Drospirenone-containing contraceptive exerts positive effects on cardiac uric acid and PAI-1 but not GSK-3: Improved safety profiles in contraception?

The use of combined oral contraceptives (COC) have been associated with increased risk of adverse cardiovascular events and elevated cardiac and circulating plasminogen activator inhibitor-1 (PAI-1) and glycogen synthase kinase-3 (GSK-3) have been implicated in these events. Contraceptives containing drospirenone, a progestin with anti-androgenic actions may have a positive or neutral effect on cardiac PAI-1 and GSK-3 levels. Studies on the favorable effects of oral contraceptives containing drospirenone when compared with other androgenic contraceptives have not been fully elucidated. We therefore sought to compare the effect of a contraceptive containing ethinyl estradiol and drospirenone (DSP) with a contraceptive containing ethinyl estradiol and levonorgestrel (LVG) on cardiac uric acid (UA), PAI-1, GSK-3 and some hematological parameters. Ten weeks old female Wistar rats were divided into three groups; control (CON), LVG or DSP treated rats. The treatment lasted for 8 weeks. Results showed that LVG and not DSP treatment led to increase in plasma and cardiac tissue UA, plasma and cardiac PAI-1 as well as granulocyte-lymphocyte ratio (GLR) and platelet-lymphocyte ratio (PLR). However, the DSP treatment affected the circulating GSK-3. Taken together, the findings showed that LVG and not DSP affected cardiac UA and PAI-1. These results suggest that COC containing drospirenone appears to have positive effects on cardiac UA and PAI-1 levels but do not affect GSK-3, hence, COC containing drospirenone may be a better and safer means of contraception compared to androgenic contraceptives.