Oxidative Stress Is Increased in Combined Oral Contraceptives Users and Is Positively Associated with High-Sensitivity C-Reactive Protein

Abstract

Information concerning the mechanisms underlying oxidative stress and low-grade inflammation in young healthy women predisposing eventually to future diseases is scarce. We investigated the relationship of oxidative stress and high-sensitivity C-reactive protein (hsCRP) in fertile-age women by oral combined contraceptive (OC) use. 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). Serum hsCRP was determined by an ultra-sensitive method (hsCRP). Markedly elevated oxidative stress (≥400 FORT Units) was found in 77.0% of OC-users and 1.6% of non-OC-users, odds ratio (OR) = 209, 95% CI = 60.9–715.4, p < 0.001. Elevated hsCRP levels ≥ 2.0 mg/L, considered risky for cardiovascular diseases (CVDs), were found in 41.0% of OC-users and 9.5% of non-OC-users, OR = 6.6, 95%CI 3.5–12.4, 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 eight 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. Our research is the first finding a strong positive correlation of serum hydroperoxides with hsCRP, a marker of low-grade chronic inflammation, in young healthy women. Further research is needed to elucidate the potential role of these two biomarkers in OC-use associated side-effects, like thromboembolism and other CVDs.

Health Status Is Affected, and Phase I/II Biotransformation Activity Altered in Young Women Using Oral Contraceptives Containing Drospirenone/Ethinyl Estradiol

“…Both a disturbed biotransformation homeostasis and oxidative stress have been linked to various health problems and disease states [29,56]. In COC users specifically, oxidative stress has been associated with increased high-sensitivity C-reactive protein (hsCRP), a marker of low-grade chronic inflammation [57]. In line with numerous other studies, we report here the occurrence of oxidative stress with COC use.…”

Effect of Iron Depletion by Bloodletting vs. Observation on Oxidative Stress Biomarkers of Women with Functional Hyperandrogenism Taking a Combined Oral Contraceptive: A Randomized Clinical Trial

“…In this scenario, the effect of COC-and their different compounds-on the redox status of hyperandrogenic women becomes an important topic. Although hormonal replace-ment therapy may prevent oxidative damage in postmenopausal women, COC increases oxidative status in young users from the general population [27,38]. Cytochrome P450 1A2 activity is inhibited by COC, whereas enzymes involved in phase 2 biotransformations are induced in COC users [28].…”

“…After extensive first-pass intestinal and hepatic metabolism [24], the estrogenic -most commonly, 17α-ethinylestradiol (EE)-and progestogenic compounds of oral contraceptives undergo phase 1 and 2 metabolic reactions to be mainly excreted in feces as glucuronide conjugates [25]. The use of COC may affect the balance between phase 1 and 2 biotransformations facilitating oxidative stress [26,27]. Furthermore, the ferric reducing ability of plasma-a measure of antioxidant capacity-appears to be reduced in COC users [28].…”

Association between Oral Contraceptive Use and the High-Sensitivity C-Reactive Protein Level in Premenopausal Korean Women

“…However, this study has some limitations. Given the complexity of factors influencing serum hs-CRP levels, additional factors, including oxidative stress [ 35 ] and associated comorbidities, were likely not considered in the model established here. Factors such as the prevalence of CVDs or type 2 diabetes, use of anti-inflammatory drugs, and consumption of antioxidant foods or supplements need to be considered in future studies.…”