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.

Menstrual cycle affects iron homeostasis and hepcidin following interval running exercise in endurance-trained women.

PURPOSE: Menstrual cycle phase affects resting hepcidin levels, but such effects on the hepcidin response to exercise are still unclear. Thus, we investigated the hepcidin response to running during three different menstrual cycle phases. METHODS: Twenty-one endurance-trained eumenorrheic women performed three identical interval running protocols during the early-follicular phase (EFP), late-follicular phase (LFP), and mid-luteal phase (MLP). The protocol consisted of 8 × 3 min bouts at 85% of the maximal aerobic speed, with 90-s recovery. Blood samples were collected pre-exercise and at 0 h, 3 h and 24 h post-exercise. RESULTS: Data presented as mean ± SD. Ferritin were lower in the EFP than the LFP (34.82 ± 16.44 vs 40.90 ± 23.91 ng/ml, p = 0.003), while iron and transferrin saturation were lower during the EFP (58.04 ± 19.70 µg/dl, 14.71 ± 5.47%) compared to the LFP (88.67 ± 36.38 µg/dl, 22.22 ± 9.54%; p < 0.001) and the MLP (80.20 ± 42.05 µg/dl, 19.87 ± 10.37%; p = 0.024 and p = 0.045, respectively). Hepcidin was not affected by menstrual cycle (p = 0.052) or menstrual cycle*time interaction (p = 0.075). However, when comparing hepcidin at 3 h post-exercise, a moderate and meaningful effect size showed that hepcidin was higher in the LFP compared to the EFP (3.01 ± 4.16 vs 1.26 ± 1.25 nMol/l; d = 0.57, CI = 0.07-1.08). No effect of time on hepcidin during the EFP was found either (p = 0.426). CONCLUSION: The decrease in iron, ferritin and TSAT levels during the EFP may mislead the determination of iron status in eumenorrheic athletes. However, although the hepcidin response to exercise appears to be reduced in the EFP, it shows no clear differences between the phases of the menstrual cycle (clinicaltrials.gov: NCT04458662).

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.

The acute effect of the menstrual cycle and oral contraceptive cycle on measures of body composition.

PURPOSE: This study aimed to investigate the effect of fluctuating female hormones during the menstrual cycle (MC) and oral contraceptive (OC) cycle on different measures of body composition. METHODS: Twenty-two women with a natural MC and thirty women currently taking combined monophasic OC were assessed over three phases of the menstrual or oral contraceptive cycle. Body weight, skinfolds, bioelectric impedance analysis (BIA), ultrasound, dual-energy X-ray absorptiometry (DXA), and peripheral quantitative computed tomography (pQCT) measurements were performed to assess body composition. Urine specific gravity (USG) was measured as an indication of hydration, and serum oestradiol and progesterone were measured to confirm cycle phases. RESULTS: Five participants with a natural MC were excluded based on the hormone analysis. For the remaining participants, no significant changes over the MC and OC cycle were found for body weight, USG, skinfolds, BIA, ultrasound and pQCT measures. However, DXA body fat percentage and fat mass were lower in the late follicular phase compared to the mid-luteal phase of the MC, while for the OC cycle, DXA body fat percentage was higher and lean mass lower in the early hormone phase compared with the late hormone phase. CONCLUSION: Our findings suggest that assessment of body fat percentage through BIA and skinfolds may be performed without considering the MC or OC cycle. Body adiposity assessment via DXA, however, may be affected by female hormone fluctuations and therefore, it may be advisable to perform repeat testing using DXA during the same phase of the MC or OC cycle.

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.

Ferritin status impact on hepcidin response to endurance exercise in physically active women along different phases of the menstrual cycle / Impacto de las reservas de ferritina sobre la respuesta de la hepcidina al ejercicio de resistencia en las mujeres físicamente activas a lo largo de las diferentes fases del ciclo menstrual

Serum ferritin has been proposed as a predictor of hepcidin concentrations in response to exercise. However, this fact has not been studied in physically-active women. Therefore, the main objective of this study was to analyse the hepcidin response at different ferritin status before and after running exercise in physically active females. Fifteen eumenorrheic women performed a 40-min running protocol at 75% of VO2peak speed in different menstrual cycle phases (early-follicular phase, mid-follicular phase and luteal phase). Blood samples were collected pre-exercise, 0h post-exercise and 3h post-exercise. For statistics, participants were divided into two groups according to their pre-exercise ferritin levels (< 20 and ≥ 20 μg/L). Through menstrual cycle, hepcidin was lower in both early follicular phase (p = 0.024; 64.81 ± 22.48 ng/ml) and mid-follicular phase (p = 0.007; 64.68 ± 23.91 ng/ml) for < 20 μg/L ferritin group, in comparison with ≥20 μg/L group (81.17 ± 27.89 and 79.54 ± 22.72 ng/ml, respectively). Hepcidin showed no differences between both ferritin groups in either pre-exercise, 0h post-exercise and 3h post-exercise. Additionally, no association between pre-exercise ferritin and hepcidin levels 3 h post-exercise (r = -0.091; p = 0.554) was found. Menstrual cycle phase appears to influence hepcidin levels depending on ferritin reserves. In particular, physically-active females with depleted ferritin reserves seems to present lower hepcidin levels during the early-follicular phase and mid-follicular phase. However, no association between ferritin and hepcidin levels was found in this study. Hence, ferritin levels alone may not be a good predictor of hepcidin response to exercise in this population. Multiple factors such as sexual hormones, training loads and menstrual bleeding must be taken into account

La ferritina sérica parece ser un predictor de la respuesta de la hepcidina al ejercicio. Sin embargo, este hecho no ha sido estudiado en mujeres físicamente activas. El objetivo fue analizar la respuesta de la hepcidina en diferentes estados de la ferritina antes y después del ejercicio. Quince mujeres eumenorreicas realizaron un protocolo de carrera de 40 minutos al 75% de la velocidad VO2pico en diferentes fases del ciclo menstrual (fase folicular temprana, fase folicular media y fase lútea). Se recogieron muestras de sangre antes del ejercicio y a las 0h y 3h después del ejercicio. Las participantes se dividieron en dos grupos según sus niveles de ferritina previos al ejercicio (< 20 y ≥ 20 μg/L). La hepcidina fue más baja tanto en la fase folicular temprana (p = 0,024; 64,81 ± 22,48 ng/ml) como en las fase folicular media (p = 0,007; 64,68 ± 23,91 ng/ml) para el grupo de ferritina < 20 μg/L en comparación con el grupo de ferritina ≥ 20 μg/L (81,17 ± 27,89 y 79,54 ± 22,72 ng/ml, respectivamen-te). La hepcidina no mostró diferencias entre ambos grupos de ferritina para ninguno de los momentos (antes del ejercicio ejercicio, 0h y 3h después del ejercicio). No se encontró ninguna asociación entre los niveles de ferritina previos al ejercicio y los niveles de hepcidina 3h posteriores al ejercicio (r = -0,091; p = 0,554). El ciclo menstrual parece influir en los niveles de hepcidina dependiendo de las reservas de ferritina. En particular, las mujeres físicamente activas con reservas de ferritina agotadas parecen presentar niveles de hepcidina más bajos durante la fase folicular temprana y la fase folicular media. Sin embargo, no se encontró ninguna asociación entre la ferritina y la hepcidina. Por lo tanto, los niveles de ferritina por sí solos pueden no ser un buen predictor de la respuesta de la hepcidina al ejercicio en esta población. Se deben tener en cuenta múltiples factores como las hormonas sexuales, las cargas de entrenamiento y el sangrado menstrual

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.

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.

Hepcidin response to interval running exercise is not affected by oral contraceptive phase in endurance-trained women.

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 17ß-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 17ß-estradiol concentrations during the active pill phase but did not affect hepcidin. This does not, however, rule out estradiol affecting hepcidin levels.

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.

Systemic iron homeostasis in female athletes: hepcidin, exercise and sex influence / Homeostasis sistémica del hierro en mujeres deportistas: hepcidina, ejercicio y la influencia del sexo

Iron is necessary for adequate deliver oxygen to the tissues since it is an essential component of the haemoglobin. However, iron deficiency remains a common problem among athletes, particularly for women experiencing the menstrual bleeding every month. The iron losses through menstrual blood loss during the early follicular phase (or menses) and an inadequate dietary intake of iron are two important factors contributing to this disease. Furthermore, the large hormonal changes that women experience along the menstrual cycle, especially in oestrogen and progesterone may influence on the optimization of iron absorption. Iron absorption is mainly mediated by hepcidin hormone, which seems to be affected by several stimulus and factors such as oestrogen and progesterone concentrations. Moreover, the regular practice of exercise is another important modulator of this hormone. Therefore, premenopausal active females are the most susceptible population to develop an iron deficiency or iron deficiency anemia, affecting their health and performance due to the less iron availability within the body and consequently a reduction of haemoglobin which compromise the oxygen transport. To date, most studies have not explored the acute post-exercise hepcidin response taking endogenous and exogenous sexual hormones influence into account. This narrative review will focus on how iron homeostasis is modulated by different factors mainly influenced by exercise and female sexual hormones

El hierro es necesario para suministrar adecuadamente el oxígeno a los tejidos, ya que es un componente esencial de la hemoglobina. Sin embargo, la deficiencia de hierro sigue siendo un problema común entre los atletas, particularmente para las mujeres que experimentan el sangrado menstrual cada mes. Las pérdidas de hierro producidas tras la el sangrado menstrual durante la fase folicular temprana (o menstruación), además de una ingesta dietética inadecuada de hierro son dos factores importantes que contribuyen a esta enfermedad. Además, los grandes cambios hormonales que experimentan las mujeres a lo largo del ciclo menstrual, especialmente en el estrógeno y la progesterona, pueden influir en la optimización de la absorción de hierro. La absorción de hierro está mediada principalmente por la hormona hepcidina, que parece verse afectada por varios estímulos y factores como las concentraciones de estrógeno y progesterona. Además, la práctica regular de ejercicio es otro importante modulador de esta hormona. Por lo tanto, las mujeres activas premenopáusicas son la población más susceptible de desarrollar una deficiencia de hierro o anemia ferropénica, lo que afecta a su salud y rendimiento debido a la menor disponibilidad de hierro en el cuerpo y en consecuencia, a la reducción de la hemoglobina que compromete el transporte de oxígeno. Hasta la fecha, la mayoría de los estudios no han explorado la respuesta aguda de la hepcidina después del ejercicio teniendo en cuenta la influencia de las hormonas sexuales endógenas y exógenas.E sta revisión narrativa se centrará en cómo la homeostasis del hierro es modulada por diferentes factores influenciados principalmente por el ejercicio y las hormonas sexuales femeninas

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-, 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.

Elevated hepcidin serum level in response to inflammatory and iron signals in exercising athletes is independent of moderate supplementation with vitamin C and E.

Iron deficiency among endurance athletes is of major concern for coaches, physicians, and nutritionists. Recently, it has been observed that hepcidin, the master regulator of iron metabolism, was upregulated after exercise and was found to be related to interleukin-6 (IL-6) elevation. In this study performed on noniron deficient and well-trained runners, we observed that hepcidin concentrations remain elevated in response to inflammatory and iron signals despite a 28-days supplementation period with vitamins C (500 mg/day) and E (400 IU/day).