategies and to determine whether post-detorsion long-term pirfenidone therapy preserves ovarian function, thereby providing experimental resolution to the clinically pivotal \u201csave or sacrifice\u201d dilemma. Forty female rats were divided into five groups: Healthy, IR, IR\u2009+\u2009OVX, IR\u2009+\u2009Pirfenidone 50\u00a0mg\/kg, and IR\u2009+\u2009Pirfenidone 100\u00a0mg\/kg. Ischemia was induced in the left ovary of IR groups; in IR\u2009+\u2009OVX, the ovary was excised at 3\u00a0h, while in other groups, ovaries were reperfused. Treatments continued for 30\u00a0days. Ovarian tissues and blood were analyzed histopathologically, biochemically, and molecularly.\u00a0Ovarian ischemia\u2013reperfusion induced a persistent inflammatory and profibrotic response not only in the ischemic ovary but also in the contralateral ovary, leading to reduced estrogen levels and marked histopathological damage. Importantly, detorsion alone did not prevent contralateral injury, whereas oophorectomy attenuated molecular alterations. Post-detorsion pirfenidone therapy dose-dependently restored estrogen production, suppressed inflammasome activation (IL-1\u03b2, NLRP3, caspase-1) and fibrotic signaling (SMAD2, SMAD3, TGF-\u03b21), and preserved normal follicular architecture in both ovaries. These findings demonstrate that the detorsed ovary remains a biologically active source of injury and identify pirfenidone as a potential adjunct therapy capable of protecting ovarian function after torsion.<\/jats:p>","DOI":"10.1007\/s00210-026-05174-3","type":"journal-article","created":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T04:33:19Z","timestamp":1773376399000},"page":"12507-12519","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Detorsion is not innocent: pirfenidone prevents contralateral ovarian damage following ovarian torsion"],"prefix":"10.1007","volume":"399","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2028-6603","authenticated-orcid":false,"given":"Hamza","family":"Halici","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4281-0103","authenticated-orcid":false,"given":"Zeynep","family":"Karakoy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9636-1753","authenticated-orcid":false,"given":"Emir Enis","family":"Yurdgulu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-6007-694X","authenticated-orcid":false,"given":"Yusuf Anil","family":"Ay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0836-7205","authenticated-orcid":false,"given":"Elif","family":"Cadirci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0715-2707","authenticated-orcid":false,"given":"Erdem","family":"Toktay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8052-5821","authenticated-orcid":false,"given":"Betul","family":"Kavas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,13]]},"reference":[{"key":"5174_CR1","doi-asserted-by":"publisher","first-page":"1583","DOI":"10.1093\/jpp\/rgaf066","volume":"77","author":"AM Abdel-Aziz","year":"2025","unstructured":"Abdel-Aziz AM, Hassan M, Thabit DM, Said S, Shawky HA, Elsayed SH, Khalaf HM (2025) Protective effect of pirfenidone against ovarian ischemia\/reperfusion injury in rats via modulation of TLR4\/p38 MAPK\/IL-1beta and HIF-1alpha\/VEGF-A signaling pathways. 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