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

Women with functional hyperandrogenism show both increased markers of oxidative stress and a mild iron overload. Combined oral contraceptives (COC) may worsen redox status in the general population. Since iron depletion ameliorates oxidative stress in other iron overload states, we aimed to address the changes in the redox status of these women as a consequence of COC therapy and of bloodletting, conducting a randomized, controlled, parallel, open-label clinical trial in 33 adult women with polycystic ovary syndrome or idiopathic hyperandrogenism. After three months of treatment with a COC, participants were randomized (1:1) to three scheduled bloodlettings or observation for another nine months. After taking a COC, participants showed a mild decrease in their plasma electrochemical antioxidant capacity, considering fast-acting antioxidants [MD: −1.51 (−2.43 to −0.60) μC, p = 0.002], and slow-acting antioxidants [MD: −1.90 (−2.66 to −1.14) μC, p < 0.001]. Women submitted to bloodletting showed a decrease in their non-enzymatic antioxidant capacity levels (NEAC) throughout the trial, whereas those individuals in the control arm showed a mild increase in these levels at the end of the study (Wilks’ λ: 0.802, F: 3.572, p = 0.041). Decreasing ferritin and plasma hemoglobin during the trial were associated with worse NEAC levels. COC may impair redox status in women with functional hyperandrogenism. Decreasing iron stores by scheduled bloodletting does not override this impairment.