Singh and colleagues’ comprehensive systematic review of meta-analyses (97 reviews of 1039 trials including 128,119 participants) confirms that ‘physical activity (PA) is highly beneficial for improving symptoms of depression, anxiety and psychological distress’ with ‘effect size reductions in symptoms of depression (−0.43) and anxiety (−0.42) comparable to or slightly greater than those observed for psychotherapy and pharmacotherapy’.
This finding has important clinical implications and the authors conclude that PA should be included in public health guidelines as a mainstay approach (i.e. not just as an adjunct to psychological therapy and medication). They also recognise that ‘while the benefit of exercise for depression and anxiety is generally recognised, it is often overlooked in the management of these conditions’ .

Despite these really impressive results and their important clinical implications, it is unfortunate that the Singh et al review is unlikely to make a significant difference to clinical practice. There are many reasons why physical activity is not used as a first-line intervention for depression and other mental health problems, but one of the problems is that the field has not really addressed an issue I highlighted in a review of the field a quarter of a century ago. The evidence that PA can be an effective stand-alone or adjunctive intervention for a range of mental health problems is diluted amongst the public health/ mental wellbeing studies focusing on lifestyle/ general health/ quality of life outcomes. What we need are effectively powered randomised controlled trials of carefully designed PA interventions compared to medication and psychological therapy in primary and secondary care clinical populations. It is important to note that, similar to the Singh et al. review, the Cochrane review ‘Exercise for depression’ (Cooney et al., 2013) included a preponderance of trials with non-clinical populations (23 out of the 39 trials included in the review).
Nonetheless, it is encouraging to see that the 2022 update of the NICE Guideline for Depression in adults (NG222) now includes the following:
‘Advise people that doing any form of physical activity on a regular basis (for example, walking, jogging, swimming, dance, gardening) could help enhance their sense of wellbeing. The benefits can be greater if this activity is outdoors.’

The Singh et al. review has implications for future research (e.g. neuromolecular mechanisms by which PA appears to improve depression) and clinical practice (e.g. resistance exercise was most effective for depression, while Yoga and other mind–body exercises were most effective for anxiety).

Research should not focus on neuroscience alone, however, as the mechanism responsible for the relationship between physical activity and mental health is complex and lies in a combination of biological, psychological and social factors (Biddle & Mutrie, 2001). The field therefore would also benefit from in-depth qualitative studies. A good example is a study by Crone et al. (2005) of people referred to ‘exercise prescription’ schemes, which demonstrated the importance of contextual factors such as social network, environment, culture and social support. However, this study also concluded that PA referral schemes appeared to be better suited to the needs of physical- than mental- health patients. This points to the need to research which factors encourage people referred for different mental health problems to engage with, and benefit from, different types of physical activity. Motivational factors may be unique to an individual, but we may find that a physical activity intervention that optimises the ‘therapeutic ingredients’ will have the best outcomes; for example, a specialist PA activity which is provided within a setting which maximises both social support and interaction with nature.

REFERENCES
Burbach, F. R. (1997). The efficacy of physical activity interventions within mental health services: Anxiety and depressive disorders. Journal of Mental Health, 6(6), 543-566.
Cooney, G. M., Dwan, K., Greig, C. A., Lawlor, D. A., Rimer, J., Waugh, F. R., ... & Mead, G. E. (2013). Exercise for depression. Cochrane database of systematic reviews, (9).
Crone, D., Smith, A., & Gough, B. (2005). “I feel totally alive, totally happy and totally at one”: A psycho-social explanation of the physical activity and mental health relationship from the experiences of participants on exercise referral schemes. Health Education Research, 20(5), 600–611.
Biddle, S. J. H., & Mutrie, N. (2001). Psychology of physical activity determinants, well-being and interventions.Routledge: London.
Singh, B., Olds, T., Curtis, R., Dumuid, D., Virgara, R., Watson, A., ... & Maher, C. (2023). Effectiveness of physical activity interventions for improving depression, anxiety and distress: an overview of systematic reviews. British Journal of Sports Medicine.

We wish to commend Horan et al. (Horan et al., 2022) on their systematic review and meta-analysis which established overall, match and training IIRs in senior women’s football. It is encouraging to see continued work in this specific area of women’s football epidemiological research.

We would like to draw the authors attention to the following error contained within their work. We respectfully request that it is amended accordingly so that the readership are aware of all available work in this area.

Horan et al. (Horan et al., 2022) refer to the systematic review and meta-analysis of López Valenciano et al (López-Valenciano et al., 2021) which they report was recently ‘criticised’ in a published commentary by Mayhew et al (2021). The authors use the following citation:

30. Mayhew, L. et al. (2021) ‘Incidence of injury in adult elite women’s football: a systematic review and meta-analysis’, BMJ Open Sport & Exercise Medicine, 7(3), p. e001094. doi:10.1136/bmjsem-2021-001094

The readership should be aware that the citation Horan et al. (Horan et al., 2022) use in their work is not a published commentary but a systematic review and meta-analysis on the incidence of injury in elite women’s football. Our publication was PROSPERO registered and published ahead of Horan et al. (Horan et al., 2022) in BJSM’s sister journal (BMJ Open Sport & Exercise Medicine).

The corrected citation should be:

Mayhew, L., Johnson, M.I. and Jones, G. (2021) ‘Comment on: “Injury Profile in Women’s Football: A Systematic Review and Meta‑analysis’’, Sports Medicine, 51(12), pp. 2665–2666. doi:10.1007/s40279-021-01531-9.

Our systematic review and meta-analysis is thus cited in Horan et al (2022) but is not referred to in text as a previous systematic review and meta-analysis within this area of research. The readership should be made aware of all relevant work and we invite the authors to comment on the contents of this letter.

Yours Sincerely

Lawrence Mayhew

There is absolutely no doubt that physical activity is a beautiful phenomenon. In the above study, the study is fair to the extent that those subjects who regularly exercised had lesser hospitalisations. Here both reason and effect exist, but can a direct causal relationship be established between the two?
Can it be inferred beyond doubt that "the vaccine prevented complications of Covid-19 because exercise strengthened the immune response? The possibility of such a remarkable effect in the short term is pretty unlikely. And all the more, such findings can't be generalised to a larger population.

Authors seem to be ignoring a hidden confounder affecting the validity of the study, and this confounder is 'frailty'. Simply those doing less exercise were unable to do so because they were frail. And obviously, frailty can be present independent of comorbidities like DM, heart failure or obesity, which were evenly matched between the high and low-exercise groups.

So, the correct conclusions will likely differ if this confounder is considered. one may not forget that 'Correlation, even if present in a statistically significant portion, may not amount to causation.

The study might prompt some frail people or even morbidly obese people to engage in heavy exercise soon after the vaccination despite muscle aches and fever (common side effects of the Covid-19 vaccines). And these might have disastrous consequences. So the words of caution need to be stressed.
Nevertheless, the role of exercise in a healthy population should not be undermined.

The topic of transgender inclusion in women’s sports is politically fraught. Sport’s governing bodies are grappling with the competing priorities of inclusivity and fairness due to any perceived competitive advantage above and beyond the large and broad continuum of biological variables found within cisgender women (e.g. height, bone mass, bone length, fiber cross-sectional diameter, etc.) associated with testosterone exposure during puberty. This active area of research is rapidly evolving due to the multitude of new studies published over the previous 5 years. In fact, there have been over a dozen primary prospective and case-control research studies published on this topic since 2018 resulting in the lowering of the maximum allowable testosterone level in transgender elite athletes (i.e., from 5.0 to 2.5nmol/L) by several sports’ governing bodies.

The preponderance of evidence suggests that hematological differences in hematocrit, red cell number, and hemoglobin are largely normalized within 120 days of testosterone suppression, which is biologically plausible as this corresponds with the average lifespan of a red cell (~ 120 days). Since oxygen delivery to peripheral tissues is performance limiting in aerobic sports, any competitive advantage is likely largely diminished within a year of testosterone suppression. Studies evaluating changes in strength, muscle mass, and body composition are more equivocal and most likely occur over a longer time span (12-36 months).

Few studies have evaluated cardiopulmonary differences in transgender women relative to cisgender women or men. The recent publication by Alvares et. al. evaluated cardiopulmonary capacity and grip strength in a small cohort of non-athlete cisgender and transgender women (CW and TW) and cisgender men (CM) in San Paulo, Brazil. 15 transgender women were recruited from a clinic that specializes in the treatment transgender patients. The average age of the TW was 34.2 +/- 5.2 years with an average duration of hormonal treatment of 14.4+/-3.5 years (median age of treatment initiation was 17 years old). Although the TW subjects were on hormonal treatment for over a decade, 11 of the 15 subjects were dependent on chemical testosterone suppression (i.e., non-gonadectomized). The median testosterone level over the previous 12 months for the TW subjects was 3.5nmol/L with 4 of the subjects above 7nmol/L, which is within the range observed CM group. As noted above, several sports’ governing bodies require testosterone suppression below 2.5nmol/L throughout the entire year. Prospective testosterone data for each subject was not provided so it is unclear how many TW subjects meet these criteria, however median levels presented in supplemental figure 1 suggest that at least 8 out of 15 of the subjects do not meet this criterion. Despite the suboptimal hormonal control, hemoglobin levels of the TW were not different than CW and both groups were significantly lower than the CM group. Although the groups were matched by age and activity, they were not weight matched. The average body weights were 60.8kg, 78.1kg, and 81.3kg for the CW, TW, CM groups respectively (CW vs TW and CW vs CM were significantly different; P < 0.001).

The authors performed cardiopulmonary exercise testing on a treadmill using a ramp protocol to exhaustion. They measured oxygen consumption at rest (prior to running), at anaerobic threshold (AT), at respiratory compensation point (RCP), and peak consumption. Values were provided on an absolute basis (mL/min) at rest, AT, RCP. VO2 peak was presented on absolute and relative basis (relative to total body weight and fat free mass [FFM]; L/min/kg). The absolute oxygen consumption at rest, at RCP, and peak consumption were higher in the TW group relative to the CW group. This is not surprising since the average body weight of the TW was 22% heavier than the CW group.

Conceptually speaking, someone that is heavier (i.e. has a higher fat free mass) is more metabolically active and will consume more oxygen per time period. The authors do present peak oxygen consumption normalized to total body weight and fat free mass. When doing so, differences in the peak oxygen consumption disappear. In fact, when normalized to FFM, VO2 peak was 11% less in the TW group relative to the CW group although the differences were not statistically different. When corrected to body weight, no differences in oxygen consumption were observed between the CW and TW groups (Rest - 4.2 vs 4.0L/kg/min; AT - 21.6 vs. 21.5L/kg/min; RCP - 29.6 vs. 31.5 L/kg/min; Peak - 33.4 vs 35.7 L/kg/min). This is an important point because it suggests that there are no differences in cardiopulmonary capacity in TW compared to CW when normalized to body weight. Although these subjects reported high activity levels, the peak oxygen consumption (VO2 peak) for the CW, TW, and CM groups was roughly half the VO2 peak observed in most elite athletes (>60 L/kg/min). These results should not be extrapolated to elite athletes.

The authors also assessed grip strength to evaluate whether there were any strength differences between TW and CW and CM. There was a statistically significant increase in grip strength between TW and CW, however this finding was no longer significant after normalizing to body weight. Nevertheless, it is unclear the relevance of grip strength to predicting any performance advantage to most elite or professional sports.

Owing to the scientific rigor and careful interpretation of results from previous case-control and prospective research studies, the results from these studies have advanced our understanding of the physiological changes associated with testosterone exposure during puberty and subsequent withdrawal on human exercise performance. The amalgamation of the available data has allowed sports’ governing bodies the ability to make highly informed policy decisions on managing a balance between inclusivity and fairness in female transgender athletes. It is incumbent that all new studies in this area of research are of high scientific rigor and the associated conclusions are appropriate for the data that are presented because the results and the language used have imminent ramifications for the inclusion of transgender athletes to compete in sport. The conclusions presented by Alvares et al are incomplete and not fully supported by the data. Further and perhaps more importantly, the conclusions by the authors suggesting that TW have higher cardiopulmonary function (unadjusted for body weight) is harmful to the sporting community at large because it submits false evidence of a competitive advantage. Although the study was conducted in non-athletes, the authors suggest the results from their study may inform inclusion policies for transgender athletes. In fact, the data from Alvares et al suggest that TW do not have improved cardiopulmonary function relative to CW or TW when normalized to body weight. Thus, the study does not provide evidence of a competitive advantage in sports in this small cohort of non-athletes. As such, it does not support further restrictions of transgender athletes from sport.