Reversal of Haemostatic Changes in Letrozole-Induced PCOS Rat Model with Vitamin D Supplementation

Abstract
Background: Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine condition that appears to be associated with a prothrombotic tendency. Hypovitaminosis D is very common in PCOS patients and may exacerbate the metabolic abnormalities. Vitamin D supplementation might produce beneficial effects in these associated metabolic and haemostatic abnormalities.
Aim of Study : The present study was designed to examine the effects of vitamin D supplementation on some metabolic, oxidative stress, inflammatory and haemostatic parameters in letrozole-induced PCOS rat models.
Material and Methods: This study was conducted on 3 groups of adult female albino rats: Group-1: (Control) in which 1ml water was given orally by gavage daily for 21 days, and, group-II: (PCOS induced) in which letrozole was given orally by gavage at a dose of 1mg/kg dissolved in water daily for 21 days, and group-III: (PCOS induced treated with vitamin D) in which letrozole was given orally by gavage with cholecalciferol (200 IU/day) for 21 days. In all groups, serum levels of 25(OH) vitamin D, glucose, insulin, HOMAIR,
lipid profile parameters, Luteinizing hormone (LH), Follicle-stimulating hormone (FSH), testosterone, estradiol,
progesterone, interleukin-6 (IL-6), tumor necrosis factoralpha (TNF-a), plasma fibrinogen, factor VIII (FVIII), Von Willebrand factor (vWF), tissue plasminogen activator (tPA), plasminogen activator inhibitor 1 (PAI-1) activity and Ddimers levels were measured. Bleeding time (BT), whole blood clotting time (WBCT), prothrombin time (PT), activated partial thromboplastin time (aPTT) were also evaluated and ovaries were dissected and used for histopathological examination and evaluating malondialdehyde (MDA), superoxide
dismutase (SOD) and glutathione peroxidase (GPx) levels.
Results: The present study showed that letrozole-induced PCOS rat group (II) showed a statistically significant increase in the serum levels of insulin, glucose and calculated HOMAIR, Cholesterol, Triglyceride, LDL-c, VLDL-c, testosterone, FSH, LH, TNF-a, IL-6, ovarian MDA, plasma FVIII, Vwf, D-dimers, PAI-1 activity and fibrinogen levels (with statistically significant negative correlations with serum vitamin D level) while there were a statistically significant decrease in the serum levels of 25(OH) vitamin D and HDL-c, estradiol,
progesterone, ovarian SOD and GPx, bleeding and clotting times, PT and aPTT when compared to controls (with statistically significant positive correlations with serum vitamin D level). Interestingly, all of the above measures were improved with vitamin D3 supplementation in the treated group (III).
Also, vitamin D3 supplementation reduced the size and number of the cystically dilated ovarian follicles observed in the histopathological examination of letrozole-induced PCOS group.
Conclusion: PCOS are associated with hypovitaminosis D and characterized by metabolic disturbances and a prothrombotic state that can be explained by increased both insulin resistance and inflammatory mediators together with the development of oxidative stress. These changes were improved by vitamin D supplementation.