Resumen de Influencia del ciclo menstrual y del uso de anticonceptivos orales en el suministro de oxígeno: rendimiento aeróbico, oxidación de sustratos y metabolismo del hierro (estudio piloto ironfemme)
Introduction: Over the past few decades female participation in sports and physical activity has continued to increase, leading to the great need of develop more research that considers the possible effects of the reproductive sexual hormones of women on different areas affecting aerobic exercise and sport performance. During menstrual cycle, the large hormonal changes that women experience, specially oestrogen and progesterone variations may influence on different factors related to substrate oxidation, cardiorespiratory variables or on the optimization of iron absorption.
In addition, oral contraceptives (OC) are a popular practice in female athletes, assisting in contraception, reduction of premenstrual symptoms, dysmenorrhea or manipulation of the menstrual cycle in order to optimize training sessions and/or competitions seasons. The different doses found over the different OC types may have distinct effects over cardiorespiratory and oxidative responses and iron absorption with respect to a regular menstrual cycle, which may affect aerobic performance, as it is shown in the literature review (Study I). To understand how menstrual cycle and OC contribute to the improvement or deterioration of aerobic exercise may help coaches and in some cases professionals from public health, to optimize athletic performance as well as the health of women athletes.
Objective: The general aim of this doctoral thesis was to review critically the literature to date in relation to the sexual hormones influence over exercise performance (Study I) and to verify the influence of a regular menstrual cycle and OC on the substrate oxidation (Study II), cardiorespiratory parameters (Study III) and iron metabolism (Study IV) after an endurance exercise in women.
Methods: Data for this doctoral thesis were derived from IronFEMME pilot study: "Iron and muscular damage: FEmale Metabolism and MEnstrual cycle during exercise", an observational, transversal and randomized study developed in Spanish population, specifically in healthy and physically active women between 25 and 40 years and carried out throughout 18 months. The study consists of two different groups: women with regular menstrual cycle (n=15) and women with monophasic OC (n = 9). The participants of both groups performed 40 minutes of continuous running at the speed corresponding to 75% of the peak oxygen consumption (VO2peak) during different phases of the menstrual cycle (early follicular phase, mid-follicular phase and luteal phase) or OC cycle (hormonal phase and non- hormonal phase). Prior to this test, a maximal test was performed to determine their VO2peak. The order of the tests for each phase of the menstrual cycle was randomized for both groups and each of them was performed early in the morning. During the steady- state running test protocol, oxygen uptake (VO2) and carbon dioxide production (VCO2) were measured continuously. The relative rates of whole body carbohydrates (CHO) and fat oxidation (FAT) were calculated (Study II). In addition to VO2 and VCO2, other cardiorespiratory variables such as oxygen uptake relative to body mass (VO2/kg), heart rate (HR), ventilation (VE), tidal volume (VT), breathing frequency (BF), ventilatory equivalent for oxygen (VE/VO2) and ventilatory equivalent for carbon dioxide (VE/VCO2) were measured continuously, while the percentage of intensity of VO2peak (%VO2peak) was calculated later (Study III). Finally, different parameters related to iron metabolism: hepcidin, ferritin, transferrin and iron; as well as different inflammatory markers such as interleukin-6 (IL-6) and C-reactive protein (CRP) were measured in baseline levels, 0h and 3h post exercise (Study IV).
Results: There were no differences in the respiratory exchange ratio (RER) for each phase of regular menstrual cycle group (early-follicular phase 0.89±0.01; mid-follicular phase 0.87±0.01 and luteal phase 0.88±0.01; p>0.05) and for participants using OC (hormonal phase 0.91±0.01 and non-hormonal phase 0.89±0.01; p>0.05). However, we found that OC may influence fat oxidation (p=0.018) during the hormonal phase (0.38±0.06 g/min) regarding to non-hormonal phase (0.32±0.06 g/min) (Study II). For women with a regular menstrual cycle significantly higher VO2 (p=0.049) and %VO2peak (p=0.035) were reported during the mid-follicular phase (2439.98±79.27 ml/min and 83.32±1.81 % respectively) compared to early follicular phase (2368.27±79.27 ml/min y 80.80±1.81 %, respectively), whereas during luteal phase higher levels of HR (p=0.004), VE/VO2 (p=0.042), VE/VCO2 (p=0.017) and VT (p=0.024) were found compared to mid-follicular phase. However, no changes over the cycle were observed for VO2/kg, VCO2, VE, and BF (p>0.05). In women taking oral contraceptives VE (p=0.03), BF (p=0.018), VE/VO2 (p=0.032) and VE/VCO2 (p=0.001) were higher during the hormonal phase. No significant differences (p>0.05) were found for VO2, VO2/kg, %VO2peak, VCO2, HR, and VT between the OC phases (Study III). For regular menstrual cycle group, hepcidin, ferritin and transferrin were not different across menstrual cycle phases (p>0.05), while IL-6 and CRP showed a trend during luteal phase and early follicular phase respectively. Iron levels were significantly lower (p=0.009) during early follicular phase (58.62±9.54 μg/dl) regarding to mid-follicular phase (79.46±9.54 μg/dl). IL-6 peak levels were found at 3h post exercise (5.20±0.87 pg/ml; p<0.001) and hepcidin peak levels at 0h post exercise (75.83±6.99 ng/ml; p<0.001). IL-6 was the only variable showing a significant interaction for menstrual cycle phase and time (p=0.014), showing higher IL-6 levels at 3h post-exercise during luteal phase (8.31±1.15 pg/ml) regarding to early follicular phase (3.49±1.15 pg/ml) and mid-follicular phase (3.80±1.15 pg/ml). For OC group, iron levels were significantly higher during hormonal phase (85.04±13.46 μg/dl; p=0.024) and almost significant for ferritin levels (p=0.058). We observed a trend for CRP (p=0.089) during hormonal phase, whereas hepcidin, IL-6 and transferrin levels remained unchanged (p>0.05) throughout OC cycle (Study IV).
Conclusions: The main conclusions indicated that menstrual cycle and OC do not influence substrate oxidation in females. Nevertheless, exogenous hormones from hormonal phase of a monophasic OC cycle may benefit fat oxidation in relation to the non-hormonal phase (Study II). HR and ventilator parameters (VE/VO2; VE/VCO2) were significantly higher during luteal phase regarding to early follicular phase, indicating a lower ventilatory eficiency and a higher cardiovascular strain during this phase. In addition, VO2 absolute levels were increased during mid-follicular phase regarding to early follicular phase, suggesting that progesterone may be not the only factor modifying this parameter. Oral contraceptive group did not present changes in HR and VO2 along the cycle duting a submaximal exercise. However, breathing patterns (VE; VE/VO2; VE/VCO2) were significantly higher during the hormonal phase, suggesting a higher ventilator effort during this phase (Study III). Regular menstrual cycle group did not show changes in hepcidin, ferritin and transferrin; although a decreased iron levels were observed during the early follicular phase, indicating that during menses, the bleeding experienced by females could be the main responsible in iron levels reduction due to the loss of haemoglobin. Moreover, a higher inflammation was shown at 3h post-exercise during luteal phase when progesterone levels were elevated, suggesting that an elevated progesterone presence accompanied by an exercise stimulus may cause more inflammation during luteal phase. A monophasic oral contraceptive cycle did not present changes in hepcidin and IL-6 levels along different phases but it improved iron parameters (iron and ferritin) during hormonal phase (Study IV).
Key words: aerobic exercise; oxygen uptake; menstrual cycle; oral contraceptives; iron; hepcidin.
