Detorsion is not innocent: pirfenidone prevents contralateral ovarian damage following ovarian torsion.

Ovarian torsion is a gynecological emergency caused by rotation of the vascular pedicle, leading to ischemia, necrosis, and potential fertility loss. 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 "save or sacrifice" dilemma. Forty female rats were divided into five groups: Healthy, IR, IR + OVX, IR + Pirfenidone 50 mg/kg, and IR + Pirfenidone 100 mg/kg. Ischemia was induced in the left ovary of IR groups; in IR + OVX, the ovary was excised at 3 h, while in other groups, ovaries were reperfused. Treatments continued for 30 days. Ovarian tissues and blood were analyzed histopathologically, biochemically, and molecularly. Ovarian ischemia-reperfusion 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-1β, NLRP3, caspase-1) and fibrotic signaling (SMAD2, SMAD3, TGF-β1), 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.