Melatonin Attenuates Androgen-Induced Visceral Adiposity in an Experimental Polycystic Ovary Syndrome Model

Introduction: Polycystic ovary syndrome (PCOS) represents a state of androgen-driven metabolic dysregulation where visceral adiposity and inflammation critically define cardiometabolic risk. Visceral adiposity is not a bystander in PCOS; it is an active endocrine organ driving insulin resistance, low-grade inflammation, and androgen persistence. Interventions that reverse adipocyte hypertrophy and inflammatory signaling may therefore alter the metabolic trajectory of PCOS. Beyond its chronobiotic role, melatonin exerts profound metabolic actions via MT1/MT2 receptors in adipose tissue, modulating oxidative stress and inflammatory gene expression. Yet its direct impact on androgen-induced visceral adiposity remains unclear. Aim: The present study aimed to evaluate the effects of melatonin, metformin, and their combination on visceral fat accumulation in a testosterone-induced PCOS rat model. Material and methods: Thirty prepubertal female Wistar rats were randomized into five groups (n=6): control, PCOS (testosterone 20 mg/kg/day), PCOS+metformin (500 mg/kg/day), PCOS+melatonin (2 mg/kg/day), and PCOS+melatonin+metformin. Treatments lasted 36 days. Estrous cyclicity was monitored by daily vaginal cytology, and somatometric parameters were recorded weekly. On day 36, serum, ovaries, and visceral fat were collected for biochemical and histological analysis. Results: Vaginal smear changes and ovarian pathological alteration due to prolonged testosterone exposure confirmed the successful induction of the PCOS model. Measures of central adiposity, including abdominal circumference and the TC/AC ratio, were significantly higher in the PCOS model than in controls (p < 0.001). Abdominal circumference (AC) increase was greatest in the PCOS model (p < 0.001), while all treatment groups showed significant reductions, most notably in the melatonin + metformin group, followed by melatonin monotherapy and then metformin (all p < 0.001 vs. PCOS). Melatonin was more effective than metformin (p=0.029). AC/TC reduction was greatest in the combined treatment group (p < 0.05). Total weight gain among groups did not reach statistical significance. While total visceral fat weight did not differ among groups, histology revealed a marked reduction in adipocyte number in treated animals, most pronounced in the melatonin group (p < 0.033). Conclusion: Our findings identify melatonin as a metabolic modulator of androgen-driven adiposity, supporting its potential as an adjunctive therapy targeting visceral fat and inflammation in PCOS