Increase of Oxidative Stress is Positively Associated with High-Sensitivity C-Reactive Protein in Women Using Combined Oral Contraceptives: An Observational Study

Abstract

Background Information concerning oxidative stress and low-grade inflammation in oral contraception users is scarce. We investigated relationships of oxidative stress and high-sensitivity C-reactive protein (hsCRP) in women by oral combined contraceptive (OC) use. Methods Caucasian Italian healthy non-obese women (n = 290; 100 OC-users; 190 non-OC-users; mean age 23.2 ± 4.7 years) were analyzed. Blood hydroperoxides, as oxidative stress biomarkers, were assessed by Free Oxygen Radical Test (FORT), and serum hsCRP was determined by routine methods. Results Oxidative stress levels were elevated (≥ 400 FORT Units) in 77.0% and 15.8% of OC-users and non-OC-users, respectively (odds ratio (OR) = 209, 95%CI = 60.9-715.4, p < 0.001); hsCRP levels ≥ 2.0 mg/L were found in 41.0% and 9.5% of OC-users and non-users, respectively (OR = 6.6, 95%CI 3.5–12.4, p < 0.001). Continuous hydroperoxides values in OC-users were 1.7-fold higher compared to non-users (median 472 versus 270 FORT Units, p < 0.001); OC-users had 3.7-fold higher hsCRP values compared to non-OC-users (median 1.31 versus 0.35 mg/L, p < 0.001). Hydroperoxides were strongly positively correlated to hsCRP in all women (rs=0.622, p < 0.001), in OC-users (rs=0.442, p < 0.001), and in non-OC-users (rs=0.426, p < 0.001). Women with hydroperoxides ≥ 400 FORT Units were 8 times as likely to have hsCRP ≥ 2 mg/L. In non-OC-users only, hydroperoxides values were positively correlated with weight and body mass index, but negatively correlated with red meat, fish and chocolate consumption. Conclusions Our cross-sectional observational study is the first finding a strong positive correlation of serum hydroperoxides with hsCRP, a marker of inflammation. Further research is needed to elucidate the potential role of these two biomarkers in OC-use side-effects, like thromboembolism.

Blood oxidative stress biomarkers in women: influence of oral contraception, exercise, and N-acetylcysteine

“…Nonetheless, the nature of the study design (i.e., cross-over experimental) accounted for some of the individual variation. While the participants’ OC contained one of three different progestins, it is not anticipated that this would have influenced the between-group outcomes for our primary biological outcome measures (i.e., oxidative stress) (Cauci et al 2020 ). However, other parameters such as ventilation may be influenced by the androgenicity or the concentration of the progestin and is a limitation to the current design.…”