Are there sex differences in risk for exertional heat stroke? A translational approach

Giersch, Gabrielle E.W.; Garcia, Christian; Stachenfeld, Nina S.; Charkoudian, Nisha

doi:10.1113/ep090402

Cited by 15 publications

(12 citation statements)

References 75 publications

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“…The implications of these morphological differences between sexes to EHS responses remain unclear. 97 In a preclinical model of EHS, 98 female mice outperformed male mice by about 40%. 59 This finding was unexpected given that this preclinical model consists of forced wheel running in uncompensable heat (37.5°C environmental temperature and 40% relative humidity) and the greater surface area-to-mass ratio in female mice.…”

Section: Sex Differencesmentioning

confidence: 99%

Exertional heat stroke: pathophysiology and risk factors

Garcia

Rentería

Leite-Santos

et al. 2022

bmjmed

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Exertional heat stroke, the third leading cause of mortality in athletes during physical activity, is the most severe manifestation of exertional heat illnesses. Exertional heat stroke is characterised by central nervous system dysfunction in people with hyperthermia during physical activity and can be influenced by environmental factors such as heatwaves, which extend the incidence of exertional heat stroke beyond athletics only. Epidemiological data indicate mortality rates of about 27%, and survivors display long term negative health consequences ranging from neurological to cardiovascular dysfunction. The pathophysiology of exertional heat stroke involves thermoregulatory and cardiovascular overload, resulting in severe hyperthermia and subsequent multiorgan injury due to a systemic inflammatory response syndrome and coagulopathy. Research about risk factors for exertional heat stroke remains limited, but dehydration, sex differences, ageing, body composition, and previous illness are thought to increase risk. Immediate cooling remains the most effective treatment strategy. In this review, we provide an overview of the current literature emphasising the pathophysiology and risk factors of exertional heat stroke, highlighting gaps in knowledge with the objective to stimulate future research.

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Section: Sex Differencesmentioning

confidence: 99%

Exertional heat stroke: pathophysiology and risk factors

Garcia

Rentería

Leite-Santos

et al. 2022

bmjmed

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“…Although the absolute number of EHS incidences in women is less than men, women are not exempt from this lifethreatening condition (Belval et al, 2020;DeMartini et al, 2015;Giersch et al, 2022). As women's representation in sport, the military and industry continues to grow under the current societal and legislative climate (Ministry of Defence, 2014;Brushlinksy et al, 2017;International Olympic Committee, 2018) so too will the number of females exposed to exertional and environmental heat loads and therefore at risk of EHS.…”

Section: Cold Water Immersion In Hyperthermic Womenmentioning

confidence: 99%

Treating exertional heat stroke: Limited understanding of the female response to cold water immersion

2022

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According to an expansive body of research and best practice statements, whole-body cold water immersion is the gold standard treatment for exertional heat stroke. However, as this founding evidence was predominantly drawn from males, the current guidelines for treatment are being applied to women without validation. Given the recognised differences in thermal responses experienced by men and women, all-encompassing exertional heat stroke treatment advice may not effectively protect both sexes. In fact, recent evidence suggests that hyperthermic women cool faster than hyperthermic men during cold water immersion. This raises the question of whether overcooling is risked if the present guidelines are followed. The current mini-review examined the literature on women’s response to cold water immersion as a treatment for exertional heat stroke and aimed to clarify whether the current guidelines have appropriately considered research investigating women. The potential implications of applying these guidelines to women were also discussed.

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“…However, when examining the most severe heat illness outcome, i.e. heat stroke, the majority of studies, both in and outside the military, are consistent with higher incidence rates in males [ 3 , 9 ], though there is heterogeneity in results [ 10 ] and questions remain regarding whether this is behavioral or physiological in origin [ 11 ]. These differences in susceptibility to heat stroke are not limited to humans; e.g.…”

Section: Introductionmentioning

confidence: 99%

“…Our laboratory has developed a preclinical model of EHS in mice that has been useful in studying the sex differences in response to exercise in the heat [ 10 ]. Throughout this report, we use the abbreviation, EHS, for both the clinical condition in humans and the response of mice to our experimental EHS model.…”

Section: Introductionmentioning

confidence: 99%

The impact of castration on physiological responses to exertional heat stroke in mice

Garcia

Robinson²,

Gambino³

et al. 2022

PLoS ONE

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Introduction The capability of male mice to exercise in hot environments without succumbing to exertional heat stroke (EHS) is markedly blunted compared to females. Epidemiological evidence in humans and other mammals also suggests some degree of greater vulnerability to heat stroke in males compared to females. The origins of these differences are unknown, but testosterone has previously been shown to induce faster elevations in core temperature during acute, passive heat exposure. In this study, we tested the hypothesis that loss of testosterone and related sex hormones through castration would improve the performance and heat tolerance of male mice during EHS exposure. Methods Twenty-four male mice were randomly divided into 3 groups, untreated EHS mice (SHAM-EHS), castrated EHS mice (CAS+EHS) and naïve exercise controls (NAIVE). Exercise performance and physiological responses in the heat were monitored during EHS and early recovery. Two weeks later, blood and tissues were collected and analyzed for biomarkers of cardiac damage and testosterone. Results Core temperature in CAS+EHS rose faster to 39.5°C in the early stages of the EHS trial (P<0.0001). However, both EHS groups ran similar distances, exhibited similar peak core temperatures and achieved similar exercise times in the heat, prior to symptom limitation (unconsciousness). CAS+EHS mice had ~10.5% lower body mass at the time of EHS, but this provided no apparent advantage in performance. There was no evidence of myocardial damage in any group, and testosterone levels were undetectable in CAS+EHS after gonadectomy. Conclusions The results of these experiments exclude the hypothesis that reduced performance of male mice during EHS trials is due to the effects of male sex hormones or intact gonads. However, the results are consistent with a role of male sex hormones or intact gonads in suppressing the early and rapid rise in core temperature during the early stages of exercise in the heat.

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Are there sex differences in risk for exertional heat stroke? A translational approach

Cited by 15 publications

References 75 publications

Exertional heat stroke: pathophysiology and risk factors

Exertional heat stroke: pathophysiology and risk factors

Treating exertional heat stroke: Limited understanding of the female response to cold water immersion

The impact of castration on physiological responses to exertional heat stroke in mice

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