Effect of oral contraception on biotransformation, oxidative stress and oxidative damage

Abstract

The first hormonal oral contraceptive was released in 1960, giving women a more efficient way of controlling pregnancy and family planning. A combined oral contraceptive (COC) consists of an estrogen and a progestin compound. Initially, the concentrations of the hormones in COCs were very high and over the years there was a decline in the concentrations of the hormonal compounds in COCs, as well as the development of physiological similar hormonal compounds. However, the long term effects of COCs are not known. The Biotransformation and Oxidative Stress Status Laboratory (North-West University) found that female patients using a specific COC formulation, namely ethinylestradiol/drospirenone (EE/DRSP) showed characteristically high levels of ROS and 2,3-DHBA, even though the antioxidant potential was high enough to be able to bind and eliminate the ROS – a discovery backed by several studies. High levels of ROS can cause oxidative stress and oxidative damage. A study was designed to determine the effect of the EE/DRSP formulation on female participants using the COC on biotransformation, oxidative stress and oxidative damage. For this study, 20 EE/DRSP users and 19 controls were recruited (NWU-0096-08-A1). Participants were required to take the standard biotransformation loading test. All samples were processed per standard procedures and the concentrations of 8-OHdG, 3-NT and lipid peroxidation were determined additionally. The results confirmed the high levels of ROS, especially 2,3-DHBA in the EE/DRSP group. As a result of the increased ROS levels, the Phase II conjugation reactions, especially glutathionation and glucuronidation, which is the main Phase II reactions for the metabolism of EE, in the EE/DRSP group came under pressure and was systemically depleted. The depletion of the conjugation reactions led to a secondary increase in ROS. The conclusion could be made that the use of the EE/DRSP COC formulation had a negative effect on the biotransformation of its users and could have serious health risks if left untreated. Keywords: biotransformation, oxidative stress, oxidative damage, estrogen, combined oral contraception, ethinylestradiol, drospirenone.