PLATELET FUNCTION

Polycystic Ovary Syndrome (PCOS) is a prevalent endocrine disorder characterized by reproductive dysfunction, including anovulation and adverse ovarian remodeling, as well as systemic complications such as a prothrombotic state involving platelet dysfunction. This study was designed to investigate a dual-pronged therapeutic strategy targeting both the systemic metabolic and local ovarian aspects of the syndrome. This study aimed to evaluate the individual and combined effects of metformin and simvastatin on ovarian histology and surrogate markers of platelet function in a letrozole-induced Sprague Dawley rat model of PCOS. PCOS was induced in female Sprague Dawley rats via oral administration of letrozole (1 mg/kg) for 21 days. The rats were subsequently randomized into five groups: a healthy control group, an untreated PCOS group, and three treatment groups receiving simvastatin (20 mg/kg), metformin (300 mg/kg), or a combination of simvastatin and metformin for 28 days. At the end of the treatment period, ovarian tissues were collected for histopathological examination using Hematoxylin and Eosin (H&E) staining, and whole blood was analyzed for platelet indices, including Platelet Count, Mean Platelet Volume (MPV), and Platelet Distribution Width (PDW). Histopathological analysis revealed that the untreated PCOS group developed multiple cystic follicles and an absence of corpora lutea, confirming an anovulatory state. Metformin monotherapy significantly improved ovarian architecture and restored ovulation, evidenced by the presence of multiple corpora lutea. Simvastatin monotherapy showed partial amelioration, with a reduction in cystic follicles but scarce corpora lutea. The combination therapy demonstrated a potent synergistic effect, resulting in a near-complete normalization of ovarian histology that closely resembled the healthy control group, with numerous developing follicles and corpora lutea. Hematological analysis showed no significant differences in plateLet count or MPV across the treated groups compared to the untreated PCOS group. However, metformin monotherapy led to a paradoxical and statistically significant increase in PDW and Platelet-Large Cell Ratio (P-LCR) (P < 0.05). In concluson, Metformin and simvastatin exert distinct effects on both hematological and ovarian parameters in PCOS-induced rats. Metformin monotherapy showed a significant impact on platelet morphology, increasing PDW and P-LCR. Furthermore, it was highly effective in restoring ovarian cytoarchitecture, evidenced by the absence of cysts. Simvastatin monotherapy also improved ovarian morphology, reducing cystic structures, but showed no significant effect on platelet indices. Critically, the combination therapy presented a complex interaction, showing limited efficacy in resolving ovarian cysts and no significant improvement in platelet parameters compared to monotherapies. These findings suggest that while both drugs are beneficial, their mechanisms may not be synergistic when combined in this mode