Female physiology–endocrinology: education is lacking and innovation is needed!

Throughout their lifespans, women undergo unique endocrinological changes relative to their reproductive hormones. The influence of how the female sex steroid hormones have nonreproductive actions is a trending topic of great interest in the exercise–sports sciences, especially among women of reproductive age. Herein, we present several key points on our perspective for moving the study of this topic forward in the future. These are (a) encouraging researchers to pursue high-quality research on female physiology–endocrinology in the exercise–sports science setting, (b) the need for exercise–sports science educational curriculums at the university level to embrace the study of female physiology–endocrinology area, and (c) the need for innovation in the study of this topic. As such, we propose using research design models involving supraphysiological hormonal states in vivo, that is, pregnancy and in vitro fertilization treatment, to gain new insights on sex steroid hormonal actions in women. Herein, we provide the rationale for our recommendations as well as a brief physiological overview of these clinical states. We acknowledge, exercise sports sciences need more studies on women! But there is a need to “think outside the box” on this topic, and we encourage researchers to be unconventional, be bold, think creatively, and contemplate whether these supraphysiological hormonal states might give them insightful information on female physiology and ovarian sex steroid hormones actions

Experiences of physical activity, healthy eating and quality of life during and following pregnancy in overweight and obese postpartum women

Objectives This retrospective study explored the experiences of women with overweight or obesity regarding physical activity, diet and quality of life leading up to, during, and following pregnancy. Methods A qualitative descriptive design was adopted, whereby data collected through semi-structured interviews were analysed using thematic analysis. Throughout the interviews, individuals were asked to describe their barriers to a healthy lifestyle during and following pregnancy. Results Ten women (34.5 ± 5.2 years old, BMI 30.4 ± 3.5 kg·m− 2) who were between 12 and 52 weeks postpartum participated. A range of themes were identified when discussing barriers to physical activity and healthy eating during and following pregnancy. For example, tiredness, especially in the third trimester of pregnancy, and a lack of support at home, was often cited as preventing engagement in exercise and healthy eating practices. A lack of convenience when attending exercise classes, medical complications following the birth and the cost of attending pregnancy-specific classes were identified as barriers to exercise engagement. Cravings and nausea were identified as barriers to healthy eating during pregnancy. Quality of life was positively associated with exercise and healthy eating, whilst a lack of sleep, loneliness and a loss of freedom since the baby had arrived negatively influenced quality of life. Discussion Postpartum women with overweight and obesity experience many barriers when attempting to engage in a healthy lifestyle during and following pregnancy. These findings can be used to inform the design and delivery of future lifestyle interventions in this population. Significance What is Already Known on this Subject? Pregnant and postpartum women experience a multitude of barriers when attempting to engage in a healthy lifestyle. What this Study adds? Until now, investigations into barriers to participation in a healthy lifestyle in overweight and obese pregnant and postpartum women have been lacking. Akin to normal weight women, women with a BMI > 25 kg/m2 experience many barriers to a healthy lifestyle during and following pregnancy. In this exclusive overweight and obese population, medical complications was the most cited barrier to postpartum exercise engagement. These results will be considered when designing future postpartum lifestyle interventions

Influence of menstrual cycle and oral contraceptive phases on bone (re)modelling markers in response to interval running

To explore how sex hormone fluctuations may affect bone metabolism, this study aimed to examine P1NP and β-CTX-1 concentrations across the menstrual and oral contraceptive (OC) cycle phases in response to running. 17β-oestradiol, progesterone, P1NP and β-CTX-1 were analysed pre- and post-exercise in eight eumenorrheic females in the early-follicular, late-follicular, and mid-luteal phases, while 8 OC users were evaluated during the withdrawal and active pill-taking phases. The running protocol consisted of 8 × 3min treadmill runs at 85% of maximal aerobic speed. 17β-oestradiol concentrations (pg·ml−1) were lower in early-follicular (47.22 ± 39.75) compared to late-follicular (304.95 ± 235.85;p = < 0.001) and mid-luteal phase (165.56 ± 80.6;p = 0.003) and higher in withdrawal (46.51 ± 44.09) compared to active pill-taking phase (10.88 ± 11.24;p < 0.001). Progesterone (ng·ml−1) was higher in mid-luteal (13.214 ± 4.926) compared to early-follicular (0.521 ± 0.365; p < 0.001) and late-follicular phase (1.677 ± 2.586;p < 0.001). In eumenorrheic females, P1NP concentrations (ng·ml−1) were higher in late-follicular (69.97 ± 17.84) compared to early-follicular (60.96 ± 16.64;p = 0.006;) and mid-luteal phase (59.122 ± 11.77;p = 0.002). β-CTX-1 concentrations (ng·ml−1) were lower in mid-luteal (0.376 ± 0.098) compared to late-follicular (0.496 ± 0.166; p = 0.001) and early-follicular phase (0.452 ± 0.148; p = 0.039). OC users showed higher post-exercise P1NP concentrations in withdrawal phase (61.75 ± 8.32) compared to post-exercise in active pill-taking phase (45.45 ± 6;p < 0.001). Comparing hormonal profiles, post-exercise P1NP concentrations were higher in early-follicular (66.91 ± 16.26;p < 0.001), late-follicular (80.66 ± 16.35;p < 0.001) and mid-luteal phases (64.57 ± 9.68;p = 0.002) to active pill-taking phase. These findings underscore the importance of studying exercising females with different ovarian hormone profiles, as changes in sex hormone concentrations affect bone metabolism in response to running, showing a higher post-exercise P1NP concentrations in all menstrual cycle phases compared with active pill-taking phase of the OC cycle

P1NP and β-CTX-1 responses to a prolonged, continuous running bout in young healthy adult males: a systematic review with individual participant data meta-analysis.

Circulating biomarkers of bone formation and resorption are widely used in exercise metabolism research, but their responses to exercise are not clear. To quantify group responses and inter-individual variability of P1NP and β-CTX-1 after prolonged, continuous running (60-120 min at 65-75% VO2max) in young healthy adult males using individual participant data (IPD) meta-analysis. The protocol was designed following PRISMA-IPD guidelines. Changes in P1NP and β-CTX-1 relative to baseline were measured during, immediately after, and in the hours and days following exercise. Typical hourly and daily variations were estimated from P1NP and β-CTX-1 changes relative to baseline in non-exercise (control) conditions. Group responses and inter-individual variability were quantified with estimates of the mean and standard deviation of the difference, and the proportion of participants exhibiting an increased response. Models were conducted within a Bayesian framework with random intercepts to account for systematic variation across studies. P1NP levels increased during and immediately after running, where the proportion of response was close to 100% (75% CrI: 99 to 100%). P1NP levels returned to baseline levels within 1 hour and over the next 4 days, showing comparable mean and standard deviation of the difference with typical hourly (0.1 ± 7.6 ng·ml-1) and daily (-0.4 ± 5.7 ng·ml-1) variation values. β-CTX-1 levels decreased during and up to 4 hours after running with distributions comparable to typical hourly variation (-0.13 ± 0.11 ng·ml-1). There was no evidence of changes in β-CTX-1 levels during the 4 days after the running bout, where distributions were also similar between the running data and typical daily variation and (-0.03 ± 0.10 ng·ml-1). Transient increases in P1NP were likely biological artefacts (e.g., connective tissue leakage) and not reflective of bone formation. Comparable small decreases in β-CTX-1 identified in both control and running data, suggested that these changes were due to the markers' circadian rhythm and not the running intervention. Hence, prolonged continuous treadmill running did not elicit bone responses, as determined by P1NP and β-CTX-1, in this population. The protocol for this review was pre-registered on the Open Science Framework prior to implementation (https://osf.io/y69nd)

Carnosine increases insulin-stimulated glucose uptake and reduces methylglyoxal-modified proteins in type-2 diabetic human skeletal muscle cells

Type-2 diabetes (T2D) is characterised by a dysregulation of metabolism, including skeletal muscle insulin resistance, mitochondrial dysfunction, and oxidative stress. Reactive species, such as methylglyoxal (MGO) and 4-hydroxynonenal (4-HNE), positively associate with T2D disease severity and can directly interfere with insulin signalling and glucose uptake in skeletal muscle by modifying cellular proteins. The multifunctional dipeptide carnosine, and its rate-limiting precursor β-alanine, have recently been shown to improve glycaemic control in humans and rodents with diabetes. However, the precise mechanisms are unclear and research in human skeletal muscle is limited. Herein, we present novel findings in primary human T2D and lean healthy control (LHC) skeletal muscle cells. Cells were differentiated to myotubes, and treated with 10 mM carnosine, 10 mM β-alanine, or control for 4-days. T2D cells had reduced ATP-linked and maximal respiration compared with LHC cells (p = 0.016 and p = 0.005). Treatment with 10 mM carnosine significantly increased insulin-stimulated glucose uptake in T2D cells (p = 0.047); with no effect in LHC cells. Insulin-stimulation increased MGO-modified proteins in T2D cells by 47%; treatment with carnosine attenuated this increase to 9.7% (p = 0.011). There was no effect treatment on cell viability or expression of other proteins. These findings suggest that the beneficial effects of carnosine on glycaemic control may be explained by its scavenging actions in human skeletal muscle

Feminae: an international multi-site innovative project for female athletes.

Sufficient high-quality studies in sport science using women as participants are lacking, meaning that our knowledge and understanding of female athletes in relation to their ovarian hormone profiles is limited. Consortia can be used to pool talent, expertise, and data, thus accelerating our learning on a given topic and reducing research waste through collaboration. To this end, we have assembled an international multi-site team, described herein, to investigate the effects of the menstrual cycle and oral contraceptive pill phase on aspects of exercise physiology and sports performance in female athletes. We intend to produce an adequately powered, high-quality dataset which can be used to inform the practices of female athletes. Our approach will also employ research transparency – through the inclusion of a process evaluation - and reproducibility – through a standardised study protocol

The legacy of pregnancy: elite athletes and women in arduous occupations

Best-practice guidance and management of pregnant and postpartum elite athletes and women in arduous occupations is limited by the lack of high-quality evidence available within these populations. We have summarized the adaptations and implications of pregnancy and childbirth, proposed a novel integrative concept to address these changes, and made recommendations to progress research in this area

The symptoms experienced by naturally menstruating women and oral contraceptive pill users and their perceived effects on exercise performance and recovery time posttraining

This study examined the type, frequency, and severity of symptoms experienced by naturally menstruating women and combined, monophasic, oral contraceptive pill users and their perceived effects on exercise performance and recovery time posttraining. Forty-two recreationally active women; 21 naturally menstruating and 21 combined, monophasic, oral contraceptive pill users participated in the study. Data were collected using two approaches: (a) an online 54-part retrospective survey and (b) a daily questionnaire. “Total number of symptoms,” “symptom index score,” “average symptom severity,” and “symptom index × severity score” were calculated from the retrospective data set. Real-time symptom data (i.e., “symptom frequency per phase” and “phase symptom frequency × severity score”) were calculated across predefined cycle phases from the daily questionnaire. The retrospective survey showed that symptoms were commonly reported by recreationally active women, but there were no differences in symptomology between the groups (p >.113). The daily questionnaire showed both groups experienced a greater frequency and severity of symptoms while bleeding (p ≤.001), which was associated with perceived reductions in exercise performance (odds ratio = 1.04–1.07) and a perceived longer recovery time posttraining (odds ratio = 1.03– 1.04). The results from this study show that cycle-related symptoms were commonly reported by a group of recreationally active women, with no difference in symptomology between naturally menstruating women and combined, monophasic, oral contraceptive pill users. The magnitude of symptoms was greater while bleeding, which was associated with a perceived reduction in exercise performance and a longer recovery time posttraining

β-alanine supplementation to improve exercise capacity and performance: a systematic review and meta-analysis.

Objective To conduct a systematic review and meta-Analysis of the evidence on the effects of β-Alanine supplementation on exercise capacity and performance. Design This study was designed in accordance with PRISMA guidelines. A 3-level mixed effects model was employed to model effect sizes and account for dependencies within data. Data sources 3 databases (PubMed, Google Scholar, Web of Science) were searched using a number of terms (b € β-Alanine' and b € Beta-Alanine' combined with b € supplementation', b € exercise', b € training', b € athlete', b € performance' and b € carnosine'). Eligibility criteria for selecting studies Inclusion/exclusion criteria limited articles to double-blinded, placebo-controlled studies investigating the effects of β-Alanine supplementation on an exercise measure. All healthy participant populations were considered, while supplementation protocols were restricted to chronic ingestion. Cross-over designs were excluded due to the long washout period for skeletal muscle carnosine following supplementation. A single outcome measure was extracted for each exercise protocol and converted to effect sizes for meta-Analyses. Results 40 individual studies employing 65 different exercise protocols and totalling 70 exercise measures in 1461 participants were included in the analyses. A significant overall effect size of 0.18 (95% CI 0.08 to 0.28) was shown. Meta-regression demonstrated that exercise duration significantly (p=0.004) moderated effect sizes. Subgroup analyses also identified the type of exercise as a significant (p=0.013) moderator of effect sizes within an exercise time frame of 0.5-10b €.min with greater effect sizes for exercise capacity (0.4998 (95% CI 0.246 to 0.753)) versus performance (0.1078 (95% CI b '0.201 to 0.416)). There was no moderating effect of training status (p=0.559), intermittent or continuous exercise (p=0.436) or total amount of β-Alanine ingested (p=0.438). Co-supplementation with sodium bicarbonate resulted in the largest effect size when compared with placebo (0.43 (95% CI 0.22 to 0.64)). Summary/conclusions β-Alanine had a significant overall effect while subgroup analyses revealed a number of modifying factors. These data allow individuals to make informed decisions as to the likelihood of an ergogenic effect with β-Alanine supplementation based on their chosen exercise modality

Current evidence shows no influence of women's menstrual cycle phase on acute strength performance or adaptations to resistance exercise training

Introduction: The bias towards excluding women from exercise science research is often due to the assumption that cyclical fluctuations in reproductive hormones influence resistance exercise performance and exercise-induced adaptations. Methods: Hence, the purpose of this umbrella review was to examine and critically evaluate the evidence from meta-analyses and systematic reviews on the influence of menstrual cycle phase on acute performance and chronic adaptations to resistance exercise training (RET). Results: We observed highly variable findings among the published reviews on the ostensible effects of female sex hormones on relevant RET-induced outcomes, including strength, exercise performance, and hypertrophy. Discussion: We highlight the importance of comprehensive menstrual cycle verification methods, as we noted a pattern of poor and inconsistent methodological practices in the literature. In our opinion, it is premature to conclude that short-term fluctuations in reproductive hormones appreciably influence acute exercise performance or longer-term strength or hypertrophic adaptations to RET