Received May 08, 2025
Accepted February 20, 2026

Objective: This randomized controlled trial investigated the efficacy of standardized Vitex agnus-castus extract in managing features of PCOS. The primary aim was to assess changes in oxidative stress markers; secondary outcomes included lipid profile, insulin resistance, and clinical signs such as hirsutism and menstrual frequency. Methods: Sixty women with PCOS were randomly assigned to a Vitex group (5.8 mg daily, standardized to 0.42–0.82 mg Aucubin) or placebo for 12 weeks. Dietary habits and physical activity and physical activity were maintained throughout the study. Serum total antioxidant capacity, glutathione peroxidase, reduced glutathione, and other biochemical and clinical parameters were assessed pre- and post-intervention. Between-group differences were analyzed using independent t-tests and ANCOVA. Results: Compared to placebo, Vitex significantly increased total antioxidant capacity (effect size = 13.01), glutathione peroxidase (3.35), reduced glutathione (3.88), total thiol (3.34), and HDL (5.74) (all p < 0.05). It decreased total oxidant status (–6.49), oxidative stress index (–9.30), malondialdehyde (–5.29), fasting blood sugar (–5.10), HOMA-IR (–0.31), LDL (–2.85), ALT (–3.51), and mFG score (–5.38). Menstrual frequency improved (3.51), and left ovarian volume reduced (–0.80). Conclusions: Vitex agnus-castus improved oxidative stress markers and insulin resistance and favorably modulated clinical manifestations of PCOS. These findings suggest a clinically meaningful benefit and support further investigation into Vitex as an adjunctive therapy. Keywords: Polycystic ovary syndrome, Vitex agnus-castus, Oxidative stress, Lipid profile, Insulin resistance, Randomized controlled trial. Trial registration: Iranian Registry of Clinical Trials (IRCT20230222057493N1), registered March 28, 2023. URL: https://irct.behdasht.gov.ir/trial/68740.