Combined estrogen–progestogen but not progestogen-only oral contraceptive alters glucose tolerance and plasma lipid profile in female rats

Abstract

Women are exposed to sex steroids in several formulations such as oral contraceptives (OCs) and hormone replacement therapies. Estrogen is believed to have cardiometabolic protection effect; but its beneficial effects have recently been queried. The aim of the present study was to clarify whether or not the altered glucose tolerance and plasma lipid profile was associated with OC and due to the estrogenic or progestogenic-component and if that was dose-dependent in 7–8 weeks old female rats. Rats were divided into vehicle-treated (control), high dose combined OC-treated (HCOC; receiving 1.5μg ethinyl estradiol/15.0μg norgestrel), low dose combined OC-treated (LCOC; receiving 0.15μg ethinyl estradiol/1.5μg norgestrel), high dose progestogen OC-treated (HOC; receiving 35.0μg levonorgestrel) and low dose progestogen OC-treated (LOC; receiving 3.5μg levonorgestrel) groups. Rats were given (p.o.) vehicle (distilled water), HCOC, LCOC, HOC and LOC daily for 6 weeks. When compared with the controls, HCOC treatment led to significant decreases in glucose tolerance and plasma high-density lipoprotein-cholesterol. However, HCOC-treated and LCOC-treated groups had significantly higher plasma triglyceride levels when compared with the control group. Fasting blood glucose, plasma total cholesterol, and low-density lipoprotein-cholesterol were comparable among groups. Body weight gain appeared to be attenuated by OC treatments, particularly in LOC-treated rats. In conclusion, our findings demonstrate that combined estrogen–progestogen but not progestogen-only OC use resulted in impaired glucose tolerance that was associated with increased triglyceride and decreased high-density lipoprotein-cholesterol. The effects on glucose tolerance and high-density lipoprotein-cholesterol were dose-dependent while that on triglyceride was not.