Auditing the representation of hormonal contraceptives in studies assessing exercise performance in women.

Hormonal contraceptive (HC) users have a different ovarian hormonal profile compared to eumenorrheic women. Due to the prevalence of HC use amongst sportswomen, there has been increased research efforts to understand their impact on exercise performance. The aim was to audit this research. Studies identified were assessed for HC type, athlete calibre, performance outcome, study design, and quality of methodological control regarding ovarian hormonal profiles. Sixty-eight different HCs were reported across 61 studies. Monophasic combined oral contraceptive (OCP) pills represented 60% of HCs, followed by other pills [34%, phasic-combined, progestogen-only, and un-specified], phasic and long acting reversible contraceptives [5%, vaginal ring, patch, implant, injection, intrauterine system] and unspecified HCs (1%). Eleven percent of participants using HCs were classified as highly trained or elite/international with no participants being classed as world class. Whilst the number of studies involving HCs has increased two-fold over the past decade, the number of studies ranked as gold standard has not increased (HC; 2003-57%, 2011-55%, 2022-43%. OCP; 2003-14%, 2011-17%, 2022-12%). Future research assessing HCs and exercise performance should adopt high-quality research designs and include a broader range of HCs in highly trained to world-class populations to increase the reach and impact of research in this area.

Effect of Menstrual Cycle Phase and Hormonal Contraceptives on Resting Metabolic Rate and Body Composition.

The cyclical changes in sex hormones across the menstrual cycle (MC) are associated with various biological changes that may alter resting metabolic rate (RMR) and body composition estimates. Hormonal contraceptive (HC) use must also be considered given their impact on endogenous sex hormone concentrations and synchronous exogenous profiles. The purpose of this study was to determine if RMR and dual-energy X-ray absorptiometry body composition estimates change across the MC and differ compared with HC users. This was accomplished during a 5-week training camp involving naturally cycling athletes (n = 11) and HC users (n = 7 subdermal progestin implant, n = 4 combined monophasic oral contraceptive pill, n = 1 injection) from the National Rugby League Indigenous Women's Academy. MC phase was retrospectively confirmed via serum estradiol and progesterone concentrations and a positive ovulation test. HC users had serum estradiol and progesterone concentrations assessed at the time point of testing. Results were analyzed using general linear mixed model. There was no effect of MC phase on absolute RMR (p = .877), relative RMR (p = .957), or dual-energy X-ray absorptiometry body composition estimates (p > .05). There was no effect of HC use on absolute RMR (p = .069), relative RMR (p = .679), or fat mass estimates (p = .766), but HC users had a greater fat-free mass and lean body mass than naturally cycling athletes (p = .028). Our findings suggest that RMR and dual-energy X-ray absorptiometry body composition estimates do not significantly differ due to changes in sex hormones in a group of athletes, and measurements can be compared between MC phases or with HC usage without variations in sex hormones causing additional noise.

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 ß-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 ß-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.

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.

Female athlete health domains: a supplement to the International Olympic Committee consensus statement on methods for recording and reporting epidemiological data on injury and illness in sport.

The IOC made recommendations for recording and reporting epidemiological data on injuries and illness in sports in 2020, but with little, if any, focus on female athletes. Therefore, the aims of this supplement to the IOC consensus statement are to (i) propose a taxonomy for categorisation of female athlete health problems across the lifespan; (ii) make recommendations for data capture to inform consistent recording and reporting of symptoms, injuries, illnesses and other health outcomes in sports injury epidemiology and (iii) make recommendations for specifications when applying the Strengthening the Reporting of Observational Studies in Epidemiology-Sport Injury and Illness Surveillance (STROBE-SIIS) to female athlete health data.In May 2021, five researchers and clinicians with expertise in sports medicine, epidemiology and female athlete health convened to form a consensus working group, which identified key themes. Twenty additional experts were invited and an iterative process involving all authors was then used to extend the IOC consensus statement, to include issues which affect female athletes.Ten domains of female health for categorising health problems according to biological, life stage or environmental factors that affect females in sport were identified: menstrual and gynaecological health; preconception and assisted reproduction; pregnancy; postpartum; menopause; breast health; pelvic floor health; breast feeding, parenting and caregiving; mental health and sport environments.This paper extends the IOC consensus statement to include 10 domains of female health, which may affect female athletes across the lifespan, from adolescence through young adulthood, to mid-age and older age. Our recommendations for data capture relating to female athlete population characteristics, and injuries, illnesses and other health consequences, will improve the quality of epidemiological studies, to inform better injury and illness prevention strategies.

Female Athlete Representation and Dietary Control Methods Among Studies Assessing Chronic Carbohydrate Approaches to Support Training.

The aim of this audit was to assess the representation of female athletes, dietary control methods, and gold standard female methodology that underpins the current guidelines for chronic carbohydrate (CHO) intake strategies for athlete daily training diets. Using a standardized audit, 281 studies were identified that examined high versus moderate CHO, periodized CHO availability, and/or low CHO, high fat diets. There were 3,735 total participants across these studies with only ∼16% of participants being women. Few studies utilized a design that specifically considered females, with only 16 studies (∼6%) including a female-only cohort and six studies (∼2%) with a sex-based comparison in their statistical procedure, in comparison to the 217 studies (∼77%) including a male-only cohort. Most studies (∼72%) did not provide sufficient information to define the menstrual status of participants, and of the 18 studies that did, optimal methodology for control of ovarian hormones was only noted in one study. While ∼40% of male-only studies provided all food and beverages to participants, only ∼20% of studies with a female-specific design used this approach for dietary control. Most studies did not implement strategies to ensure compliance to dietary interventions and/or control energy intake during dietary interventions. The literature that has contributed to the current guidelines for daily CHO intake is lacking in research that is specific to, or adequately addresses, the female athlete. Redressing this imbalance is of high priority to ensure that the female athlete receives evidence-based recommendations that consider her specific needs.

Menstrual Cycle Related Fluctuations in Circulating Markers of Bone Metabolism at Rest and in Response to Running in Eumenorrheic Females.

This study examined potential fluctuations in bone metabolic markers across the menstrual cycle both at rest and after a 30-min bout of continuous running at 80% of V̇O2max. Resting and post-exercise (0, 30, 90 min) sclerostin, parathyroid hormone (PTH), carboxy-terminal cross-linking telopeptide of type I collagen (ß-CTXI), and procollagen type 1 N propeptide (PINP) were assessed in 10 eumenorrheic women (age: 21 ± 3 y, BMI: 23.2 ± 3.0 kg.m2) during the mid- to late-follicular (FP: day 8.0 ± 1.4) and mid-luteal (LP: day 22.0 ± 2.5) phases of the menstrual cycle. Ovulation was determined using ovulation kits and daily measurement of oral body temperature upon awakening. Menstrual cycle phase was subsequently confirmed by measurement of plasma estradiol and progesterone. On average, resting estradiol concentrations increased from 46.3 ± 8.9 pg·mL-1 in the FP to 67.3 ± 23.4 pg·mL-1 in the LP (p = 0.015), and resting progesterone increased from 4.12 ± 2.36 ng·mL-1 in the FP to 11.86 ± 4.49 ng·mL-1 in the LP (p < 0.001). At rest, there were no differences between menstrual cycle phases in sclerostin (FP: 260.1 ± 135.0 pg·mL-1; LP: 303.5 ± 99.9 pg·mL-1; p = 0.765), PTH (FP: 0.96 ± 0.64 pmol·L-1; LP: 0.79 ± 0.44 pmol·L-1; p = 0.568), ß-CTXI (FP: 243.1 ± 158.0 ng·L-1; LP: 202.4 ± 92.3 ng·L-1; p = 0.198), and PINP (FP: 53.6 ± 8.9 µg·L-1; LP: 66.2 ± 20.2 µg·L-1; p = 0.093). Main effects for time (p < 0.05) were shown in sclerostin, PTH, ß-CTXI and PINP, without phase or interaction effects. Sclerostin increased from pre- to immediately post-exercise (45%; p = 0.007), and so did PTH (43%; p = 0.011), both returning to resting concentrations 30 min post-exercise. ß-CTXI decreased from pre- to post-exercise (20%; p = 0.027) and was still below its pre-exercise concentrations at 90 min post-exercise (17%; p = 0.013). PINP increased immediately post-exercise (29%; p < 0.001), returning to resting concentrations at 30 min post-exercise. These results demonstrate no effect of menstrual cycle phase on resting bone marker concentrations or on the bone metabolic marker response to intense exercise.

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.

Methodology Review: A Protocol to Audit the Representation of Female Athletes in Sports Science and Sports Medicine Research.

Female-specific research on sports science and sports medicine (SSSM) fails to mirror the increase in participation and popularity of women's sport. Females have historically been excluded from SSSM research, particularly because their physiological intricacy necessitates more complex study designs, longer research times, and additional costs. Consequently, most SSSM practices are based on research with men, despite potential problems in translation to females due to sexual dimorphism in biological and phenotypical parameters as well as differences in event characteristics (e.g., race distances/durations). Recognition that erroneous extrapolations may hamper the efforts of females to maximize their athletic potential has created an impetus to acknowledge and readdress the sex disparity in SSSM research. To direct the priorities for future research, it is prudent to first develop a comprehensive understanding of the gaps in current knowledge by systematically "auditing" the literature. By conducting audits of the literature to highlight underdeveloped topics or identify potential problems with the quality of research, this information can then be used to expediently direct new research activities. This paper therefore presents a standardized audit methodology to establish the representation of female athletes in subdisciplines of existing SSSM research, including a template for reporting the results of key metrics. This standardized audit process will enable comparisons over time and between research subdisciplines. This working guide provides an important step toward achieving sex equity across SSSM research, with the eventual goal of providing evidence-based recommendations specific to the female athlete.

Nutrition for Special Populations: Young, Female, and Masters Athletes.

Adolescent, female, and masters athletes have unique nutritional requirements as a consequence of undertaking daily training and competition in addition to the specific demands of age- and gender-related physiological changes. Dietary education and recommendations for these special population athletes require a focus on eating for long-term health, with special consideration given to "at-risk" dietary patterns and nutrients (e.g., sustained restricted eating, low calcium, vitamin D and/or iron intakes relative to requirements). Recent research highlighting strategies to address age-related changes in protein metabolism and the development of tools to assist in the management of Relative Energy Deficiency in Sport are of particular relevance to special population athletes. Whenever possible, special population athletes should be encouraged to meet their nutrient needs by the consumption of whole foods rather than supplements. The recommendation of dietary supplements (particularly to young athletes) overemphasizes their ability to manipulate performance in comparison with other training/dietary strategies.

A Narrative Review on Female Physique Athletes: The Physiological and Psychological Implications of Weight Management Practices.

Physique competitions are events in which aesthetic appearance and posing ability are valued above physical performance. Female physique athletes are required to possess high lean body mass and extremely low fat mass in competition. As such, extended periods of reduced energy intake and intensive training regimens are used with acute weight loss practices at the end of the precompetition phase. This represents an increased risk for chronic low energy availability and associated symptoms of relative energy deficiency in sport, compromising both psychological and physiological health. Available literature suggests that a large proportion of female physique athletes report menstrual irregularities (e.g., amenorrhea and oligomenorrhea), which are unlikely to normalize immediately postcompetition. Furthermore, the tendency to reduce intakes of numerous essential micronutrients is prominent among those using restrictive eating patterns. Following competition, reduced resting metabolic rate, and hyperphagia, is also a concern for these female athletes, which can result in frequent weight cycling, distorted body image, and disordered eating/eating disorders. Overall, female physique athletes are an understudied population, and the need for more robust studies to detect low energy availability and associated health effects is warranted. This narrative review aims to define the natural female physique athlete, explore some of the physiological and psychological implications of weight management practices experienced by female physique athletes, and propose future research directions.

Reduced energy availability: implications for bone health in physically active populations.

PURPOSE: The present review critically evaluates existing literature on the effects of short- and long-term low energy availability (EA) on bone metabolism and health in physically active individuals. METHODS: We reviewed the literature on the short-term effects of low EA on markers of bone metabolism and the long-term effects of low EA on outcomes relating to bone health (bone mass, microarchitecture and strength, bone metabolic markers and stress fracture injury risk) in physically active individuals. RESULTS: Available evidence indicates that short-term low EA may increase markers of bone resorption and decrease markers of bone formation in physically active women. Bone metabolic marker responses to low EA are less well known in physically active men. Cross-sectional studies investigating the effects of long-term low EA suggest that physically active individuals who have low EA present with lower bone mass, altered bone metabolism (favouring bone resorption), reduced bone strength and increased risk for stress fracture injuries. CONCLUSIONS: Reduced EA has a negative influence on bone in both the short- and long-term, and every effort should be made to reduce its occurrence in physically active individuals. Future interventions are needed to explore the effects of long-term reduced EA on bone health outcomes, while short-term low EA studies are also required to give insight into the pathophysiology of bone alterations.

Endocrine Effects of Relative Energy Deficiency in Sport.

The term Relative Energy Deficiency in Sport was introduced by the International Olympic Committee in 2014. It refers to the potential health and performance consequences of inadequate energy for sport, emphasizing that there are consequences of low energy availability (EA; typically defined as <30 kcal·kg-1 fat-free mass·day-1) beyond the important and well-established female athlete triad, and that low EA affects populations other than women. As the prevalence and consequences of Relative Energy Deficiency in Sport become more apparent, it is important to understand the current knowledge of the hormonal changes that occur with decreased EA. This paper highlights endocrine changes that have been observed in female and male athletes with low EA. Where studies are not available in athletes, results of studies in low EA states, such as anorexia nervosa, are included. Dietary intake/appetite-regulating hormones, insulin and other glucose-regulating hormones, growth hormone and insulin-like growth factor 1, thyroid hormones, cortisol, and gonadal hormones are all discussed. The effects of low EA on body composition, metabolic rate, and bone in female and male athletes are presented, and we identify future directions to address knowledge gaps specific to athletes.

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.

Waking Up to the Issue! Research Inattention and Sex-Related Differences Warrant More Sleep Studies in Female Athletes.

Understanding sleep patterns and behaviors of athletes is essential for developing targeted sleep-based interventions for implementation in practice. However, more than double the number of sleep studies have examined male athletes compared with female athletes, making the current understanding of sleep patterns, behaviors, and interventions among athletes disproportionately indicative of men. Consequently, this review demonstrates the need for more female-specific sleep data among athlete populations due to research inattention and sex-related differences. Specifically, this review identifies variations in sleep patterns and behaviors between male and female athletes, as well as physiological and lifestyle factors that potentially affect sleep patterns and behaviors across the lifespan, specifically in female athletes. In this regard, evidence suggests some female athletes experience longer sleep durations and better objective sleep quality, but similar or worse subjective sleep quality compared with male athletes. Additionally, scheduling training in the morning or throughout the day may benefit sleep in some female athletes. Considering sleep disorders, women may be at greater risk for insomnia and restless legs syndrome compared with men, which may be attributed to pregnancy, as well as a higher prevalence of anxiety and depressive symptoms, iron deficiency without anemia, and use of psychotropic medication among women. Finally, the menstrual cycle, menstrual disorders, oral contraceptive use, and the postpartum period have been shown to exert detrimental effects on sleep patterns and behaviors and should theoretically be considered when monitoring and managing sleep in female athletes.

A reproducible, self-reported, field-based tool for monitoring ovarian hormone status and body weight variations in female athletes: the Answ'Her questionnaire.

BACKGROUND: Intra-individual factors like ovarian hormone profiles and body weight variations may influence sports practice and performance in female athletes and need to be characterized. The "Answ'Her" questionnaire was designed to develop a relevant and reproducible field-based tool to assess self-reported ovarian hormone status (natural menstrual cycle and hormonal contraceptive use) and body weight variations practices among female athletes. METHODS: French females with a regular sports practice responded (once: N.=210; twice: N.=86; thrice: N.=66) to this 73-item questionnaire reporting their ovarian hormone status, associated symptoms, perceived influence on sports practice, and body weight variations. Reproducibility was evaluated, then a descriptive cross-sectional analysis was conducted on athletes. RESULTS: Reproducibility was verified with 92% of Lin's correlation concordance coefficients above 0.7 and 100% of weighted agreements above 70%. Ultimately 185 female athletes (23.0±4.8 years) were included in the cross-sectional analysis. Whether they used hormonal contraceptive (46.5%) or not (53.5%), most of the athletes perceived a negative impact of their ovarian hormone status on sports practice (78.7%) and performance (84.7%). Overall, 77.3% of the athletes had experienced body weight variations that were significantly associated with an interruption of menses (>3 months) and menses irregularity over the last three years. CONCLUSIONS: The Answ'Her questionnaire is a simple and effective reproducible field-based tool for the self-reported characterisation of female athlete ovarian hormone status and body weight variations. It could be used for a unique and simple overview of the athlete situation but also in a longitudinal design to assess the athlete's evolution and/or effectiveness of implanted training strategies.

Minimal influence of the menstrual cycle or hormonal contraceptives on performance in female rugby league athletes.

We examined performance across one menstrual cycle (MC) and 3 weeks of hormonal contraceptives (HC) use to identify whether known fluctuations in estrogen and progesterone/progestin are associated with functional performance changes. National Rugby League Indigenous Women's Academy athletes [n = 11 naturally menstruating (NM), n = 13 using HC] completed performance tests [countermovement jump (CMJ), squat jump (SJ), isometric mid-thigh pull, 20 m sprint, power pass and Stroop test] during three phases of a MC or three weeks of HC usage, confirmed through ovulation tests alongside serum estrogen and progesterone concentrations. MC phase or HC use did not influence jump height, peak force, sprint time, distance thrown or Stroop effect. However, there were small variations in kinetic and kinematic CMJ/SJ outputs. NM athletes produced greater mean concentric power in MC phase four than one [+0.41 W·kg-1 (+16.8%), p = 0.021] during the CMJ, alongside greater impulse at 50 ms at phase one than four [+1.7 N·s (+4.7%), p = 0.031] during the SJ, without differences between tests for HC users. Among NM athletes, estradiol negatively correlated with mean velocity and power (r = -0.44 to -0.50, p < 0.047), progesterone positively correlated with contraction time (r = 0.45, p = 0.045), and both negatively correlated with the rate of force development and impulse (r = -0.45 to -0.64, p < 0.043) during the SJ. During the CMJ, estradiol positively correlated to 200 ms impulse (r = 0.45, p = 0.049) and progesterone to mean power (r = 0.51, p = 0.021). Evidence of changes in testing performance across a MC, or during active HC use, is insufficient to justify "phase-based testing"; however, kinetic or kinematic outputs may be altered in NM athletes.

Prevalence of hormonal contraceptive use and reported side effects of the menstrual cycle and hormonal contraceptive use in powerlifting and rugby.

OBJECTIVES: The prevalence of hormonal contraceptive (HC) use and the associated symptomology of use or nonuse are under-studied in athletic populations, and in particular, in strength and collision sports. This study aimed to investigate the prevalence of hormonal contraceptive use and reported side effects of the menstrual cycle and hormonal contraceptive use in powerlifters and rugby players. METHODS: Competitive female powerlifters and rugby players (aged ≥18 y), representing a strength and a collision sport respectively, completed an anonymous online questionnaire for the purpose of assessing self-reported prevalence of HC use, and symptoms of the menstrual cycle and HC use. Athletes were categorized by sport (powerlifters, n = 149; rugby players, n = 135) in order to conduct a stratified analysis. For open-ended questions, a content analysis was conducted to categorize responses, and frequency analyses were performed. RESULTS: Current HC use was reported by 51.1% of athletes, with similar prevalence for the two sports (powerlifting, 48.3% vs. rugby, 54.1%, P = 0.34). Side effects of the menstrual cycle were reported in 83.5% of non-HC users, with the most common being unspecified cramping (42.4%), headache/migraine (24.5%), and fatigue (24.5%). Side effects were reported in 40.0% of HC users, with the most common being mood changes (17.9%), stomach pain (8.3%) and headaches/migraines (6.9%). CONCLUSION: A large proportion of HC users and nonusers in this study experience negative side effects of HC use and the menstrual cycle, respectively. The symptoms experienced by both groups are wide-ranging, with a high degree of variation between individuals. The negative side-effects experienced by HC users and nonusers may have an influence on athletic performance, and this requires future investigation.

Comparative analysis of bone outcomes between quantitative ultrasound and dual-energy x-ray absorptiometry from the UK Biobank cohort.

This large cohort study investigated reliability and validity of heel ultrasound to estimate bone mineral density in adults. Reliability calculated between left and right heels was relatively poor and so was criterion validity assessed relative to dual-energy X-ray absorptiometry. Heel ultrasound should be used cautiously when estimating bone mineral density. INTRODUCTION: Calcaneal quantitative ultrasound (QUS) may be used as a safe, low cost, and portable means to estimate bone mineral density (BMD) in large cohorts. The purpose of this study was to quantify the reliability and validity of QUS in comparison to dual-energy X-ray absorptiometry (DXA), which is the reference method for BMD measurement and diagnoses of osteopenia and osteoporosis. METHODS: Bone outcomes measured on the large UK Biobank cohort were used. The reliability of QUS estimated BMD was quantified by comparing values obtained from the left and right heel measured in the same session. Criterion validity was assessed through agreement between QUS and DXA, quantifying correlations, and sensitivity and specificity of osteopenia and osteoporosis diagnoses. RESULTS: Reliability calculations were made using data from over 216,000 participants demonstrating similar QUS BMD values between left and right heels in the absolute scale (Sd of difference for men: 0.12 and 0.07 g·cm-2). However, when expressed in relative scales, including concordance of quartiles, reliability was poor. Agreement between QUS and DXA was quantified using data from 5042 participants. Low to modest correlations (r = 0.29 to 0.44) were obtained between multiple QUS variables and DXA BMD, with sensitivity identified as very poor (0.05 to 0.23) for osteoporosis, and poor (0.37 to 0.62) for osteopenia diagnoses. CONCLUSIONS: The findings of this large comparative analysis identify that whilst calcaneal QUS has the potential to produce reliable absolute BMD measurements and demonstrate modest associations with DXA BMD measures, use of that information to make relative statements about participants in the context of the larger population or to appropriately diagnose osteopenia or osteoporosis may be severely limited.