Regulation of body temperature and blood pressure in women: Mechanisms and implications for heat illness risk.

Increasing global temperatures due to ongoing climate change phenomena have resulted in increased risk of exertional heat illness in otherwise healthy, young individuals who work or play in the heat. With increasing participation of women in athletic, military and industrial activities that involve exertion in the heat, there is a growing need to study female physiology in this context. Mechanisms controlling blood pressure and body temperature have substantial overlap in humans, largely due to autonomic mechanisms which contribute to both. Similarly, illnesses that result from excessive heat exposure can often be traced back to imbalances in one or more of these autonomic mechanisms. In recent years, there has been increased recognition of the importance of sex as a biological variable for basic and applied research in these areas. The goal of this paper is to present an update on the integrative physiology and pathophysiology of responses to heat stress in women (thermoregulation and blood pressure regulation). In this context, it is often the case that differences between sexes are presented as 'advantages' and 'disadvantages' of one sex over the other. In our opinion, this is an over-simplification of the physiology which ignores the nuances and complexities of the integrative physiology of responses to heat exposure and exercise, and their relevance for practical outcomes.

Relation of body surface area-to-mass ratio to risk of exertional heat stroke in healthy men and women.

Risk of exertional heat stroke (EHS) is an ongoing challenge for United States military personnel, for athletes and for individuals with occupational stressors that involve prolonged activity in hot environments. Higher body mass index (BMI) is significantly associated with increased risk for EHS in activity duty U.S. Soldiers. During exercise, heat is generated primarily by contracting skeletal muscle (and other metabolically active body mass) and dissipated based on body surface area (BSA). Thus, in compensable environments, a higher BSA·mass-1 may be a benefit to heat dissipation and decrease the risk of EHS. The purpose of the present analysis was to test the hypothesis that BSA·mass-1 ratio is an important biophysical characteristic contributing to the risk of EHS. We employed a matched case-control approach, where each individual with a diagnosis of EHS was matched to five controls who were never diagnosed with EHS but were in the same unit and had the same job title. We used a multivariate conditional logistic regression model including variables of BSA·mass-1, sex, age, military rank, and race. BSA·mass-1 significantly predicted EHS risk (P = 0.006), such that people with higher BSA·mass-1 were at lower risk of developing EHS when controlling for other potential factors such as age and race. This relationship persisted after adjustment for other anthropometric measures of body size including weight, BMI, and BSA. These data suggest that biophysical factors play an important role in EHS risk, particularly in a healthy military-aged cohort of men and women.NEW & NOTEWORTHY With the impacts of climate change yielding higher average ambient temperatures over time, the incidence of EHS for individuals participating in outdoor activities may consequently increase. With the larger sample size in this study compared with prior research in this field, we were able to use various methods that had not been applied before. For example, we were able to mutually adjust for different measurements of body size to understand which metric had the highest association with EHS risk. Understanding factors that may be modifiable may be important for developing interventions to counteract the increased risk of EHS associated with climate change.

Sex differences in thermal sensitivity and perception: Implications for behavioral and autonomic thermoregulation.

Temperature sensitive receptors in the skin and deep body enable the detection of the external and internal environment, including the perception of thermal stimuli. Changes in heat balance require autonomic (e.g., sweating) and behavioral (e.g., seeking shade) thermoeffector initiation to maintain thermal homeostasis. Sex differences in body morphology can largely, but not entirely, account for divergent responses in thermoeffector and perceptual responses to environmental stress between men and women. Thus, it has been suggested that innate differences in thermosensation may exist between men and women. Our goal in this review is to summarize the existing literature that investigates localized and whole-body cold and heat exposure pertaining to sex differences in thermal sensitivity and perception, and the interplay between autonomic and behavioral thermoeffector responses. Overall, it appears that local differences in thermal sensitivity and perception are minimized, yet still apparent, when morphological characteristics are well-controlled. Sex differences in the early vasomotor response to environmental stress and subsequent changes in blood flow likely contribute to the heightened thermal awareness observed in women. However, the contribution of thermoreceptors to observed sex differences in thermal perception and thermoeffector function is unclear, as human studies investigating these questions have not been performed.

Prospective Validation of 2B-Cool : Integrating Wearables and Individualized Predictive Analytics to Reduce Heat Injuries.

INTRODUCTION: An uncontrollably rising core body temperature (T C ) is an indicator of an impending exertional heat illness. However, measuring T C invasively in field settings is challenging. By contrast, wearable sensors combined with machine-learning algorithms can continuously monitor T C nonintrusively. Here, we prospectively validated 2B-Cool , a hardware/software system that automatically learns how individuals respond to heat stress and provides individualized estimates of T C , 20-min ahead predictions, and early warning of a rising T C . METHODS: We performed a crossover heat stress study in an environmental chamber, involving 11 men and 11 women (mean ± SD age = 20 ± 2 yr) who performed three bouts of varying physical activities on a treadmill over a 7.5-h trial, each under four different clothing and environmental conditions. Subjects wore the 2B-Cool system, consisting of a smartwatch, which collected vital signs, and a paired smartphone, which housed machine-learning algorithms and used the vital sign data to make individualized real-time forecasts. Subjects also wore a chest strap heart rate sensor and a rectal probe for comparison purposes. RESULTS: We observed very good agreement between the 2B-Cool forecasts and the measured T C , with a mean bias of 0.16°C for T C estimates and nearly 75% of measurements falling within the 95% prediction intervals of ±0.62°C for the 20-min predictions. The early-warning system results for a 38.50°C threshold yielded a 98% sensitivity, an 81% specificity, a prediction horizon of 35 min, and a false alarm rate of 0.12 events per hour. We observed no sex differences in the measured or predicted peak T C . CONCLUSION: 2B-Cool provides early warning of a rising T C with a sufficient lead time to enable clinical interventions and to help reduce the risk of exertional heat illness.

Body mass index, but not sex, influences exertional heat stroke risk in young healthy men and women.

Exertional heat stroke (EHS) remains a persistent threat for individuals working or playing in the heat, including athletes and military and emergency service personnel. However, influence of biological sex and/or body mass index (BMI) on the risk of EHS remain poorly understood. The purpose of this study was to retrospectively assess the influence of sex and BMI on risk of EHS in the active-duty US Army. We analyzed data from 2016 to 2021, using a matched case-control approach, where each individual with a diagnosis of EHS was matched to five controls based on calendar time, unit ID, and job category, to capture control individuals who were matched to EHS events by location, time, and activity. We used a multivariate logistic regression model mutually adjusted for sex, BMI, and age to compare 745 (n = 61 F) individuals (26 ± 7 yr) with a diagnosed EHS to 4,290 (n = 384 F) case controls (25 ± 5 yr). Group average BMI were similar: 26.6 ± 3.1 (EHS) and 26.5 ± 3.6 kg/m2 (CON). BMI was significantly (P < 0.0001) associated with higher risk of EHS with a 3% increase in risk of EHS for every unit increase in BMI. Notably, sex was not associated with any difference in risk for EHS (P = 0.54). These data suggest that young healthy people with higher BMI have significantly higher risk of EHS, but, contrary to what some have proposed, this risk was not higher in young women.

Countermovement jump, handgrip, and balance performance change during euhydration, mild-dehydration, rehydration, and ad libitum drinking.

Objective: To examine the effects of euhydration, mild-dehydration, rehydration, and ad libitum drinking on countermovement jump (CMJ), handgrip strength, and performance of balance error scoring system test (BESS). Methods: Eighteen healthy male subjects (mean[M]±standard deviation[SD]; age, 23±3y; body mass, 80.1 ± 9.7 kg; height, 175.8 ± 5.7 cm) participated in this study. Participants reported to the laboratory to perform CMJ, handgrip strength, and BESS with different hydration statuses (euhydrated, EUH; when they initially sensed thirst, THIRST; dehydrated, DEH; following 30 minutes of rehydration, REH; and following 24-h ad libitum drinking, AD). Results: CMJ at EUH (M±SD; 54.6 ± 3.0 cm) was significantly higher than DEH (52.8 ± 3.0 cm, p = 0.027) and REH (52.6 ± 2.8 cm, p < 0.001). However, there was no difference between DEH and REH (p = 0.643). CMJ at THIRST (54.9 ± 3.0 cm, p = 0.004) was higher than REH. Also, AD (53.8 ± 2.8 cm, p = 0.027) was higher than REH. In left handgrip strength, THIRST (48.6 ± 9.5 kg) was higher than EUH (46.7 ± 10.1 kg, p = 0.018), DEH (45.8 ± 10.0 kg, p = 0.013), REH (46.1 ± 9.5 kg, p = 0.004), and AD (47.1 ± 9.7 kg, p = 0.05). Additionally, in the single-leg stance on a foam pad, more BESS errors were found at THIRST (6 ± 2) compared to EUH (5 ± 2, p = 0.007) and AD (5 ± 2, p = 0.002). Conclusion: The findings of this study were: ∼2% of mild dehydration induced by 24-h fluid restriction decreased lower body power measured by CMJ, acute rehydration did not restore the loss of lower body power induced by dehydration, and ∼0.5-0.9% of dehydration did not decrease lower body power.

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

NEW FINDINGS: What is the topic of this review? Whether there are sex differences in exertional heat stroke. What advances does it highlight? This review utilizes a translational model between animal and human research to explore possible physical and physiological differences with respect to risk and treatment of exertional heat stroke. ABSTRACT: Exertional heat stroke (EHS) is a potentially fatal condition brought about by a combination of physical activity and heat stress and resulting in central nervous system dysfunction and organ damage. EHS impacts several hundred individuals each year ranging from military personnel, athletes, to occupational workers. Understanding the pathophysiology and risk factors can aid in reducing EHS across the globe. While we know there are differences between sexes in mechanisms of thermoregulation, there is currently not a clear understanding of if or how those differences impact EHS risk. The purpose of this review is to assess the current status of the literature surrounding EHS from risk factors to treatment using both animal and human models. We use a translational approach, considering both animal and human research to elucidate the possible influence of female sex hormones on temperature regulation and performance in the heat and highlight the specific areas with limited research. While more work is necessary to comprehensively understand these differences, the current research presented provides a good framework for future investigations.

Corrigendum: Estrogen to Progesterone Ratio and Fluid Regulatory Responses to Varying Degrees and Methods of Dehydration.

[This corrects the article DOI: 10.3389/fspor.2021.722305.].

The Rise of the Female Warfighter: Physiology, Performance, and Future Directions.

ABSTRACT: Since 1948, the United States military has been open to both men and women as permanent party service members. However, in the majority of the time since, there have been a subset of military occupational specialties (MOS), or job descriptions, open only to men. In particular, jobs requiring more intense physical and/or environmental strain were considered to be beyond the physiological capabilities of women. In the present analysis, we review the literature regarding neuromuscular, physical performance, and environmental physiology in women, to highlight that women have no inherent limitation in their capacity to participate in relevant roles and jobs within the military, within accepted guidelines to promote risk mitigation across sexes. First, we discuss performance and injury risk: both neuromuscular function and physical capabilities. Second, physiological responses to environmental stress. Third, we discuss risk as it relates to reproductive health and nutritional considerations. We conclude with a summary of current physiological, performance, and injury risk data in men and women that support our overarching purpose, as well as suggestions for future directions.

When it's time for the sex talk, words matter.

In recent years, the traditional, unspoken assumption in published biomedical research studies that the young, healthy (usually white) male is the "default human" has received increasing scrutiny and criticism. The historical underrepresentation of female participants in biomedical research has been increasingly recognized and addressed, including with the current call for papers at the American Journal of Physiology-Heart and Circulatory Physiology. Our goal in the present Perspectives is to discuss the topic of terminology (man/woman vs. male/female) for human research participants when considering sex as a biological variable. This important consideration is consistent with the importance of gender identity and related topics to psychological, emotional, and physical health. Just as pronouns are important, so is appropriate terminology when referring to human research volunteers. Despite some disagreement regarding terminology between our two groups of authors, we provide consensus recommendations. Importantly, we all agree that the most vital aspect of the present discussion is the broader focus on sex as a biological variable and appropriate inclusion of biological sex in in vitro, preclinical, and human research studies.

Estrogen to Progesterone Ratio and Fluid Regulatory Responses to Varying Degrees and Methods of Dehydration.

The purpose of this study was to investigate the relationship between volume regulatory biomarkers and the estrogen to progesterone ratio (E:P) prior to and following varying methods and degrees of dehydration. Ten women (20 ± 1 year, 56.98 ± 7.25 kg, 164 ± 6 cm, 39.59 ± 2.96 mL•kg•min-1) completed four intermittent exercise trials (1.5 h, 33.8 ± 1.3°C, 49.5 ± 4.3% relative humidity). Testing took place in two hydration conditions, dehydrated via 24-h fluid restriction (Dehy, USG > 1.020) and euhydrated (Euhy, USG ≤ 1.020), and in two phases of the menstrual cycle, the late follicular phase (days 10-13) and midluteal phase (days 18-22). Change in body mass (%BMΔ), serum copeptin concentration, and plasma osmolality (Posm) were assessed before and after both dehydration stimuli (24-h fluid restriction and exercise heat stress). Serum estrogen and progesterone were analyzed pre-exercise only. Estrogen concentration did not differ between phases or hydration conditions. Progesterone was significantly elevated in luteal compared to follicular in both hydration conditions (Dehy-follicular: 1.156 ± 0.31, luteal: 5.190 ± 1.56 ng•mL-1, P < 0.05; Euhy-follicular: 0.915 ± 0.18, luteal: 4.498 ± 1.38 ng·mL-1, P < 0.05). As expected, E:P was significantly greater in the follicular phase compared to luteal in both hydration conditions (Dehy-F:138.94 ± 89.59, L: 64.22 ± 84.55, P < 0.01; Euhy-F:158.13 ± 70.15, L: 50.98 ± 39.69, P < 0.01, [all •103]). Copeptin concentration was increased following 24-h fluid restriction and exercise heat stress (mean change: 18 ± 9.4, P < 0.01). We observed a possible relationship of lower E:P and higher copeptin concentration following 24-h fluid restriction (r = -0.35, P = 0.054). While these results did not reach the level of statistical significance, these data suggest that the differing E:P ratio may alter fluid volume regulation during low levels of dehydration but have no apparent impact after dehydrating exercise in the heat.

Sex difference in initial thermoregulatory response to dehydrated exercise in the heat.

Although it is well established that dehydration has a negative impact on thermoregulation during exercise in the heat, it is unclear whether this effect of dehydration is different between men and women, or across the phases of the menstrual cycle (MC). Twelve men and seven women (men: 20 ± 2 years, 70.13 ± 10.5 kg, 173.4 ± 6.0 cm, 54.2 ± 8.6 ml kg-1  min-1 ; women: 20 ± 2 years, 57.21 ± 7.58 kg, 161 ± 5 cm, 40.39 ± 3.26 ml kg-1  min-1 ) completed trials either euhydrated (urine specific gravity, USG ≤ 1.020, Euhy) or dehydrated (USG > 1.020, Dehy). Trial order was randomized and counterbalanced; men completed two trials (MEuhy and MDehy) and women completed four over two MC phases (late follicular: days 10-13, FDehy, FEuhy; midluteal: days 18-22, LDehy, LEuhy). Each trial consisted of 1.5 h, split into two 30 min blocks of exercise (B1 and B2, 15 min at 11 W/kg & 15 min at 7 W/kg) separated by 15 min rest in between and after. Rectal temperature (Tre ) was measured continuously and estimated sweat loss was calculated from the body mass measured before and after each block of exercise. When dehydrated, the rate of rise in Tre was greater in women in the first block of exercise compared to men, independently of the MC phase (MDehy: 0.03 ± 0.03°C/min, FDehy: 0.06 ± 0.02, LDehy: 0.06 ± 0.02, p = 0.03). Estimated sweat loss was lower in all groups in B1 compared to B2 when dehydrated (p < 0.05), with no difference between sexes for either hydration condition. These data suggest that women may be more sensitive to the negative thermoregulatory effects of dehydration during the early stages of exercise in the heat.

Availability of a Flavored Beverage and Impact on Children's Hydration Status, Sleep, and Mood.

Euhydration remains a challenge in children due to lack of access and unpalatability of water and to other reasons. The purpose of this study was to determine if the availability/access to a beverage (Creative Roots®) influences hydration in children and, therefore, sleep quality and mood. Using a crossover investigation, 46 participants were randomly assigned to a control group (CON) or an intervention group and received Creative Roots® (INT) for two-week periods. We recorded daily first morning and afternoon urine color (Ucol), thirst perception, and bodyweight of the two groups. Participants reported to the lab once per week and provided first morning urine samples to assess Ucol, urine specific gravity (USG), and urine osmolality (Uosmo). Participants also completed the questionnaires Profile of Mood States-Adolescents (POMS-a) and Pittsburgh Sleep Quality Index (PSQI). Dependent t-tests were used to assess the effects of the intervention on hydration, mood, and sleep quality. Uosmo was greater and Ucol was darker in the control group (mean ± SD) [Uosmo: INT = 828 ± 177 mOsm·kg-1, CON = 879 ± 184 mOsm·kg-1, (p = 0.037], [Ucol:INT = 5 ± 1, CON = 5 ± 1, p = 0.024]. USG, POMS-a, and PSQI were not significant between the groups. At-home daily afternoon Ucol was darker in the control group [INT = 3 ± 1, CON = 3 ± 1, p = 0.022]. Access to Creative Roots® provides a small, potentially meaningful hydration benefit in children. However, children still demonstrated consistent mild dehydration based on Uosmo, despite consuming the beverage.

Post-exercise Body Cooling: Skin Blood Flow, Venous Pooling, and Orthostatic Intolerance.

Athletes and certain occupations (e.g., military, firefighters) must navigate unique heat challenges as they perform physical tasks during prolonged heat stress, at times while wearing protective clothing that hinders heat dissipation. Such environments and activities elicit physiological adjustments that prioritize thermoregulatory skin perfusion at the expense of arterial blood pressure and may result in decreases in cerebral blood flow. High levels of skin blood flow combined with an upright body position augment venous pooling and transcapillary fluid shifts in the lower extremities. Combined with sweat-driven reductions in plasma volume, these cardiovascular alterations result in levels of cardiac output that do not meet requirements for brain blood flow, which can lead to orthostatic intolerance and occasionally syncope. Skin surface cooling countermeasures appear to be a promising means of improving orthostatic tolerance via autonomic mechanisms. Increases in transduction of sympathetic activity into vascular resistance, and an increased baroreflex set-point have been shown to be induced by surface cooling implemented after passive heating and other arterial pressure challenges. Considering the further contribution of exercise thermogenesis to orthostatic intolerance risk, our goal in this review is to provide an overview of post-exercise cooling strategies as they are capable of improving autonomic control of the circulation to optimize orthostatic tolerance. We aim to synthesize both basic and applied physiology knowledge available regarding real-world application of cooling strategies to reduce the likelihood of experiencing symptomatic orthostatic intolerance after exercise in the heat.

A 3-D virtual human thermoregulatory model to predict whole-body and organ-specific heat-stress responses.

OBJECTIVE: This study aimed at assessing the risks associated with human exposure to heat-stress conditions by predicting organ- and tissue-level heat-stress responses under different exertional activities, environmental conditions, and clothing. METHODS: In this study, we developed an anatomically detailed three-dimensional thermoregulatory finite element model of a 50th percentile U.S. male, to predict the spatiotemporal temperature distribution throughout the body. The model accounts for the major heat transfer and thermoregulatory mechanisms, and circadian-rhythm effects. We validated our model by comparing its temperature predictions of various organs (brain, liver, stomach, bladder, and esophagus), and muscles (vastus medialis and triceps brachii) under normal resting conditions (errors between 0.0 and 0.5 °C), and of rectum under different heat-stress conditions (errors between 0.1 and 0.3 °C), with experimental measurements from multiple studies. RESULTS: Our simulations showed that the rise in the rectal temperature was primarily driven by the activity level (~ 94%) and, to a much lesser extent, environmental conditions or clothing considered in our study. The peak temperature in the heart, liver, and kidney were consistently higher than in the rectum (by ~ 0.6 °C), and the entire heart and liver recorded higher temperatures than in the rectum, indicating that these organs may be more susceptible to heat injury. CONCLUSION: Our model can help assess the impact of exertional and environmental heat stressors at the organ level and, in the future, evaluate the efficacy of different whole-body or localized cooling strategies in preserving organ integrity.

Assessing the Validity of Aural Thermometry for Measuring Internal Temperature in Patients With Exertional Heat Stroke.

CONTEXT: The use of aural thermometry as a method for accurately measuring internal temperature has been questioned. No researchers have examined whether aural thermometry can accurately measure internal body temperature in patients with exertional heat stroke (EHS). OBJECTIVE: To examine the effectiveness of aural thermometry as an alternative to the criterion standard of rectal thermometry in patients with and those without EHS. DESIGN: Cross-sectional study. SETTING: An 11.3-km road race. PATIENTS OR OTHER PARTICIPANTS: A total of 49 patients with EHS (15 men [age = 38 ± 17 years], 11 women [age = 28 ± 10 years]) and 23 individuals without EHS (10 men [age = 62 ± 17 years], 13 women [age = 45 ± 14 years]) who were triaged to the finish-line medical tent for suspected EHS. MAIN OUTCOME MEASURE(S): Rectal and aural temperatures were obtained on arrival at the medical tent for patients with and those without EHS and at 8.3 ± 5.2 minutes into EHS treatment (cold-water immersion) for patients with EHS. RESULTS: The mean difference between temperatures measured using rectal and aural thermometers in patients with EHS at medical tent admission was 2.4°C ± 0.96°C (4.3°F ± 1.7°F; mean rectal temperature = 41.1°C ± 0.8°C [106.1°F ± 1.4°F]; mean aural temperature = 38.8°C ± 1.1°C [101.8°F ± 2.0°F]). Rectal and aural temperatures during cold-water immersion in patients with EHS were 40.4°C ± 1.0°C (104.6°F ± 1.8°F) and 38.0°C ± 1.2°C (100.3°F ± 2.2°F), respectively. Rectal and aural temperatures for patients without EHS at medical tent admission were 38.8°C ± 0.87°C (101.9°F ± 1.6°F) and 37.2°C ± 1.0°C (99.1°F ± 1.8°F), respectively. CONCLUSIONS: Aural thermometry is not an accurate method of diagnosing EHS and should not be used as an alternative to rectal thermometry. Using aural thermometry to diagnosis EHS can result in catastrophic outcomes, such as long-term sequelae or fatality.

Progression of human subjective perceptions during euhydration, mild dehydration, and drinking.

Thirst motivates consumption of water necessary for optimal health and cognitive-physiological functions. Other than thirst, little is known about coexisting perceptions and moods that provide information to the brain and participate in body water homeostasis. The purpose of this investigation was to observe perceptions, somatic sensations, and moods during controlled changes of hydration status. During routine daily activities interspersed with laboratory visits, 18 healthy young men (age, 23±3 y; body mass, 80.13±10.61 kg) self-reported hourly ratings (visual analog scales, VAS) of 17 subjective perceptions, across two 24-h periods (ad libitum food and water intake while euhydrated; water restriction with dry food intake [WR]) and during a 30-min rehydration session (R30, 1.46±0.47 L water intake). At the end of WR, body mass loss reached 1.67 kg (2.12%). Distinct perceptions were identified during euhydration, WR and immediately after R30. Starting approximately 4 h after WR began (body mass loss of ∼0.5%), perceptual changes included progressively intensifying ratings of thirst, mouth dryness, desire for water, and pleasantness of drinking. In comparison, immediately after R30, participants reported a reversal of the perceptions observed during WR (above) plus cooler thermal sensation, increased satisfaction, and stomach fullness. These VAS ratings suggested that aversive moods contributed to drinking behavior and supported previously published animal studies. In conclusion, this investigation delineates previously unreported perceptions and their evolution (e.g., appearance, extinction, time course) that motivated drinking during WR and discouraged overdrinking after R30.