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.
Highlights
The main outcomes of the present study are: (1) Elevated oxidative stress levels were found in non-athlete oral combined contraceptive (OC)-users belonging to the general population of healthy young women; (2) OC-use resulted in chronic inflammation, confirming previous studies performed in lower number of women or different ethnic groups; (3) Oxidative stress and high-sensitivity C-reactive protein (hsCRP) were strongly correlated; (4) Body mass and some alimentary habits modulated oxidative stress in non-OC-users only
In OC-users we found a higher frequency of elevated oxidative stress and inflammation compared to non-OC-users. dos Santos and colleagues [31] hypothesized that several mechanisms, including oxidative stress, elevate inflammation in hormonal contraception users, suggesting a causative role of oxidative stress in blood hsCRP increase
We found very high oxidative stress in the vast majority of OC-users (77% of them had Free Oxygen Radical Test (FORT) ≥ 400 Units)
Summary
The biological pathways and the biomarkers associated with the side effects of hormonal contraception remain elusive and require additional research. Large studies and meta-analysis have assessed the association of oral combined contraceptive (OC) use with major complications, mainly cardiovascular diseases (CVDs) like arterial and venous thromboembolism (VTE), myocardial infarction, ischemic stroke, pulmonary embolism, peripheral arterial disease, and sudden cardiac death [1,2,3,4,5,6,7,8,9,10,11] and some types of cancer including breast, uterine cervix, as well as liver and bile duct cancers [12,13,14]. Some evidence shows a correlation of OC use with mood disorders and depression [16,17]
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