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

PURPOSE: To compare physiological responses to submaximal cycling and sprint cycling performance in women using oral contraceptives (WomenOC) and naturally cycling women (WomenNC) and to determine whether N-acetylcysteine (NAC) supplementation mediates these responses. METHODS: Twenty recreationally trained women completed five exercise trials (i.e., an incremental cycling test, a familiarisation trial, a baseline performance trial and two double-blind crossover intervention trials). During the intervention trials participants supplemented with NAC or a placebo 1 h before exercise. Cardiopulmonary parameters and blood biochemistry were assessed during 40 min of fixed-intensity cycling at 105% of gas-exchange threshold and after 1-km cycling time-trial. RESULTS: WomenOC had higher ventilation (ß [95% CI] = 0.07 L·min-1 [0.01, 0.14]), malondialdehydes (ß = 12.00 mmol·L-1 [6.82, 17.17]) and C-reactive protein (1.53 mg·L-1 [0.76, 2.30]), whereas glutathione peroxidase was lower (ß =  22.62 mU·mL-1 [- 41.32, - 3.91]) compared to WomenNC during fixed-intensity cycling. Plasma thiols were higher at all timepoints after NAC ingestion compared to placebo, irrespective of group (all p < 0.001; d = 1.45 to 2.34). For WomenNC but not WomenOC, the exercise-induced increase in malondialdehyde observed in the placebo trial was blunted after NAC ingestion, with lower values at 40 min (p = 0.018; d = 0.73). NAC did not affect cycling time-trial performance. CONCLUSIONS: Blood biomarkers relating to oxidative stress and inflammation are elevated in WomenOC during exercise. There may be an increased strain on the endogenous antioxidant system during exercise, since NAC supplementation in WomenOC did not dampen the exercise-induced increase in malondialdehyde. Future investigations should explore the impact of elevated oxidative stress on exercise adaptations or recovery from exercise in WomenOC.

Temporal changes in blood oxidative stress biomarkers across the menstrual cycle and with oral contraceptive use in active women.

PURPOSE: To examine the temporal changes in blood oxidative stress biomarkers in recreationally-trained women that were naturally-cycling (WomenNC) or using oral contraceptives (WomenOC) across one month. METHODS: Blood samples were acquired at three timepoints of the menstrual cycle (1: early-follicular, 2: late-follicular and 3: mid-luteal) and oral contraceptive packet (1: InactiveOC, 2: Mid-activeOC and 3: Late-activeOC) for determination of estradiol, progesterone, oxidative stress, C-reactive protein (CRP) and other cardiometabolic biomarkers in plasma and serum. RESULTS: There was a Group by Time effect on estradiol (p < 0.001, partial η2 = 0.64) and progesterone (p < 0.001, partial η2 = 0.77). Malondialdehyde, lipid hydroperoxides and CRP concentrations were higher in WomenOC during Late-activeOC compared to InactiveOC (+ 96%, + 23% and + 104%, respectively, p < 0.05). However, there were no changes in these biomarkers across the menstrual cycle in WomenNC (p > 0.05). At all timepoints (i.e., 1, 2 and 3), WomenOC had elevated lipid hydroperoxides (+ 28, + 48% and + 50%) and CRP (+ 71%, + 117% and + 130%) compared to WomenNC (p < 0.05, partial η2 > 0.25). There was no Group by Time effect on non-enzymatic antioxidants or glutathione peroxidase; however, glutathione peroxidase was lower in WomenOC, i.e., main effect of group (p < 0.05, partial η2 > 0.20). CONCLUSION: These findings demonstrate that WomenOC not only have higher oxidative stress and CRP than WomenNC, but also a transient increase across one month of habitual oral contraceptive use. Since changes in oxidative stress and CRP often relate to training stress and recovery, these outcomes may have implications to workload monitoring practices in female athletes.

Reliability of a point-of-care device to determine oxidative stress in whole blood before and after acute exercise: A practical approach for the applied sports sciences.

Measuring alterations in redox homoeostasis in athletes can provide insights into their responses to training such as adaptations or fatigued states. However, redox monitoring is impractical in athletes given the time burden of venepuncture and subsequent laboratory assays. The ability of point-of-care tests (POC): 1) Free Oxygen Radical Test (FORT) and 2) Free Oxygen Radical Defence (FORD), to reliably measure whole blood oxidative stress between days and after exercise is unknown as well as their relationship with laboratory measures (F2-isoprostanes, total antioxidant capacity; TAC). Participants completed two trials performed on separate days comprising blood sampling at rest (n=22) and after treadmill-running (n=14). Between-day CVs for FORT (4.6%) and FORD (4.8%) were acceptable at rest. There was no difference in the between-day magnitude of change in any biomarker from pre- to post-exercise (p>0.05), yet the within-trial change in FORD was variable (trial one: +4.5%, p=0.15; trial two: +6.3%, p<0.05). TAC and FORD were significantly correlated pre- and post-exercise (r=~0.53, p<0.05), whereas F2-isoprostanes and FORT had a significant correlation pre-exercise only (r=0.45, p=0.03). Overall, the POC tests are reliable and could be used for baseline longitudinal redox monitoring. More data is required on POC tests for assessing redox perturbations induced by exercise.

Cerebral oxygenation declines but does not impair peak oxygen uptake during incremental cycling in women using oral contraceptives.

PURPOSE: To compare prefrontal cortex oxygenation in recreationally-active women using oral contraceptives (WomenOC; n = 8) to women with a natural menstrual cycle (WomenNC; n = 8) during incremental exercise to exhaustion. METHODS: Participants performed incremental cycling to exhaustion to determine lactate threshold 1 (LT1) and 2 (LT2) and peak oxygen uptake (VO2peak). Prefrontal cortex oxygenation was monitored via near-infrared spectroscopy through concentration changes in oxy-haemoglobin (Δ[HbO2]), deoxy-haemoglobin (Δ[HHb]), total-haemoglobin (Δ[tHb]) and tissue saturation index (TSI). RESULTS: 17ß-oestradiol and progesterone were lower in WomenOC (35 ± 26; 318 ± 127 pmol·L-1, respectively) than WomenNC (261 ± 156; 858 ± 541 pmol·L-1, respectively). There were no differences in full blood examination results or serum nitric oxide (p > 0.05). However, WomenOC presented lower concentrations in ferric-reducing ability of plasma (- 8%; effect size; ES - 0.52 ± 0.61), bilirubin (- 32%; ES - 0.56 ± 0.62) and uric acid (- 17%; ES - 0.53 ± 0.61). Cardiopulmonary parameters were similar between groups during cycling, including VO2peak (p = 0.99). While there was a significant effect of time on all parameters measured by near-infrared spectroscopy during incremental cycling, there was no effect of OC at LT1, LT2 or exhaustion calculated as a change from baseline (TSI; p = 0.096, Δ[HbO2]; p = 0.143, Δ[HHb]; p = 0.085 and Δ[tHb]; p = 0.226). The change in TSI from LT1 to LT2 was significantly different between groups (WomenNC; mean difference + 2.06%, WomenOC; mean difference - 1.73%; p = 0.003). CONCLUSION: Prefrontal tissue oxygenation declined at a lower relative exercise intensity in WomenOC as compared to WomenNC, however, this did not influence VO2peak. The results provide the first evidence for variance in the cerebral oxygenation response to exercise, which may be associated with female sex hormones.