Romero-Parra, N, Cupeiro, R, Alfaro-Magallanes, VM, Rael, B, Rubio-Arias, JA, Peinado, AB, and Benito, PJ, IronFEMME Study Group. Exercise-induced muscle damage during the menstrual cycle: A systematic review and meta-analysis. J Strength Cond Res 35(2): 549–561, 2021—A strenuous bout of exercise could trigger damage of muscle tissue, and it is not clear how sex hormone fluctuations occurring during the menstrual cycle (MC) affect this response. The aims of this study were to systematically search and assess studies that have evaluated exercise-induced muscle damage (EIMD) in eumenorrheic women over the MC and to perform a meta-analysis to quantify which MC phases display the muscle damage response. The guidelines of the Preferred Reported Items for Systematic Reviews and Meta-Analysis were followed. A total of 19 articles were analyzed in the quantitative synthesis. Included studies examined EIMD in at least one phase of the following MC phases: early follicular phase (EFP), late follicular phase (LFP), or midluteal phase (MLP). The meta-analysis demonstrated differences between MC phases for delayed onset muscle soreness (DOMS) and strength loss (p < 0.05), whereas no differences were observed between MC phases for creatine kinase. The maximum mean differences between pre-excercise and post-exercise for DOMS were EFP: 6.57 (4.42, 8.71), LFP: 5.37 (2.10, 8.63), and MLP: 3.08 (2.22, 3.95), whereas for strength loss were EFP: −3.46 (−4.95, −1.98), LFP: −1.63 (−2.36, −0.89), and MLP: −0.72 (−1.07, −0.36) (p < 0.001). In conclusion, this meta-analysis suggests that hormone fluctuations throughout the MC affect EIMD in terms of DOMS and strength loss. Lower training loads or longer recovery periods could be considered in the EFP, when sex hormone concentrations are lower and women may be more vulnerable to muscle damage, whereas strength conditioning loads could be enhanced in the MLP.

Female steroid hormone fluctuations during the menstrual cycle and exogenous hormones from oral contraceptives may have potential effects on exercise performance. The aim of this study was to investigate the effects of these fluctuations on cardiorespiratory responses during steady-state exercise in women. Twenty-three healthy endurance-trained women performed 40 minutes of running at 75% of their maximal aerobic speed during different phases of the menstrual cycle (n 5 15; early follicular phase, midfollicular phase, and luteal phase) or oral contraceptive cycle (n 5 8; hormonal phase and nonhormonal phase). Ventilatory parameters and heart rate (HR) were measured. Data were analyzed using a mixed linear model. For the eumenorrheic group, significantly higher oxygen uptake (p 5 0.049) and percentage of maximum oxygen uptake (p 5 0.035) were observed during the midfollicular phase compared with the early follicular. Heart rate (p 5 0.004), oxygen ventilatory equivalent (p 5 0.042), carbon dioxide ventilatory equivalent (p 5 0.017), and tidal volume (p 5 0.024) increased during luteal phase in comparison with midfollicular. In oral contraceptive users, ventilation (p 5 0.030), breathing frequency (p 5 0.018), oxygen ventilatory equivalent (p 5 0.032), and carbon dioxide ventilatory equivalent (p 5 0.001) increased during the hormonal phase. No significant differences were found for the rest of the parameters or phases. Both the eumenorrheic group and oral contraceptive group showed a significant increase in some ventilatory parameters during luteal and hormonal phases, respectively, suggesting lower cardiorespiratory efficiency. However, the lack of clinical meaningfulness of these differences and the nondifferences of other physiological variables, indicate that the menstrual cycle had a small impact on submaximal exercise in the current study.

The aim of this study was to evaluate whether the menstrual cycle and its underlying hormonal fluctuations affect muscle damage and inflammation in well-trained females following an eccentric exercise. Nineteen eumenorrheic women performed an eccentric squat-based exercise in the early follicular phase, late follicular phase and mid-luteal phase of their menstrual cycle. Sex hormones and blood markers of muscle damage and inflammation –creatine kinase, myoglobin, lactate dehydrogenase, interleukin-6, tumoral necrosis factor-α, and C reactive protein– were analyzed in each phase. No effect of menstrual cycle phase was observed (p > 0.05), while an interaction for interleukin-6 was shown (p = 0.047). Accordingly, a moderate effect size [0.68 (0.53)–0.84 (0.74)], indicated that interleukin-6 values 2 h post-trial (2.07 ± 1.26 pg/mL) were likely to be higher than baseline (1.59 ± 0.33 pg/mL), 24 h (1.50 ± 0.01 pg/mL) and 48 h (1.54 ± 0.13 pg/mL) in the mid-luteal phase. Blood markers of muscle damage and inflammation were not affected by the menstrual cycle in well-trained women. The eccentric exercise barely triggered muscle damage and hence, no inflammation was observed, possibly due to participants training status. The mid-luteal phase was the only phase reflecting a possible inflammatory response in terms of interleukin-6, although further factors than sex hormones seem to be responsible for this finding.

Background: The increase in exercise levels in the last few years among professional and recreational female athletes has led to an increased scientific interest about sports health and performance in the female athlete population. The purpose of the IronFEMME Study described in this protocol article is to determine the influence of different hormonal profiles on iron metabolism in response to endurance exercise, and the main markers of muscle damage in response to resistance exercise; both in eumenorrheic, oral contraceptive (OC) users and postmenopausal well-trained women. Methods: This project is an observational controlled randomized counterbalanced study. One hundered and four (104) active and healthy women were selected to participate in the IronFEMME Study, 57 of which were eumenorrheic, 31 OC users and 16 postmenopausal. The project consisted of two sections carried out at the same time: iron metabolism (study I) and muscle damage (study II). For the study I, the exercise protocol consisted of an interval running test (eight bouts of 3 min at 85% of the maximal aerobic speed), whereas the study II protocol was an eccentric-based resistance exercise protocol (10 sets of 10 repetitions of plate-loaded barbell parallel back squats at 60% of their one repetition maximum (1RM) with 2 min of recovery between sets). In both studies, eumenorrheic participants were evaluated at three specific moments of the menstrual cycle: early-follicular phase, late-follicular phase and mid-luteal phase; OC users performed the trial at two moments: withdrawal phase and active pill phase. Lastly, postmenopausal women were only tested once, since their hormonal status does not fluctuate. The three-step method was used to verify the menstrual cycle phase: calendar counting, blood test confirmation, and urine-based ovulation kits. Blood samples were obtained to measure sex hormones, iron metabolism parameters, and muscle damage related markers. Discussion: IronFEMME Study has been designed to increase the knowledge regarding the influence of sex hormones on some aspects of the exercise-related female physiology. Iron metabolism and exercise-induced muscle damage will be studied considering the different reproductive status present throughout well-trained females’ lifespan.

The aim of this study was to analyse the impact of sex hormone fluctuations throughout the menstrual cycle on cardiorespiratory response to high-intensity interval exercise in athletes. Twenty-one eumenorrheic endurance-trained females performed an interval running protocol in three menstrual cycle phases: early-follicular phase (EFP), late-follicular phase (LFP) and mid-luteal phase (MLP). It consisted of 8 × 3-min bouts at 85% of their maximal aerobic speed with 90-s recovery at 30% of their maximal aerobic speed. To verify menstrual cycle phase, we applied a three-step method: calendar-based counting, urinary luteinizing hormone measurement and serum hormone analysis. Mixed-linear model for repeated measures showed menstrual cycle impact on ventilatory (EFP: 78.61 ± 11.09; LFP: 76.45 ± 11.37; MLP: 78.59 ± 13.43) and heart rate (EFP: 167.29 ± 11.44; LFP: 169.89 ± 10.62; MLP: 169.89 ± 11.35) response to high-intensity interval exercise (F2.59 = 4.300; p = 0.018 and F2.61 = 4.648; p = 0.013, respectively). Oxygen consumption, carbon dioxide production, respiratory exchange ratio, breathing frequency, energy expenditure, relative perceived exertion and perceived readiness were unaltered by menstrual cycle phase. Most of the cardiorespiratory variables measured appear to be impassive by menstrual cycle phases throughout a high-intensity interval exercise in endurance-trained athletes. It seems that sex hormone fluctuations throughout the menstrual cycle are not high enough to disrupt tissues’ adjustments caused by the high-intensity exercise. Nevertheless, HR based training programs should consider menstrual cycle phase.

This study measured serum markers of iron status in naturally menstruating and oral contraceptive (OC) athletes during the main hormonal milieus of these two profiles to identify potential differences confounding the diagnosis of iron deficiency in female athletes. Resting blood samples were collected from 36 naturally menstruating athletes during the early-follicular phase (EFP), mid-late-follicular phase (MLFP) and mid-luteal phase (MLP) of the menstrual cycle. Simultaneously, blood samples were collected from 24 OC athletes during the withdrawal and active-pill phase of the OC cycle. Serum iron, ferritin, transferrin, transferrin saturation (TSAT), Creactive protein (CRP), interleukin-6 and sex hormones were analyzed. Naturally menstruating athletes showed lower levels of TSAT, iron and transferrin than OC athletes when comparing the bleeding phase of both profiles (p<0.05) as well as when comparing all analyzed phases of the menstrual cycle to the active pill phase of the OC cycle (p<0.05). Interestingly, only lower transferrin was found during MLFP and MLP compared to the withdrawal phase of the OC cycle (p>0.05), with all other iron markers showing no differences (p>0.05). Intracycle variations were also found within both types of cycle, presenting reduced TSAT and iron during menstrual bleeding phases (p<0.05). In conclusion, in OC athletes, serum iron availability, but not serum ferritin, seems higher than in naturally menstruating ones. However, such differences are lost when comparing the MLFP and MLP of the menstrual cycle with the withdrawal phase of the OC cycle. This should be considered in the assessment of iron status in female athletes.

The development of new models of face masks makes it necessary to compare their impact on exercise. Therefore, the aim of this work was to compare the cardiopulmonary response to a maximal incremental test, perceived ventilation, exertion, and comfort using FFP2 or Emotion masks in young female athletes. Thirteen healthy sportswomen (22.08 ± 1.75 years) performed a spirometry, and a graded exercise test on a treadmill, with a JAEGER® Vyntus CPX gas analyzer using an ergospirometry mask (ErgoMask) or wearing the FFP2 or the Emotion mask below the ErgoMask, randomized on 3 consecutive days. Also, menstrual cycle status was monitored to avoid possible intrasubject alterations. The results showed lower values for the ErgoMask+FFP2, compared to ErgoMask or ErgoMask+Emotion, in forced vital capacity (3.8 ± 0.2, 4.5 ± 0.2 and 4.1 ± 0.1 l, respectively); forced expiratory volume in 1 s (3.3 ± 0.2, 3.7 ± 0.2 and 3.5 ± 0.1 l); ventilation (40.9 ± 1.5, 50.6 ± 1.5 and 46.9 ± 1.2 l/min); breathing frequency (32.7 ± 1.1, 37.4 ± 1.1 and 35.3 ± 1.4 bpm); VE/VO2 (30.5 ± 0.7, 34.6 ± 0.9 and 33.6 ± 0.7); VE/VCO2 (32.2 ± 0.6, 36.2 ± 0.9 and 34.4 ± 0.7) and time to exhaustion (492.4 ± 9.7, 521.7 ± 8.6 and 520.1 ± 9.5 s) and higher values in inspiratory time (0.99 ± 0.04, 0.82 ± 0.03 and 0.88 ± 0.03 s). In conclusion, in young healthy female athletes, the Emotion showed better preservation of cardiopulmonary responses than the FFP2.

The use of oral contraceptives (OCs) by female athletes may lead to improved iron status, possibly through the regulation of hepcidin by sex hormones. The present work investigates the response of hepcidin and interleukin‐6 (IL‐6) to an interval exercise in both phases of the OC cycle. Sixteen endurance‐trained OC users (age 25.3 ± 4.7 years; height 162.4 ± 5.7 cm; body mass 56.0 ± 5.7 kg; body fat percentage 24.8 ± 6.0%; peak oxygen consumption [VO2peak]: 47.4 ± 5.5 mL min−1 kg−1) followed an identical interval running protocol during the withdrawal and active pill phases of the OC cycle. This protocol consisted of 8 × 3 minutes bouts at 85% VO2peak speed with 90 seconds recovery intervals. Blood samples were collected pre‐exercise, and at 0 hour, 3 hours, and 24 hours post‐exercise. Pre‐exercise 17β‐estradiol was lower (P = .001) during the active pill than the withdrawal phase (7.91 ± 1.81 vs 29.36 ± 6.45 pg/mL [mean ± SEM]). No differences were seen between the OC phases with respect to hepcidin or IL‐6 concentrations, whether taking all time points together or separately. However, within the withdrawal phase, hepcidin concentrations were higher at 3 hours post‐exercise (3.33 ± 0.95 nmol/L) than at pre‐exercise (1.04 ± 0.20 nmol/L; P = .005) and 0 hour post‐exercise (1.41 ± 0.38 nmol/L; P = .045). Within both OC phases, IL‐6 was higher at 0 hour post‐exercise than at any other time point (P < .05). Similar trends in hepcidin and IL‐6 concentrations were seen at the different time points during both OC phases. OC use led to low 17β‐estradiol concentrations during the active pill phase but did not affect hepcidin. This does not, however, rule out estradiol affecting hepcidin levels.