Herawati, Ulfa Nadiya and Annas, Jimmy Yanuar and Widjiati (2026) Citrus lemon peel extract versus metformin in testosterone-induced polycystic ovary syndrome: An experimental study. International Journal of Reproductive BioMedicine, 24 (3). 181 - 192.

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Abstract

Background: Metformin is the standard therapy for metabolic disturbances in polycystic ovary syndrome (PCOS), but its gastrointestinal side effects prompt the search for alternatives. Lemon peel extract (LPE) possesses anti-inflammatory and anti-diabetic properties that may support PCOS management. Objective: To evaluate the effects of LPE, metformin, and their combination on tumor necrosis factor-α (TNF-α), homeostatic model assessment of insulin resistance (HOMA-IR), and fasting blood glucose (FBG) in testosterone-induced PCOS rats. Materials and Methods: An experimental study was conducted on 32 females Rattus norvegicus (12 wk, 130�170 gr), divided into 4 groups (n = 8): untreated PCOS, PCOS + LPE at dose 500 mg/kg, PCOS + metformin at dose 200 mg/kg, and PCOS with combination LPE 500 mg/kg + metformin 200 mg/kg. PCOS was induced with testosterone propionate (10 mg/kg) for 21 days, followed by 14 days of treatment. 24 hr after the last treatment, blood samples were collected to measure TNF-α, insulin and FBG using the enzyme-linked immunoassay method. HOMA-IR was calculated from insulin and FBG levels. Results: LPE significantly reduced TNF-α, HOMA-IR, and FBG compared with the untreated PCOS rats (p < 0.001), no significant differences were observed when compared with metformin administration (TNF-α, p = 0.945; HOMA-IR, p = 0.554; FBG, p = 0.575). Additionally, combination therapy of LPE and metformin resulted in a greater reduction in HOMA-IR and FBG than single therapy (p < 0.05). Conclusion: LPE reduced TNF-α levels, HOMA-IR, and FBG in PCOS rats, with effects comparable to metformin. Interestingly, their effectiveness improves when used in combination. © 2026, Research and Clinical Center for Infertitlity. All rights reserved.

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