Effects of combined oral contraceptive (Duofem) on some physiological parameters in female Wistar rats

Abstract

Background: Numerous studies have reported a relationship between oral contraceptives use and cardiovascular disease, altered levels of coagulation factors and thrombosis. The goal of this study was to examine the effect of Combined oral contraceptive (COC, Duofem) on some physiological parameters and elucidate possible mechanism of action in female wistar rats.

Methods: Forty (40) female wistar rats aged 10-12 weeks weighing 180-250 g were used for the study. They were divided into four groups (A-D) of 10 rats each comprising 5 treated and 5 control rats. The treated rats received (by intragastric administration), 0.6mg/kg body weight of COC for 36, 48, 60 and 72 days in five-day cycles (four-days treatment with one-day break). The COC was given in 5-day cycles (4-day treatment with 1-day break). An autoanalyzer was used to perform a complete blood count (CBC or FBC). Enzyme-linked immunosorbent assay (ELISA) was used for the quantitative determination of Protein C and S Antigen in citrated rat plasma. Antithrombin (AT) was determined by Chromogenic Assays. Prothrombin time (PT), Activated partial thromboplastin time (APTT) were performed using Sysmex CA-6000 Coagulation Analyzer. Serum electrolytes were determined using Audicom AC99000 and liver function tests by ELISA method. Erythropoietin was determined using rat EPO ELISA kit. Fibrinogen was estimated by Clauss Assay.

Results: There were significant decreases in haemoglobin (Hb), packed cell volume (PCV), Red blood cell (RBC) count, white blood cell (WBC) counts, lymphocytes (L), prothrombin time (PT) concentration, fibrinogen (Fib) concentration, antithrombin (AT) concentration , protein C (PC), protein S (PS), interleukin-6 (IL-6) and interleukin-11 (IL-11) in all treated groups compared to controls (P< 0.05, respectively); in contrast, activities of alkaline phosphate (ALP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) as well as sodium and potassium were increased. There were no significant changes in APTT, mean platelet volume (MPV), EPO concentration, MCH, MCV, MCHC, Neutrophil, Eosinophil, Basophil, Bicarbonate and Chloride in all treated groups compared to controls. Most of the changes in the Physiological parameters were observed in long term exposure group C and group D.

Conclusion: Long term used of combined oral contraceptives may lead to more complications than short time use. COC users should be monitored for some physiological parameters.

Keywords: Combined Oral Contraceptives, Physiological Parameters, Wistar rats