Dear Editor,

Hamilton et al (1) conducted a study to assess strength, power and aerobic capacity of transgender athletes. They conclude the results may be useful for sports governing bodies and inform sports policy. However, policy should be informed by accurate scientific information and, unfortunately, this study contains fundamental errors in design, methodology and interpretation. In this letter, we focus on the incorrect interpretation of respiratory testing, the inappropriate definition of ‘athlete’, and group matching.

The study compares respiratory function of transgender and non-transgender individuals using cardiopulmonary exercise testing, as well as conventional lung function testing (spirometry, lung volumes and gas transfer). The authors report that transgender women (TW - male individuals who identify as women) had greater forced expiratory volume in 1s (FEV1), forced vital capacity (FVC) and peak expiratory flow rate (PEFR) and a reduced FEV1/FVC ratio relative to cisgender women (CW - female individuals without a differing gender identity). From this data, the authors conclude that TW have decreased lung function, increasing their work of breathing relative to CW.

Firstly, the methodology employed to measure lung function does not appear to conform to accepted, published testing guidelines (ATS/ERS) (2). Lung function is typically measured repeatedly within 150mL, with the highest numeric value for each variable recorded, to ensure reproducible high-quality measures, and not until a ‘declining performance occurred’. Secondly, in the TW group, data was included from an individual with abnormal findings (FEV/FVC ratio of approximately 0.62), indicating an individual with probable obstructive airways disease (3,4), confounding interpretation of mean data. Thirdly, the authors fail to correct lung function data for factors known to influence these variables, in addition to sex, e.g. height, ethnicity and age (5,6). In this study, the TW group are older and taller, and male, and as such, would be expected to have a lower FEV1/FVC relative to CW. When the published mean values are considered relative to these factors and compared with internationally validated Global Lung Initiative (GLI) reference ranges, the FEV1/FVC values are within normal ranges for corresponding predicted values in all groups (including the TW). Within these normal ranges, these results do not reflect reduced lung function in the TW, as a group, and do not represent an increased challenge to the ‘work of breathing’ as presented and discussed in this paper (6,7). The reported difference of FEV1/FVC, 0.88 (CW) vs. 0.83 (TW), arises because CW have a disproportionately lower FVC, as is normal for female and shorter individuals. This difference is further exacerbated by the inclusion of one individual with probable pathological airflow obstruction in the TW group. The study also reports that TW have a higher FEV1, FVC and PEFR relative to CW and therefore, if hypothesising on exercise performance based on absolute respiratory test values, it would be appropriate to discuss that TW may have improved lung function for sports performance (8), precisely the opposite conclusion drawn by the authors.

Methodologically, there is also a significant grouping error. The stated primary aim was to ‘compare cardiorespiratory fitness, strength and body composition of transgender athletes to that of matched cisgender cohorts’. Yet groups in this study were not matched, with clear differences in height, body mass index, fat mass index, and relative V ̇O2 max, between TW and CW. The TW group have the highest BMI (26.2kg/m2), Fat Mass Index (8.2 kg/m2) and Fat Mass (31.5%) and lowest V ̇O2 Max (45.1ml/kg/min) of any group in the study. These values are not physiologically representative of an athlete cohort (9). The study defines participants as athletes based on self-reported participation in a sport (unspecified) or in any physical training (unspecified) at least 3-times per week. This is not aligned with study guidelines on the definition of an ‘athlete’ (10). The authors suggest their study should influence sporting governing bodies and athletic sports policy, providing ‘sports governing bodies with laboratory-based performance related data from transgender athletes’. Neither the questionnaire-based criteria nor the physiological parameters are consistent with this being an athlete cohort.

In conclusion, we recommend the paper by Hamilton at al undergoes significant revision. The interpretation of respiratory testing is inaccurate and should include discussion on FEV1/FVC in the context of age, sex and height and relative to normative data. If the discussion on respiratory testing values and their possible impact on exercise performance is then retained, the potential for improved exercise performance of an increased FVC, FEV1 and PEFR in the TW group, relative to the CW group, should be discussed. Erroneous conclusions regarding ‘decreased lung function and increased work of breathing’ in TW should be removed. The study did not effectively match groups and the TW group do not meet published recommendations or physiological criteria to support an ‘athlete’ designation. Accordingly, we advise the study title is changed, the discussion, conclusions and ‘summary box’ corrected, and references to this as an athlete group removed. This is a contentious area of sports policy (11,12) and the British Journal of Sports Medicine should ensure that published scientific work draws credible conclusions and accurately informs readers.

References
1. Hamilton B, Brown A, Montagner-Moraes S, Comeras-Chueca C, Bush PG, Guppy FM, Pitsiladis YP. Strength, power and aerobic capacity of transgender athletes: a cross-sectional study. Br J Sports Med. 2024 Apr 10;bjsports-2023-108029.
2. Graham BL, Steenbruggen I, Miller MR, Barjaktarevic IZ, Cooper BG, Hall GL, et al. Standardization of Spirometry 2019 Update. An Official American Thoracic Society and European Respiratory Society Technical Statement. Am J Respir Crit Care Med. 2019 Oct 15;200(8):e70–88.
3. Singh D, Agusti A, Anzueto A, Barnes PJ, Bourbeau J, Celli BR, et al. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease: the GOLD science committee report 2019. Eur Respir J [Internet]. 2019 May 1 [cited 2024 May 31];53(5). Available from: https://erj.ersjournals.com/content/53/5/1900164
4. Recommendations | Asthma: diagnosis, monitoring and chronic asthma management | Guidance | NICE [Internet]. NICE; 2017 [cited 2024 May 31]. Available from: https://www.nice.org.uk/guidance/ng80/chapter/Recommendations#objective-...
5. Hankinson JL, Odencrantz JR, Fedan KB. Spirometric reference values from a sample of the general U.S. population. Am J Respir Crit Care Med. 1999 Jan;159(1):179–87.
6. Cooper BG, Stocks J, Hall GL, Culver B, Steenbruggen I, Carter KW, et al. The Global Lung Function Initiative (GLI) Network: bringing the world’s respiratory reference values together. Breathe. 2017 Sep;13(3):e56–64.
7. Haynes JM, Stumbo RW. The Impact of Using Non-Birth Sex on the Interpretation of Spirometry Data in Subjects With Air-Flow Obstruction. Respir Care. 2018 Feb;63(2):215–8.
8. McNeill J, Chernofsky A, Nayor M, Rahaghi FN, San Jose Estepar R, Washko G, et al. The association of lung function and pulmonary vasculature volume with cardiorespiratory fitness in the community. Eur Respir J. 2022 Aug;60(2):2101821.
9. Degens H, Stasiulis A, Skurvydas A, Statkeviciene B, Venckunas T. Physiological comparison between non-athletes, endurance, power and team athletes. Eur J Appl Physiol. 2019 Jun 1;119(6):1377–86.
10. McKinney J, Velghe J, Fee J, Isserow S, Drezner JA. Defining Athletes and Exercisers. Am J Cardiol. 2019 Feb 1;123(3):532–5.
11. IOC. IOC Framework on Fairness, Inclusion and Non-Discrimination on the basis of Gender Identity and Sex Variations [Internet]. IOC; 2021. Available from: https://stillmed.olympics.com/media/Documents/News/2021/11/IOC-Framework...
12. Lundberg TR, Tucker R, McGawley K, Williams AG, Millet GP, Sandbakk Ø, et al. The International Olympic Committee framework on fairness, inclusion and nondiscrimination on the basis of gender identity and sex variations does not protect fairness for female athletes. Scand J Med Sci Sports. 2024 Mar;34(3):e14581.

We thank Brown and O'Connor (1) for their interest in our research (2) and we welcome their constructive criticism, especially regarding our study design, analysis and interpretation. We consider such exchanges equally important as the dissemination of the original research and hence, we wish to address all concerns. Concerns were raised about the need for more specific inclusion criteria to ensure comparability among research participants. Specifically, Brown and O’Connor (1) raised valid concerns about the lack of detailed information on the frequency, intensity, duration, and mode of exercise among our research participants. While we appreciate and totally agree with these comments, the task of recruiting suitable research participants, mainly from small demographic groups such as transgender athletes, is challenging. Many transgender athletes, especially those with high profile, feel too intimidated to come forward in the current polarised climate. Given this, we had to balance the need for stringent inclusion criteria with the necessity of obtaining a representative sample of transgender athletes to better understand their physiological and performance characteristics. We aimed to strike a balance between providing an informative overview of the participants' sporting backgrounds and protecting the anonymity of the transgender athletes involved in the study. We fully acknowledge that a more granular breakdown would have been beneficial for assessing comparability among groups, and we recognise the value of more specific data and will continue to prioritise this in all our future research endeavours. Without a doubt, this balancing act, while essential for the advancement of knowledge in this field, will have contributed to some of the variability in training backgrounds among participants and may have influenced the findings of this research. For example, some of the differences between cisgender men, cisgender women and transgender women in terms of body composition, muscle strength, and aerobic fitness may be the result of variations in training backgrounds and the specifics of their chosen athletic pursuits. We attempted to reduce the impact of this important limitation by imposing the inclusion criteria of training three times per week and participating in competitive sport. Therefore, it can be inferred that all volunteers participating in our study were actively engaged in competitive sports, which would involve a variety of different training modalities. Given the status quo of almost no published data from transgender athletes, we opted to do the best we could in recruitment and design, appropriately analyse the data and present the findings while stressing the limitations of the research. As a result, our paper includes a detailed limitations section which addresses most of the concerns raised by Brown and O’Connor and others. For instance, in our limitations, we declared that the composition of the study cohort may not fully represent the diversity of athletes in elite sports from worldwide populations, and the study may suffer from selection bias (2, 3). While we acknowledge that this research we present is meant to encourage larger subject numbers and better methods in participant selection to improve the generalizability of research findings, there is a notable absence of studies that can establish an optimal sample size to determine whether transgender athletes possess unfair advantages. We acknowledged the limitations of our research but at the same time celebrate the uniqueness of our study and its strengths, which also include appropriate methods to assess the subjects’ strength, power and aerobic capacity, not to mention that all transgender participants have undergone years of hormonal treatment and have consistently maintained hormone levels within acceptable ranges; strengths that have received almost no attention. We believe that our research, despite its limitations, is a significant step towards better understanding the physiological and performance characteristics of transgender athletes, and we are committed to furthering this understanding through more collaborative research.

In response to the comment by Brown and O'Connor (1) that transgender women in our study exhibited a higher body fat percentage compared to comparably aged men (4) and previously researched non-athletic transgender women (5, 6), it is essential to consider the influence of hormonal factors, specifically in the case of Alvares, Santos (5), who did not report any oestradiol findings, and Scharff, Wiepjes (6), who reported oestradiol (Range 225-257 pmol·L-1). Transgender women in our present study had oestradiol concentrations sixfold higher (742 pmol·L-1) than those of cisgender men (104 pmol·L-1), double that of cisgender women (336. pmol·L-1) and threefold higher than was reported in Scharff, Wiepjes (6). Given that oestradiol is known to be positively associated with fat mass accumulation (7), it is unsurprising that transgender women athletes presented with higher fat mass levels. However, as our research is cross-sectional, we cannot establish that causation. The result of higher oestradiol concentrations may be caused by athletes self-medicating with gender-affirmation hormone treatment, as we did not recruit from a clinic, which means that the gender-affirming treatment of transgender athletes in our study (2) was not controlled. Longitudinal studies tracking transgender athletes over time are crucial to better understanding the relationship between hormone levels, body composition changes, and athletic performance. An important limitation of cross-sectional studies, as we declare in our study (2), is the inability to determine causality, making it impossible to determine whether the lower performances (e.g., relative maximal aerobic capacity) we report in transgender women athletes compared to cisgender women are due to gender-affirmation hormone treatment or simply due to a lower training status. Likewise, the higher absolute fat mass observed in transgender women athletes may be influenced by oestrogen therapy, which can lead to increases in both visceral and subcutaneous fat. Therefore, longitudinal studies are crucial to provide a more comprehensive understanding.

Our study, which focuses on physical performance aspects such as strength, power, and aerobic capacity, should serve as a primer to the broader discussion of gender inclusion, highlighting the importance of recognizing the differences between groups, especially between cisgender men and transgender women. There is also a call for a more comprehensive approach to research on sports performance across diverse sports, utilizing specific metrics to gain deeper insights into the priorities of each sport. Additionally, studies focusing on physiological aspects such as metabolic, hormonal, and biomarkers are essential to address questions like the residual effects of testosterone in relation to the "muscle memory mechanism" (8); the current focus of our research on this topic.

Unfortunately, the issue of integration of transgender athletes into elite sport has generated so much negative and polarised discussion that no matter what design is employed, subjects recruited, and intervention applied, no amount of research would change the entrenched position of those who are vehemently either pro- or anti-inclusion. In short, this issue is now political and only scientific data, with its acknowledged limitations, can best inform the debate, not that scientists themselves are immune from contributing to the politics of this debate. Below are some examples of the social media critiques our paper has received that were addressed in the limitations of our paper (2).

1) “19 transgender women, 20 cisgender women, 19 cisgender men and 11 transgender men. Such low numbers, even for an experimental or preliminary study, is laughable and can hardly be taken seriously.” (9)
2) “When I first read it, it made me think that the IOC and their researchers simply could not find enough transgender athletes to study over time, and so instead, they’ve just taken whatever they could find, and then compared to them a group of whatever females they could find, and tried to portray it as a valid comparison.” (10)
3) “This study has numerous problems, including self-selection of participants, wide variation in ages of the participants, and no control over hormone treatment of its transgender participants.” (10)
4) “If you read the baseline characteristics of the study groups you see that the trans athletes have a BMI in the overweight range while the women are lower BMI. Basically the research is comparing fat blokes with athletic women. This is not a serious piece of research and seems designed to confirm the IOC bias that men can compete in women’s events.” (9)
5) “These demographic characteristics should already make us pause – these groups may not be comparable for reasons that really matter. We have a group of females who are on the higher end of cardiovascular capacity along the female spectrum, and there is a group of transgender women in the middle of that range, even the lower side of it. One group is overweight, the other is not.” (10)

We encourage all who read our paper to pay particular attention to our declared limitations and engage with generating original data rather than dismissing the work of others. So heated is the debate on transgender inclusion that we have received threats and emails that are too vulgar to be presented and constitute abuse and, in some countries, a criminal offence. We hope that publication of original studies such as our imperfect study, will encourage better funded collaborative research in this area to keep the emphasis on science and not politics.
 
References
1. Gregory A Brown, Mary I O'Connor. Concerns with Strength, power and aerobic capacity of transgender athletes: a cross-sectional study. Published on: 3 May 2024 https://bjsm.bmj.com/content/early/2024/04/10/bjsports-2023-108029.respo...
2. Hamilton B, Brown A, Montagner-Moraes S, Comeras-Chueca C, Bush PG, Guppy FM, et al. Strength, power and aerobic capacity of transgender athletes: a cross-sectional study. British Journal of Sports Medicine. 2024.
3. Tripepi G, Jager KJ, Dekker FW, Zoccali C. Selection bias and information bias in clinical research. Nephron Clinical Practice. 2010;115(2):c94-c9.
4. Imboden MT, Welch WA, Swartz AM, Montoye AH, Finch HW, Harber MP, et al. Reference standards for body fat measures using GE dual-energy x-ray absorptiometry in Caucasian adults. PloS one. 2017;12(4):e0175110.
5. Alvares LAM, Santos MR, Souza FR, Santos LM, de Mendonça BB, Costa EMF, et al. Cardiopulmonary capacity and muscle strength in transgender women on long-term gender-affirming hormone therapy: a cross-sectional study. British journal of sports medicine. 2022;56(22):1292-9.
6. Scharff M, Wiepjes CM, Klaver M, Schreiner T, t’Sjoen G, Den Heijer M. Change in grip strength in trans people and its association with lean body mass and bone density. Endocrine connections. 2019;8(7):1020-8.
7. Al-Ghadban S, Teeler ML, Bunnell BA. Estrogen as a Contributing Factor to the Development of Lipedema. Hot Topics in Endocrinology and Metabolism: IntechOpen; 2021.
8. Pitsiladis Yannis, Harper JMS, Betancurt JO, Martinez-Patino MJ, Parisi A, Wang G, Pigozzi F. Beyond Fairness: The Biology of Inclusion for Transgender and Intersex Athletes. Current Sports Medicine Reports 15(6):p 386-388, 11/12 2016.
9. Dineen, Robert. "Transgender sportswomen 'at a disadvantage' study claims." The Telegraph, 11 April 2024, https://www.telegraph.co.uk/sport/2024/04/11/transgender-sportswomen-at-...
10. Ben Rumsby. “IOC accused of new low by funding study that claims trans women are at a disadvantage” The Telegraph, 12 April 2024, https://www.telegraph.co.uk/olympics/2024/04/12/ioc-accused-new-low-fund...

In responding to the comments raised in the letter to the editor regarding the recommendation of the VISA-G questionnaire for gluteal tendinopathy, we first want to acknowledge qualified agreement with the points raised while also emphasising the practical considerations and guidelines that informed our recommendation.

1. A key conclusion of our recent publication was that we were not able to form a Core Outcome Set as no outcome measure had sufficient clinimetric properties (1). For a measure to be selected for a Core Outcome Set, it should have at least high-quality evidence of good content validity (2 3). As part of the COS-GT consensus process, we completed a systematic review that collected and evaluated measurement properties of all outcome measures used to evaluate patients with gluteal tendinopathy. (4) No outcome measures met this threshold. Of the ICON disability domain outcome measures that had been validated in people with gluteal tendinopathy (the VISA-G and the two HOS outcome measures), the VISA-G had, albeit low, the best available evidence for content validity (low-quality evidence of sufficient comprehensibility and very low-quality evidence of sufficient comprehensiveness and relevance). (4) After much consideration the final recommendation for interim use was based on consideration of the impact of not providing a recommendation and the COSMIN systematic review guidelines for formulating recommendations. (p45, 4.2 Step 9) (5)

2. We acknowledge the limitation for the lack of uni-dimensionality of the VISA-G and the need to address this in future.

3. Please see point 1 as to why VISA-G was ultimately recommended. With respect to the reflexivity statements – we acknowledge that our reflexivity statements failed to reflect the steering committee’s discussion and concerns about the conflicting recommendations from patients and healthcare providers. Indeed, the full author group did wrestle with this question. Ultimately, it was decided on balance – and with consideration to the matters raised above in #1 – to recommend it rather than not.

As rightly pointed out by Thorborg et al rapid response, there is an urgent need for a new PROM that addresses the shortcomings of existing measures. In the absence of such a measure, our interim recommendation of the VISA-G aligns with COSMIN guidelines as the outcome measure with the best available content validity. (p45, 4.2 Step 9) (5) It's noteworthy that this pragmatic approach was endorsed by 100% of healthcare professionals in the consensus process. This approach addresses the immediate need for a measure for clinicians and researchers while acknowledging its deficiencies.

In conclusion, we agree that there is a pressing need for a new PROM for gluteal tendinopathy disability – as well as measures for other ICON tendinopathy domains for which measures in this condition do not exist. We remain committed to ongoing research and development aimed at addressing the limitations of existing PROMs in this field.

Sincerely,

The Author Team

References

1. Fearon AM, Grimaldi A, Mellor R, Nasser AM, Fitzpatrick J, Ladurner A, et al. ICON 2020-International Scientific Tendinopathy Symposium Consensus: the development of a core outcome set for gluteal tendinopathy. Br J Sports Med. 2024;58(5):245-54.
2. Terwee CB, Prinsen CAC, Chiarotto A, de Vet HCW, Bouter LM, Alonso J, et al. COSMIN methodology for assessing the content validity of PROMs User manual 2018 [Available from: https://www.cosmin.nl/tools/guideline-conducting-systematic-review-outco....
3. Terwee CB, Prinsen CAC, Chiarotto A, Westerman MJ, Patrick DL, Alonso J, et al. COSMIN methodology for evaluating the content validity of patient-reported outcome measures: a Delphi study. Qual Life Res. 2018;27(5):1159-70.
4. Nasser AM, Fearon AM, Grimaldi A, Vicenzino B, Mellor R, Spencer T, et al. Outcome measures in the management of gluteal tendinopathy: a systematic review of their measurement properties. Br J Sports Med. 2022;56(15):877-87.
5. Mokkink LB, Prinsen CAC, Patrick DL, Alonso J, Bouter LM, de Vet HCW, et al. COSMIN methodology for systematic reviews of
Patient‐Reported Outcome Measures (PROMs) 2018 [Available from: https://www.cosmin.nl/finding-right-tool/conducting-systematic-review-ou....