Influence of sex hormones on body composition and cardiorespiratory response to exercise in trained females: IronFEMME study = Influencia de las hormonas sexuales en la composición corporal y la respuesta cardiorrespiratoria al ejercicio en mujeres deportistas: Proyecto IronFEMME

Introducción: En los últimos años se ha producido un incremento de la participación femenina tanto en deportes de competición como en actividad física recreativa. Sin embargo, la gran mayoría de los estudios son realizados con hombres, mientras que las mujeres son excluidas porque su estudio conlleva una serie de dificultades metodológicas. Concretamente, los diferentes estados hormonales por los que pasa una mujer a lo largo de su vida deben ser tenidos en cuenta. Esto se debe a que hay receptores de hormonas sexuales en tejidos como el hipotálamo, el sistema cardiorrespiratorio, el músculo y el tejido adiposo, lo que puede afectar el rendimiento. Por tanto, es importante investigar la posible influencia de las hormonas sexuales femeninas en el ejercicio. Los objetivos de esta tesis fueron evaluar la influencia de las hormonas sexuales femeninas en la composición corporal y en la respuesta cardiorrespiratoria en ejercicio en mujeres deportistas, analizando no solo diferentes perfiles hormonales (mujeres eumenorreicas, usuarias de anticonceptivos orales (OC) y mujeres postmenopáusicas), sino también las diferentes fases del ciclo menstrual y del ciclo de OC. Por un lado, se ha estudiado la influencia de los distintos perfiles hormonales en la densidad mineral ósea (BMD) (Estudio I) y en la composición corporal (Estudio II). Además, la composición corporal también ha sido evaluada en las diferentes fases del ciclo menstrual: fase folicular temprana (EFP), fase folicular tardía (LFP) y fase lútea media (LFP), así como en las distintas fases del ciclo de OC: fase no hormonal (WP) y fase hormonal (APP) (Estudio III). Por otro lado, la respuesta cardiorrespiratoria en ejercicio ha sido analizada comparando los tres perfiles hormonales (Estudio IV), a lo largo del ciclo menstrual (EFP, LFP y MLP) (Estudio V), a lo largo del ciclo de OC (WP y APP) (Estudio VI) y en mujeres postmenopáusicas comparándola con la de las eumenorreicas (Estudio VII). Conclusiones: Las principales conclusiones obtenidas son las siguientes: Las mujeres postmenopáusicas presentan valores de BMD más bajos que las mujeres eumenorreicas y las usuarias de OC. Además, el uso de OC parece no afectar a la BMD de las mujeres deportistas (Estudio I). Con respecto a los diferentes perfiles hormonales, estos parecen no influir en la composición corporal de las mujeres activas (Estudio II). Por último, las fluctuaciones hormonales a lo largo del ciclo menstrual y del ciclo de OC no influyen en la composición corporal de las mujeres deportistas (Estudio III). Con respecto a la respuesta cardiorrespiratoria durante una prueba incremental, esta respuesta está ligeramente empeorada en las mujeres postmenopáusicas. Sin embargo, el uso de OC parece no influir en la respuesta cardiorrespiratoria durante un ejercicio de intensidad creciente en mujeres deportistas (Estudio IV). Además, las fluctuaciones de las hormonas sexuales a lo largo del ciclo menstrual parecen no ser suficientes como para modificar los ajustes llevados a cabo por el sistema cardiorrespiratorio para realizar un ejercicio de alta intensidad (Estudio V). Por otro lado, las deportistas usuarias de OC sufren un aumento de la Ve en la APP, acompañado de un aumento de la RPE, lo que debería tenerse en cuanta a la hora de programar los entrenamientos (Estudio VI). Finalmente, las mujeres postmenopáusicas presentan una menor respuesta cardiorrespiratoria en ejercicio interválico de alta intensidad que la de las mujeres eumenorreicas. Sin embargo, ambas presentan un trabajo cardíaco similar en valores relativos (Estudio VII). ----------ABSTRACT---------- Introduction: Female´s participation in sports and recreational physical activities has increased in the last few year. Nonetheless, most research in sport is conducted with males and females are often excluded due to methodological difficulties. Concretely, different reproductive status occurring in females´ live span have to be taken into consideration. This is because there are sex hormone receptors in several non-reproductive tissues such as the hypothalamus, cardiorespiratory system, skeletal muscle and adipose tissue, that may influence performance variables in this population. Thus, it is important to start focussing research on these potential effects of sex hormones on their sports activities. Therefore, the aims of this thesis were to assess sex hormones influence on body composition (BC) variables and cardiorespiratory response to exercise in well-trained females analyzing not only different hormonal profiles (eumenorrheic females, OC users and postmenopausal women) but also across the different phases of the natural menstrual cycle (MC) and monophasic oral contraceptive (OC) cycle. On the one hand, it has been studied the impact of the different hormonal profiles on bone mineral density (BMD) (Study I) and body composition (BC) (Study II). Besides, BC variables have also been evaluated throughout the different phases of the MC and OC cycle (Study III). On the other hand, cardiorespiratory response to exercise has been evaluated comparing the three different hormonal profiles (Study IV), over the MC (Study V), across the OC cycle (Study VI) and in postmenopausal women (Study VII). Conclusions: The main findings of this thesis are the following ones. Active postmenopausal women have a lower BMD compared to both, eumenorrheic females and OC users (Study I). With regard to BC, sex hormones seem not to influence these variables in active women neither when comparing different hormonal profiles (Study II) nor throughout the MC and OC cycle (Study III). Moving on to the cardiorespiratory response to exercise, postmenopausal women present a slightly lower response during an incremental running test compared to premenopausal females. However, monophasic OC pills appear not to impact cardiorespiratory response to exercise (Study IV). On the one hand, sex hormone fluctuations throughout the MC appear not to be high enough to disrupt cardiorespiratory adjustments caused by the high-intensity exercise (Study V). On the other hand, OC users experience a higher Ve and RPE during the APP, that should be considered in female´s training programs (Study VI). Finally, postmenopausal women have a lower cardiorespiratory response to high-intensity interval running protocol than eumenorrheic females. Nonetheless, cardiac strain is similar when comparing both groups in relative values (Study VII)

Influencia del ciclo menstrual y el uso de anticonceptivos orales en el rendimiento y la salud de la mujer deportista

Introducción: La influencia de las diferentes fases del ciclo menstrual en el rendimiento en mujeres deportistas no está clara. Además, pocos estudios han evaluado la relación que hay entre el uso de anticonceptivos orales y el rendimiento deportivo en mujeres. Por tanto, la finalidad de este trabajo fue realizar una valoración funcional a una mujer con regla regular (menstruación, folicular y lútea) y a una mujer usuaria de píldora anticonceptiva (hormonal y no hormonal) en las diferentes fases del ciclo menstrual. Además, otro objetivo ha sido proponer pautas de entrenamiento para cada una de estas mujeres que eviten la deficiencia de hierro. Métodos: Dos mujeres practicantes de deportes de resistencia (edad: 32 años) han participado en este trabajo, una de ellas con reglas regulares y la otra usuaria de anticonceptivos orales. En primer lugar realizaron una densitometría ósea y una prueba de esfuerzo, así como una analítica basal. Posteriormente, se realizaron fases estables en tapiz rodante al 75% del consumo de oxígeno máximo en cada una de las fases hormonales (mujer reglas regulares: folicular temprana, folicular tardía y lútea; mujer usuaria píldora anticonceptiva: fase hormonal y fase no- hormonal). Resultados: No hay grandes diferencias entre la fase lútea y la folicular, mientras que la fase menstrual presenta un nivel mas bajo de VO2 en el caso de nuestra voluntaria de reglas regulares. Por otro lado, la voluntaria usuaria de píldora muestra una VE ligeramente inferior en la fase no-hormonal. Conclusiones: Una vez realizadas las pruebas de valoración, podemos concluir que la voluntaria de regla regular presentó durante la folicular temprana una respuesta fisiológica inferior; mientras que la voluntaria usuaria de anticonceptivos orales mostró una respuesta fisiológica inferior durante la fase no-hormonal

Bone mineral density in well-trained females

Although the association between sex hormones and bone mineral density in healthy sedentary women has been widely studied (1,2), only a few studies have evaluated this relationship in trained females (3). Therefore, the purpose of this study was to assess the influence of sex hormones on BMD in physically active females: eumenorrheic females, oral contraceptive (OC) users and postmenopausal women. The secondary aim was to determine if maximal oxygen consumption (V ̇O2max) or maximal back squat strength (1RM) could be good predictors of BMD in this population

Bone mineral density in well-trained females

Although the association between sex hormones and bone mineral density in healthy sedentary women has been widely studied (1,2), only a few studies have evaluated this relationship in trained females (3). Therefore, the purpose of this study was to assess the influence of sex hormones on BMD in physically active females: eumenorrheic females, oral contraceptive (OC) users and postmenopausal women. The secondary aim was to determine if maximal oxygen consumption (V ̇O2max) or maximal back squat strength (1RM) could be good predictors of BMD in this population

Respiratory and perceived exertion variables during an intervallic endurance protocol through menstrual cycle phases

Respiratory variables, rating of perceived exertion (RPE) and perceived readiness (PR) can vary depending on the menstrual cycle phase due to the different sexual hormone environments found through it [1, 2]. Few studies compare more than 2 menstrual cycle phases and even fewer use intense intervallic endurance protocols [1, 2]. Additionally, oestrogen seems to have powerful effects in some exercise variables, although it may reduce muscle endurance capacity [3]. Therefore, the main objective of this study was to compare respiratory variables, RPE and PR measured in 3 phases of the menstrual cycle during an intervallic endurance protocol

Bone mineral density in well-trained females with different hormonal profiles

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 sex hormones 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 (V̇O2max) or maximal 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 females participated in this study. A Dual-energy X-ray Absorptiometry scan (DXA), a basal blood sample and a maximal back squat and/or a maximal treadmill test were performed. In order to measure all volunteers under similar hormonal conditions (low sex hormone levels), all tests were carried out during the early follicular phase for the eumenorrheic females and in the withdrawal 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 relationship between BMD and 1RM (p<0.001), but not with V̇O2max.Conclusions: Lower BMD has been reported in postmenopausal women compared to both, eumenorrheic females and OC users. 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. Objetivo: La asociación entre hormonas sexuales y densidad mineral ósea (DMO) ha sido bastante estudiada en mujeres sedentarias, pero no en mujeres entrenadas. Por tanto, el objetivo de este estudio fue analizar la influencia de las hormonas sexuales 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 (V̇O2max) o la sentadilla 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 mujeres postmenopáusicas 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 fueran medidas bajo las mismas condiciones (bajos niveles de hormonas sexuales), todas las pruebas fueron realizadas en la fase folicular 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 correlación de Pearson mostró una relación positiva entre DMO y sentadilla (p<0,001), pero no mostró asociación con elV̇O2max.Conclusión: Las mujeres postmenopáusicas presentan valores de DMO más bajo que las mujeres eumenorreicas y las usuarias de píldora. El descenso de DMO tras la menopausia parece no ser completamente compensado por la práctica de actividad física, aunque ésta puede atenuar ese descenso. Además, la sentadilla mostró una ligera asociación positiva con la DMO, por lo que el entrenamiento de fuerza podría ser la mejor opción para prevenir el descenso de DMO

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

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

Influence of the Menstrual Cycle on Blood Markers of Muscle Damage and Inflammation Following Eccentric Exercise

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

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