Citrus lemon peel extract versus metformin in testosterone-induced polycystic ovary syndrome: An experimental study

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.

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.

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.

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).

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.