Time-restricted eating and supervised exercise for improving hepatic steatosis and cardiometabolic health in adults with obesity: protocol for the TEMPUS randomised controlled trial.

INTRODUCTION: Metabolic dysfunction-associated steatotic liver disease is a major public health problem considering its high prevalence and its strong association with extrahepatic diseases. Implementing strategies based on an intermittent fasting approach and supervised exercise may mitigate the risks. This study aims to investigate the effects of a 12-week time-restricted eating (TRE) intervention combined with a supervised exercise intervention, compared with TRE or supervised exercise alone and with a usual-care control group, on hepatic fat (primary outcome) and cardiometabolic health (secondary outcomes) in adults with obesity. METHODS AND ANALYSIS: An anticipated 184 adults with obesity (50% women) will be recruited from Granada (south of Spain) for this parallel-group, randomised controlled trial (TEMPUS). Participants will be randomly designated to usual care, TRE alone, supervised exercise alone or TRE combined with supervised exercise, using a parallel design with a 1:1:1:1 allocation ratio. The TRE and TRE combined with supervised exercise groups will select an 8-hour eating window before the intervention and will maintain it over the intervention. The exercise alone and TRE combined with exercise groups will perform 24 sessions (2 sessions per week+walking intervention) of supervised exercise combining resistance and aerobic high-intensity interval training. All participants will receive nutritional counselling throughout the intervention. The primary outcome is change from baseline to 12 weeks in hepatic fat; secondary outcomes include measures of cardiometabolic health. ETHICS AND DISSEMINATION: This study was approved by Granada Provincial Research Ethics Committee (CEI Granada-0365-N-23). All participants will be asked to provide written informed consent. The findings will be disseminated in scientific journals and at international scientific conferences. TRIAL REGISTRATION NUMBER: NCT05897073.

Exercise influence on monocarboxylate transporter 1 (MCT1) and 4 (MCT4) in the skeletal muscle: A systematic review.

This review aims to systematically analyze the effect of exercise on muscle MCT protein levels and mRNA expression of their respective genes, considering exercise intensity, and duration (single-exercise session and training program) in humans and rodents, to observe whether both models offer aligned results. The review also aims to report methodological aspects that need to be improved in future studies. A systematic search was conducted in the PubMed and Web of Science databases, and the Preferred Reporting Items for Systematic review and Meta-Analyses (PRISMA) checklist was followed. After applying inclusion and exclusion criteria, 41 studies were included and evaluated using the Cochrane collaboration tool for risk of bias assessment. The main findings indicate that exercise is a powerful stimulus to increase MCT1 protein content in human muscle. MCT4 protein level increases can also be observed after a training program, although its responsiveness is lower compared to MCT1. Both transporters seem to change independently of exercise intensity, but the responses that occur with each intensity and each duration need to be better defined. The effect of exercise on muscle mRNA results is less defined, and more research is needed especially in humans. Moreover, results in rodents only agree with human results on the effect of a training program on MCT1 protein levels, indicating increases in both. Finally, we addressed important and feasible methodological aspects to improve the design of future studies.

Efficacy of different 8 h time-restricted eating schedules on visceral adipose tissue and cardiometabolic health: A study protocol.

BACKGROUND AND AIMS: To investigate the efficacy and feasibility of three different 8 h time-restricted eating (TRE) schedules (i.e., early, late, and self-selected) compared to each other and to a usual-care (UC) intervention on visceral adipose tissue (VAT) and cardiometabolic health in men and women. METHODS AND RESULTS: Anticipated 208 adults (50% women) aged 30-60 years, with overweight/obesity (25 ≤ BMI<40 kg/m2) and with mild metabolic impairments will be recruited for this parallel-group, multicenter randomized controlled trial. Participants will be randomly allocated (1:1:1:1) to one of four groups for 12 weeks: UC, early TRE, late TRE or self-selected TRE. The UC group will maintain their habitual eating window and receive, as well as the TRE groups, healthy lifestyle education for weight management. The early TRE group will start eating not later than 10:00, and the late TRE group not before 13:00. The self-selected TRE group will select an 8 h eating window before the intervention and maintain it over the intervention. The primary outcome is changes in VAT, whereas secondary outcomes include body composition and cardiometabolic risk factors. CONCLUSION: This study will determine whether the timing of the eating window during TRE impacts its efficacy on VAT, body composition and cardiometabolic risk factors and provide insights about its feasibility.

Response to physical activity of females with multiple sclerosis throughout the menstrual cycle: a protocol for a randomised crossover trial (EMMA Project).

The relationship between multiple sclerosis (MS) and females is a crucial aspect in the development of the disease, with the ovarian hormonal cycle being a sensitive stage, especially in females with relapsing-remitting multiple sclerosis. The objectives of the study are to identify moderating variables that modify satisfaction with physical activity practice throughout the menstrual cycle (MC) in females in or out of their MC, during high-intensity interval training (HIIT) and strength training sessions and to compare the acute effects of different types of physical activity sessions in females with and without MS. This protocol is the methodology used in the EMMA Study, a randomised, single-blind crossover trial study conducted in females with MS who were matched 1:1, based on age, lifestyle factors and country of residence, with females without MS, to analyse the effect of physical activity practice on satisfaction, functionality, fatigue and inflammatory profile through their MC. Participants will visit the facilities approximately 10 times (4 preliminary familiarisation visits and 6 visits to carry out a physical activity session in each phase of the MC) for 3-4 months. A total sample of 30 females (15 females without MS and 15 with MS) is necessary for the study. The evaluation will comprise clinical, nutritional and psychological interviews, including different variables. It is hypothesised during the luteal phase, females with MS are expected to exhibit different acute responses to HIIT and strength training sessions as compared with females without the disease. Before starting the study, all participants will read and sign an informed consent form. Trial registration number: This research protocol is registered with ClinicalTrials.gov to ensure transparency and accessibility of study information (NCT06105463). The university's ethics committee number for this study is UALBIO2022/048.

The ergogenic effects of acute carbohydrate feeding on endurance performance: a systematic review, meta-analysis and meta-regression.

A systematic review with meta-analysis was conducted to analyze the effect of carbohydrate (CHO) intake during exercise and some variables that could moderate this effect on endurance performance. We included 136 studies examining the effect of CHO ingestion during endurance exercise in the meta-analysis. The overall effect on performance showed a significant increase after CHO intake compared to the placebo/control groups. A larger effect of CHO consumption is observed in time to exhaustion than in time trials performance test. Moreover, the effectiveness of CHO supplementation was greater the longer the duration of the events. Also, there seems to be a higher effect of CHO intake in lower trained than in higher trained participants. In contrast, the magnitude of performance change of CHO intake is not affected by the dosage, ergometer used, the type of intake of the CHO ingestion and the type of CHO. In addition, a lower rate of perceived exertion and higher power and heart rate are significantly associated with the ingestion of CHO during endurance exercise. These results reinforce that acute CHO feeding is an effective strategy for improving endurance performance, especially, in less trained subjects participating in time to exhaustion tests of longer durations.

Serum iron availability, but not iron stores, is lower in naturally menstruating than in oral contraceptive athletes.

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), C-reactive 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.Highlights Naturally menstruating athletes present lower TSAT, iron and transferrin in all analyzed phases of the menstrual cycle compared to OC athletes during their active pill phase. However, both the mid-late follicular and mid-luteal phases of the menstrual cycle do not differ from the withdrawal phase of the oral contraceptive cycle.Intracycle variations are found for TSAT and iron in both naturally menstruating and oral contraceptive athletes, which are mainly driven by a reduction in TSAT and iron during menstrual bleeding phases.As serum iron availability changes significantly as a function of the athlete's hormonal status, it should be considered in the assessment of the athlete's iron status as well as standardise the phase of the menstrual cycle in which to assess iron markers to avoid misdiagnosis or misleading results.In contrast, the assessment of iron stores through serum ferritin is substantially stable and the athlete's hormonal status does not seem to be of relevance for this purpose.

Influence of oral contraceptive phase on cardiorespiratory response to exercise in endurance-trained athletes.

OBJECTIVE: The aim of the study was to analyse the cardiorespiratory response to exercise during an oral contraceptive (OC) cycle in endurance-trained women. METHODS: Sixteen low-dose monophasic OC pill (OCP) users performed an interval-running protocol. The protocol consisted of eight 3 min bouts at 85% of participants' maximal aerobic speed (vV̇o2peak) with a 90s recovery at 30% vV̇o2peak in two OC phases: a withdrawal phase (WP) and an active pill phase (APP). The non-parametric Wilcoxon test was applied to analyse differences (p < 0.05) in performance variables between OC cycle phases. RESULTS: Throughout the high-intensity intervals, higher ventilation (WP 80.90 ± 11.49 L/min, APP 83.10 ± 13.33 L/min; p < 0.001) and relative perceived exertion (WP 14.51 ± 2.58, APP 15.11 ± 3.11; p = 0.001) during the APP were found, whereas carbon dioxide production (WP 2040.92 ± 262.93 mL/min, APP 2010.25 ± 305.68 mL/min; p = 0.003) was higher in the WP. During the active recovery intervals, ventilation (WP 65.78 ± 9.90 L/min, APP 67.88 ± 12.66 L/min; p < 0.001) was higher in the APP, while heart rate (WP 159.93 ± 10.26 bpm, APP 159.74 ± 12.83 bpm; p = 0.029) was higher in the WP. CONCLUSION: An increase in ventilation occurs during the APP, which is accompanied by higher perceived exertion. Therefore, coaches and athletes should be aware of these variations, especially perceived exertion, in regard to women's training programmes, in order to improve their performance, wellness and adherence to physical activity.

Cardiorespiratory response to high intensity interval exercise inendurance-trained postmenopausal women

Objetivo: Analizar la respuesta cardiorrespiratoria en mujeres deportistas postmenopáusicas y compararla con la de las eumenorreicas. Material y método: Veintiuna mujeres eumenorreicas (30,5±6,5 años, 58,4±8,7 kg, 25,2±6,7% masa grasa, 48,4±4,4 ml/kg/min V̇O2peak) y trece postmenopáusicas (51,3±3,6 años, 54,1±4,1 kg, 24,2±5,2% masa grasa, 46,01±9,8 ml/kg/min V̇O2peak) entrenadas realizaron un protocolo de interválico de alta intensidad. Éste consistió en 8 series de 3 minutos al 85% con descansos de 90 segundos al 30% de su velocidad aeróbica máxima. Las mujeres eumenorreicas realizaron el protocolo en su fase folicular temprana. Las variables cardiorrespiratorias fueron constantemente monitorizadas a lo largo del protocolo. Resultados: El test de U Mann-Whitney mostró que la respuesta cardiorrespiratoria en el protocolo interválico fue menor en las mujeres postmenopáusicas comparado con las eumenorreicas para la ventilación (66,9±10,1 vs 78,6±11,1 l/min; p<0,001), consumo de oxígeno (33,7±3,9 vs 38,6±4,1 ml/kg/min; p<0,001), porcentaje del consumo máximo de oxígeno (79,6±5,3 vs 76,0±10,6 %; p=0,003), frecuencia cardiaca (154,6±9,5 vs 167,3±11,4 lpm; p<0,001) y producción de dióxido de carbono (1914.8±248,9 vs 2127,5±296,8 ml/min; p<0,001). Por el contrario, el porcentaje de la máxima producción de dióxido de carbono (60.6±15.0 vs 65,3±8,9 %; p=0,010), cociente respiratorio (1,03±0,08 vs 0,96±0,06; p<0,001) y el porcentaje del máximo cociente respiratorio (75,4±19,0 vs 83,3±8,2 %; p<0,001) fue mayor en el grupo de postmenopáusicas. Por último, el porcentaje de la frecuencia cardiaca máxima (91,9±1,7 vs 91,1±2,4 %, p=0,443) y el porcentaje de la ventilación máxima (71,9±6,7 vs 71,1±8,4 %, p=0,138) no mostraron diferencias entre grupos.(AU)

Objectives: To evaluate the cardiorespiratory response to high-intensity interval exercise in endurance-trained postmeno­pausal women and compare it with their counterparts eumenorrheic females. Material and method: Twenty-one eumenorrheic (30.5±6.5 years, 58.4±8.7 kg, 25.2±6.7% fat mass, 48.4±4.4 ml/kg/min V̇O2peak) and thirteen postmenopausal (51.3±3.6 years, 54.1±4.1 kg, 24.2±5.2% fat mass, 46.01±9.8 ml/kg/min V̇O2peak) endurance-trained women performed a high-intensity interval running protocol consisted of 8 bouts of 3-min at 85% with 90-s recovery at 30% of their maximal aerobic speed. It was carried out in the early-follicular phase for the eumenorrheic group and at any time for the postmenopausal group. Cardiorespiratory variables were continuously monitored throughout the protocol. Results: The Mann–Whitney U test reported lower values in postmenopausal women compared to eumenorrheic females for ventilation (66.9±10.1 vs 78.6±11.1 l/min; p<0.001), oxygen consumption (33.7±3.9 vs 38.6±4.1 ml/kg/min; p<0.001), % maximal oxygen consumption (79.6±5.3 vs 76.0±10.6 %; p=0.003), heart rate (154.6±9.5 vs 167.3±11.4 bpm; p<0.001) and carbon dioxide production (1914.8±248.9 vs 2127.5±296.8 ml/min; p<0.001). On the contrary, % maximal carbon dioxide production (60.6±15.0 vs 65.3±8.9 %; p=0.010), respiratory exchange ratio (1.03±0.08 vs 0.96±0.06; p<0.001) and % maximal respiratory exchange ratio (75.4±19.0 vs 83.3±8.2 %; p<0.001) were higher in the postmenopausal group. Finally, % maximal heart rate (91.9±1.7 vs 91.1±2.4 %, p=0.443) and % maximal ventilation (71.9±6.7 vs 71.1±8.4 %, p=0.138) lacked of difference between study groups.(AU)

Cardiorespiratory Responses to Endurance Exercise Over the Menstrual Cycle and With Oral Contraceptive Use.

ABSTRACT: Barba-Moreno, L, Cupeiro, R, Romero-Parra, N, Janse de Jonge, XA, and Peinado, AB. Cardiorespiratory Responses to Endurance Exercise Over the Menstrual Cycle and With Oral Contraceptive Use. J Strength Cond Res 36(2): 392-399, 2022-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 = 15; early follicular phase, midfollicular phase, and luteal phase) or oral contraceptive cycle (n = 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 = 0.049) and percentage of maximum oxygen uptake (p = 0.035) were observed during the midfollicular phase compared with the early follicular. Heart rate (p = 0.004), oxygen ventilatory equivalent (p = 0.042), carbon dioxide ventilatory equivalent (p = 0.017), and tidal volume (p = 0.024) increased during luteal phase in comparison with midfollicular. In oral contraceptive users, ventilation (p = 0.030), breathing frequency (p = 0.018), oxygen ventilatory equivalent (p = 0.032), and carbon dioxide ventilatory equivalent (p = 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.

Hepcidin and interleukin-6 responses to endurance exercise over the menstrual cycle.

The aim of the current study was to investigate iron metabolism in endurance trained women through the interleukin-6, hepcidin and iron responses to exercise along different endogenous hormonal states. Fifteen women performed 40 min treadmill running trials at 75% vVO2peak during three specific phases of the menstrual cycle: early follicular phase (day 3 ± 0.85), mid-follicular phase (day 8 ± 1.09) and luteal phase (day 21 ± 1.87). Venous blood samples were taken pre-, 0 h post- and 3 h post-exercise. Interleukin-6 reported a significant interaction for menstrual cycle phase and time (p=0.014), showing higher interleukin-6 levels at 3 h post-exercise during luteal phase compared to the early follicular phase (p=0.004) and the mid-follicular phase (p=0.002). Iron levels were significantly lower (p=0.009) during the early follicular phase compared to the mid-follicular phase. However, hepcidin levels were not different across menstrual cycle phases (p>0.05). The time-course for hepcidin and interleukin-6 responses to exercise was different from the literature, since hepcidin peak levels occurred at 0 h post-exercise, whereas the highest interleukin-6 levels occurred at 3 h post-exercise. We concluded that menstrual cycle phases may alter interleukin-6 production causing a higher inflammation when progesterone levels are elevated (days 19-21). Moreover, during the early follicular phase a significant reduction of iron levels is observed potentially due to a loss of haemoglobin through menses. According to our results, high intensity exercises should be carefully monitored in these phases in order not to further compromise iron stores.

Exercise-Induced Muscle Damage in Postmenopausal Well-Trained Women.

BACKGROUND: Sex hormone deprivation derived from menopause may affect exercise-induced muscle damage (EIMD). No studies have previously evaluated this response between postmpenopausal and premenopausal eumenorrheic women over the menstrual cycle. HYPOTHESIS: Postmenopausal women will present higher EIMD markers than premenopausal women, especially in comparison with the menstrual cycle phases where sex hormone concentrations are higher. STUDY DESIGN: Cross-sectional study. LEVEL OF EVIDENCE: Level 3. METHODS: Thirteen postmenopausal and 19 eumenorrheic women, all of them resistance-trained, performed an eccentric squat-based exercise. The postmenopausal group performed 1 bout of exercise, while the eumenorrheic group performed 3 bouts coinciding with the early follicular, late follicular, and mid-luteal phases ot their menstrual cycle. Muscle soreness, countermovement jump, creatine kinase (CK), myoglobin, lactate dehydrogenase, interleukin-6, tumor necrosis factor-α, and C-reactive protein were evaluated before and postexercise. RESULTS: The expected differences in sex hormones were observed between groups (P < 0.001) according to their reproductive status. Postexercise increases in CK, myoglobin, and muscle soreness (168.2 ± 45.5 U/L, 123.1 ± 41.5 µg/L, and 20.7 ± 21.3 mm, respectively) were observed in comparison with baseline (136.2 ± 45.5 U/L, 76.9 ± 13.8 µg/L, and 2.7 ± 4.2 mm, respectively). Myoglobin values at baseline in postmenopausal women were higher compared with premenopausal women in the aforementioned menstrual cycle phases, respectively (62.8 ± 8.2, 60.4 ± 7.2, and 60.1 ± 10.6 µg/L; P < 0.001 for all comparisons), which was supported by large effect sizes (0.72-1.08 standardized d units). No postexercise differences were observed between groups in any markers (P > 0.05). CONCLUSION: Despite higher resting levels of myoglobin and lower strength values in postmenopausal than in premenopausal women, EIMD was similar between both reproductive profiles. This suggests a potential benefit of being physically active despite aging and sex hormone deprivation. CLINICAL RELEVANCE: Sex hormone deprivation derived from menopause seems not to influence muscle damage reponse to eccentric exercise in resistance-trained postmenopausal women.

Bone mineral density in well-trained females with different hormonal profiles / Densidad mineral ósea en mujeres entrenadas con diferente perfil hormonal

Objective: The association between sex hormones and bone mineral density (BMD) has been studied in sedentary women,whereas only few studies have evaluated trained females. Therefore, the aim of this study was to assess the influence of sexhormones on BMD in well-trained females with different hormonal profiles: eumenorrheic females, oral contraceptive (OC)users and postmenopausal women. The secondary purpose was to determine if maximal oxygen consumption (V̇ O2max) ormaximal back squat strength (1RM) could be good predictors of BMD in this population. Methods: Sixty-eight eumenorrheic, forty-one monophasic-OC users and sixteen postmenopausal well-trained femalesparticipated in this study. A Dual-energy X-ray Absorptiometry scan (DXA), a basal blood sample and a maximal back squatand/or a maximal treadmill test were performed. In order to measure all volunteers under similar hormonal conditions (lowsex hormone levels), all tests were carried out during the early follicular phase for the eumenorrheic females and in thewithdrawal phase for the OC group. Results: One way ANCOVA reported lower values of BMD in postmenopausal (1.13±0.07g/cm2) than in eumenorrheic(1.19±0.08 g/cm2) (p=0.003) and OC users (1.17±0.07 g/cm2) (p=0.030). Pearson ́s correlation showed a positive relationshipbetween BMD and 1RM (p<0.001), but not with V̇ O2max.Conclusions: Lower BMD has been reported in postmenopausal women compared to both, eumenorrheic females and OCusers. BMD loss after menopause seems to be not fully compensated by exercise, but this could effectively mitigate it. Moreover,1RM back squat reported a slight association to BMD. Hence, strength training may be the best choice to prevent BMD loss.(AU)

Objetivo: La asociación entre hormonas sexuales y densidad mineral ósea (DMO) ha sido bastante estudiada en mujeressedentarias, pero no en mujeres entrenadas. Por tanto, el objetivo de este estudio fue analizar la influencia de las hormonassexuales en la DMO de deportistas con diferentes perfiles hormonales: mujeres eumenorreicas, usuarias de la píldora anti-conceptiva y mujeres postmenopáusicas. El segundo objetivo fue analizar si el consumo máximo de oxígeno (V̇ O2max) o lasentadilla trasera (1RM) serían buenos predictores de DMO en dicha población. Metodología: Sesenta y seis mujeres eumenorreicas, cuarenta y una usuaria de píldora monofásica y dieciséis mujerespostmenopáusicas bien entrenadas participaron en el estudio. Una densitometría ósea (DXA), una analítica basal y una prue-ba de esfuerzo y/o de 1RM en sentadilla trasera fueron llevados a cabo. Con el objetivo de que todas las voluntarias fueranmedidas bajo las mismas condiciones (bajos niveles de hormonas sexuales), todas las pruebas fueron realizadas en la fasefolicular temprana para las mujeres eumenorreicas y en la fase no hormonal para las usuarias de píldora. Resultados: ANCOVA de una vía mostró valores de DMO más bajos en mujeres postmenopáusicas (1,13±0,07g/cm2) compa-rado con las eumenorreicas (1,19±0,08 g/cm2) (p=0,003) y las usuarias de píldora (1,17±0,07 g/cm2) (p=0,030). La correlaciónde Pearson mostró una relación positiva entre DMO y sentadilla (p<0,001), pero no mostró asociación con el V̇ O2max. Conclusión: Las mujeres postmenopáusicas presentan valores de DMO más bajo que las mujeres eumenorreicas y las usuariasde píldora. El descenso de DMO tras la menopausia parece no ser completamente compensado por la práctica de actividadfísica, aunque ésta puede atenuar ese descenso. Además, la sentadilla mostró una ligera asociación positiva con la DMO, porlo que el entrenamiento de fuerza podría ser la mejor opción para prevenir el descenso de DMO.(AU)

Methodological Approach of the Iron and Muscular Damage: Female Metabolism and Menstrual Cycle during Exercise Project (IronFEMME Study).

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.

Menstrual Cycle Phases Influence on Cardiorespiratory Response to Exercise in Endurance-Trained Females.

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.

Cardiorespiratory response to exercise in endurance-trained premenopausal and postmenopausal females.

PURPOSE: To assess the influence of different hormonal profiles on the cardiorespiratory response to exercise in endurance-trained females. METHODS: Forty-seven eumenorrheic females, 38 low-dose monophasic oral contraceptive (OC) users and 13 postmenopausal women, all of them endurance-trained, participated in this study. A DXA scan, blood sample tests and a maximal aerobic test were performed under similar low-sex hormone levels: early follicular phase for the eumenorrheic females; withdrawal phase for the OC group and at any time for postmenopausal women. Cardiorespiratory variables were measured at resting and throughout the maximal aerobic test (ventilatory threshold 1, 2 and peak values). Heart rate (HR) was continuously monitored with a 12-lead ECG. Blood pressure (BP) was measured with an auscultatory method and a calibrated mercury sphygmomanometer. Expired gases were measured breath-by-breath with the gas analyser Jaeger Oxycon Pro. RESULTS: One-way ANCOVA reported a lower peak HR in postmenopausal women (172.4 ± 11.7 bpm) than in eumenorrheic females (180.9 ± 10.6 bpm) (p = 0.024). In addition, postmenopausal women exhibited lower VO2 (39.1 ± 4.9 ml/kg/min) compared to eumenorrheic females (45.1 ± 4.4 ml/kg/min) in ventilatory threshold 2 (p = 0.009). Nonetheless, respiratory variables did not show differences between groups at peak values. Finally, no differences between OC users and eumenorrheic females' cardiorespiratory response were observed in endurance-trained females. CONCLUSIONS: Cardiorespiratory system is impaired in postmenopausal women due to physiological changes caused by age and sex hormones' decrement. Although these alterations appear not to be fully compensated by exercise, endurance training could effectively mitigate them. In addition, monophasic OC pills appear not to impact cardiorespiratory response to an incremental running test in endurance-trained females.

The Effect of the Oral Contraceptive Cycle Phase on Exercise-Induced Muscle Damage After Eccentric Exercise in Resistance-Trained Women.

ABSTRACT: Romero-Parra, N, Rael, B, Alfaro-Magallanes, VM, Janse de Jonge, X, Cupeiro, R, and Peinado, AB; On Behalf of the IronFEMME Study Group. The effect of the oral contraceptive cycle phase on exercise-induced muscle damage after eccentric exercise in resistance-trained women. J Strength Cond Res 35(2): 353-359, 2021-To evaluate the influence of the active pill phase versus withdrawal phase of a monophasic oral contraceptive (OC) cycle on exercise-induced muscle damage and inflammation after eccentric resistance exercise. Eighteen resistance-trained female OC users (age: 25.6 ± 4.2 years, height: 162.4 ± 5.0 cm, and body mass: 58.1 ± 5.7 kg) performed an eccentric squat-based exercise during the active pill phase and withdrawal phase of their OC cycle. Muscle soreness, counter movement jump (CMJ), and blood markers of muscle damage and inflammation were evaluated before and postexercise (0, 2, 24, and 48 hours). Creatine kinase (CK) values were higher in the withdrawal (181.8 ± 89.8 U·L-1) than in the active pill phase (144.0 ± 39.7 U·L-1) (p < 0.001). The highest CK concentrations and muscle soreness values were observed 24 hours postexercise (217.9 ± 117.5 U·L-1 and 44.7 ± 19.7, respectively) compared with baseline (115.3 ± 37.4 U·L-1 and 4.4 ± 9.2, respectively; p < 0.001). In addition, a decrease in CMJ immediately postexercise (20.23 ± 4.6 cm) was observed in comparison with baseline (24.2 ± 6.1 cm), which was not yet recovered 24 hours postexercise (21.9 ± 5.9 cm; p < 0.001). No other phase or time effects were observed. An eccentric squat-based exercise session elicits muscle damage but no inflammation response in resistance-trained women. Furthermore, the highest CK concentrations observed in the withdrawal phase suggest that this phase might be more vulnerable to muscle damage and, therefore, less adequate to administer high training loads. However, the lack of differences in other muscle damage variables between OC phases does not warrant any guidance on the active pill versus withdrawal phase.

Body Composition Over the Menstrual and Oral Contraceptive Cycle in Trained Females.

PURPOSE: The influence of female sex hormones on body fluid regulation and metabolism homeostasis has been widely studied. However, it remains unclear whether hormone fluctuations throughout the menstrual cycle (MC) and with oral contraceptive (OC) use affect body composition (BC). Thus, the aim of this study was to investigate BC over the MC and OC cycle in well-trained females. METHODS: A total of 52 eumenorrheic and 33 monophasic OC-taking well-trained females participated in this study. Several BC variables were measured through bioelectrical impedance analysis 3 times in the eumenorrheic group (early follicular phase, late follicular phase, and midluteal phase) and on 2 occasions in the OC group (withdrawal phase and active pill phase). RESULTS: Mixed linear model tests reported no significant differences in the BC variables (body weight, body mass index, basal metabolism, fat mass, fat-free mass, and total body water) between the MC phases or between the OC phases (P > .05 for all comparisons). Trivial and small effect sizes were found for all BC variables when comparing the MC phases in eumenorrheic females, as well as for the OC cycle phases. CONCLUSIONS: According to the results, sex hormone fluctuations throughout the menstrual and OC cycle do not influence BC variables measured by bioelectrical impedance in well-trained females. Therefore, it seems that bioimpedance analysis can be conducted at any moment of the cycle, both for eumenorrheic women and women using OC.

Indirect Markers of Muscle Damage Throughout the Menstrual Cycle.

CONTEXT: The indirect markers of muscle damage have been previously studied in females. However, inconclusive results have been found, possibly explained by the heterogeneity regarding monitoring and verification of menstrual-cycle phase. PURPOSE: To determine whether the fluctuations in sex hormones during the menstrual cycle influence muscle damage. METHODS: A total of 19 well-trained eumenorrheic women (age 28.6 [5.9] y; height 163.4 [6.1] cm; weight 59.6 [5.8] kg body mass) performed an eccentric-based resistance protocol consisting of 10 × 10 back squats at 60% of their 1-repetition maximum on the early follicular phase (EFP), late follicular phase, and midluteal phase of the menstrual cycle. Range of motion, muscle soreness, countermovement jump, and limb circumferences were evaluated prior to 24 and 48 hours postexercise. Perceived exertion was evaluated after each set. RESULTS: Differences in sex hormones indicated that tests were adequately performed in the different menstrual-cycle phases. Prior to exercise, muscle soreness was higher in the EFP (4.7 [7.7]) than in the late follicular phase (1.1 [3.2]; P = .045). No other variables showed significant differences between phases. Time-point differences (baseline, 24, and 48 h) were observed in knee range of motion (P = .02), muscle soreness, countermovement jump, and between sets for perceived exertion (P < .001). CONCLUSION: Although the protocol elicited muscle damage, hormonal fluctuations over the menstrual cycle did not seem to affect indirect markers of muscle damage, except for perceived muscle soreness. Muscle soreness was perceived to be more severe before exercise performed in EFP, when estrogen concentrations are relatively low. This may impair women's predisposition to perform strenuous exercise during EFP.

Exercise-Induced Muscle Damage During the Menstrual Cycle: A Systematic Review and Meta-Analysis.

ABSTRACT: 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.

Menopause Delays the Typical Recovery of Pre-Exercise Hepcidin Levels after High-Intensity Interval Running Exercise in Endurance-Trained Women.

Menopause commonly presents the gradual accumulation of iron in the body over the years, which is a risk factor for diseases such as cancer, osteoporosis, or cardiovascular diseases. Running exercise is known to acutely increase hepcidin levels, which reduces iron absorption and recycling. As this fact has not been studied in postmenopausal women, this study investigated the hepcidin response to running exercise in this population. Thirteen endurance-trained postmenopausal women (age: 51.5 ± 3.89 years; height: 161.8 ± 4.9 cm; body mass: 55.9 ± 3.6 kg; body fat: 24.7 ± 4.2%; peak oxygen consumption: 42.4 ± 4.0 mL·min-1·kg-1) performed a high-intensity interval running protocol, which consisted of 8 × 3 min bouts at 85% of the maximal aerobic speed with 90-second recovery. Blood samples were collected pre-exercise, 0, 3, and 24 hours post-exercise. As expected, hepcidin exhibited higher values at 3 hours post-exercise (3.69 ± 3.38 nmol/L), but also at 24 hours post-exercise (3.25 ± 3.61 nmol/L), in comparison with pre-exercise (1.77 ± 1.74 nmol/L; p = 0.023 and p = 0.020, respectively) and 0 hour post-exercise (2.05 ± 2.00 nmol/L; p = 0.021 and p = 0.032, respectively) concentrations. These differences were preceded by a significant increment of interleukin-6 at 0 hour post-exercise (3.41 ± 1.60 pg/mL) compared to pre-exercise (1.65 ± 0.48 pg/m, p = 0.003), 3 hours (1.50 ± 0.00 pg/mL, p = 0.002) and 24 hours post-exercise (1.52 ± 0.07 pg/mL, p = 0.001). Hepcidin peaked at 3 hours post-exercise as the literature described for premenopausal women but does not seem to be fully recovered to pre-exercise levels within 24 hours post-exercise, as it would be expected. This suggests a slower recovery of basal hepcidin levels in postmenopausal women, suggesting interesting applications in order to modify iron homeostasis as appropriate, such as the prevention of iron accumulation or proper timing of iron supplementation.