Synergistic Amelioration of Endocrine Dysregulation by Vernonia amygdalina and Tamarindus indica in Letrozole and Diet-induced Polyendocrine Metabolic Ovarian Syndrome in Rats

Background: Polyendocrine metabolic ovarian syndrome (PMOS) is characterised by endocrine and reproductive disturbances involving the hypothalamic–pituitary–ovarian axis. Aim: The present study aimed to evaluate the synergistic effects of Vernonia amygdalina water extract (VAWE) and Tamarindus indica methanol extract (TIME) on HPO axis hormonal parameters in a letrozole and high-fat high-fructose (HF-HFr) diet-induced PMOS rat model. Study Design: This research was an experimental, randomised, controlled in vivo study. Place and Duration of Study: Department of Biochemistry, Lead City University, Ibadan, Nigeria, between October 2024 and August 2025. Methods: PMOS was induced via letrozole (1 mg/kg) and HF-HFr diet for 21 days. Forty-eight (48) female Wistar rats were randomly assigned to eight groups (n=6): normal control, PMOS untreated, positive control (metformin 10 mg/kg + clomiphene citrate 1 mg/kg), VAWE monotherapy (200 mg/kg), TIME monotherapy (400 mg/kg), low-dose combination (VAWE 100 mg/kg + TIME 200 mg/kg), high-dose combination (VAWE 200 mg/kg + TIME 400 mg/kg), and mid-dose combination (VAWE 200 mg/kg + TIME 200 mg/kg). All treatments were administered orally for 21 days. Serum hormones were quantified by ELISA. Estrous cyclicity was monitored by daily vaginal smear cytology. Results: Induction of PMOS resulted in significant hormonal imbalance characterised by elevated testosterone (0.3495 ± 0.0412 vs control 0.2310 ± 0.0189), luteinising hormone (LH: 0.1118 ± 0.005 vs control 0.06275 ± 0.001), and LH/FSH ratio (0.6900 ± 0.04761 vs control 0.2025 ± 0.1025), alongside marked reductions in progesterone (0.04775 ± 0.00275 vs control 0.3688 ± 0.08625) and sex hormone-binding globulin (SHBG: 291.1 ± 72.70 vs control 3604 ± 228.6). Treatment with VAWE 200 mg/kg effectively attenuated testosterone (0.2510 ± 0.01715), suppressed LH (0.06750 ± 0.003), and restored progesterone levels (0.2880 ± 0.03291). Single administration of TIME 400 mg/kg normalised testosterone levels (0.2215 ± 0.03794), restored SHBG (4045 ± 111.2) and improved the LH/FSH ratio (0.3450 ± 0.1025). Polyherbal combinations demonstrated dose-dependent modulation, with the low-dose combination (VAWE 100 mg/kg + TIME 200 mg/kg) showing superior restoration of progesterone (0.2428 ± 0.04125) and LH/FSH balance (0.4625 ± 0.03577) while the mid-dose (200 + 200 mg/kg) combination produced the greatest reduction in serum testosterone (0.1890 ± 0.01273). Conclusions: These findings provide pharmacological justification for the combined ethnomedicinal use of Vernonia amygdalina and Tamarindus indica in reproductive health and warrant further mechanistic and clinical investigation.