Adaptation to military operational stress is a complex physiological response that calls upon the sympathetic nervous system (SNS), hypothalamic pituitary adrenal (HPA) axis and immune system, to create a delicate balance between anabolism and catabolism and meet the demands of an ever‐changing environment. As such, resilience, the ability to withstand and overcome the negative impact of stress on military performance, is likely grounded in an appropriate biological adaptation to encountered stressors. Neuroendocrine [i.e. cortisol, epinephrine (EPI), norepinephrine (NE), neuropeptide‐Y (NPY), and brain derived neurotropic factor (BDNF)], inflammatory [i.e. interleukin 6 (IL‐6), IL‐1β, IL‐4, IL‐10 and tumour necrosis factor (TNF)‐α], as well as growth and anabolic [i.e. insulin‐like growth factor‐I (IGF‐I), testosterone, and dehydroepiandrosterone (DHEA)] biomarkers independently and interactively function in stress adaptations that are associated with a soldier's physical and psychological performance. In this narrative review, we detail biomarkers across neuroendocrine, inflammatory, and growth stimulating domains to better elucidate the biological basis of a resilient soldier. The findings from the reviewed studies indicate that military readiness and resiliency may be enhanced through better homeostatic control, better regulated inflammatory responses, and balanced anabolic/catabolic processes. It is unlikely that one class of biomarkers is better for assessing physiological resilience. Therefore, a biomarker panel that can account for appropriate balance across these domains may be superior in developing monitoring frameworks. Real‐time physiological monitoring to assess biomarkers associated with resilience will be possible pending more sophisticated technologies and provide a field‐expedient application for early identification and intervention of at‐risk soldiers to improve military resiliency.

Extracellular vesicles (EVs) are established mediators of adaptation to exercise. Currently, there are no published data comparing changes in EVs between men and women after resistance exercise. We tested the hypothesis that EV profiles would demonstrate a sex-specific signature following resistance exercise. Ten men and 10 women completed an acute heavy resistance exercise test for back squats using 75% of their one-repetition maximum. Blood was drawn before and immediately after exercise. EVs were isolated from plasma using size exclusion chromatography and stained with antibodies associated with exosomes (CD63), microvesicles (VAMP3), apoptotic bodies (THSD1), and a marker for skeletal muscle EVs (SGCA). CD63+ EV concentration and proportion of total EVs increased 23% (P = 0.006) and 113% (P = 0.005) in both sexes. EV mean size declined in men (P = 0.020), but not in women, suggesting a relative increase in small EVs in men. VAMP3+ EV concentration and proportion of total EVs increased by 93% (P = 0.025) and 61% (P = 0.030) in men and women, respectively. SGCA+ EV concentration was 69% higher in women compared with men independent of time (P = 0.007). Differences were also observed for CD63, VAMP3, and SGCA median fluorescence intensity, suggesting altered surface protein density according to sex and time. There were no significant effects of time or sex on THSD1+ EVs or fluorescence intensity. EV profiles, particularly among exosome-associated and muscle-derived EVs, exhibit sex-specific differences in response to resistance exercise which should be further studied to understand their relationship to training adaptations.

Combat roles are physically demanding and expose service personnel to operational stressors such as high levels of physical activity, restricted nutrient intake, sleep loss, psychological stress, and environmental extremes. Women have recently integrated into combat roles, but our knowledge of the physical, physiological, and psycho‐cognitive responses to these operational stressors in women is limited. The aim of this narrative review was to evaluate the evidence for sex‐specific physical, physiological, and psycho‐cognitive responses to real, and simulated, military operational stress. Studies examining physical and cognitive performance, body composition, metabolism, hypothalamic‐pituitary‐gonadal axis, and psychological health outcomes were evaluated. These studies report that women expend less energy and lose less body mass and fat‐free mass, but not fat mass, than men. Despite having similar physical performance decrements as men during operational stress, women experience greater physiological strain than men completing the same physical tasks, but this may be attributed to differences in fitness. From limited data, military operational stress suppresses hypothalamic‐pituitary‐gonadal, but not hypothalamic–pituitary–adrenal, axis function in both sexes. Men and women demonstrate different psychological and cognitive responses to operational stress, including disturbances in mood, with women having a higher risk of post‐traumatic stress symptoms compared with men. Based on current evidence, separate strategies to maximize selection and combat training are not warranted until further data directly comparing men and women are available. However, targeted exercise training programmes may be advisable to offset the physical performance gap between sexes and optimize performance prior to inevitable declines caused by intense military operations.

Conkright, WR, Beckner, ME, Sinnott, AM, Eagle, SR, Martin, BJ, Lagoy, AD, Proessl, F, Lovalekar, M, Doyle, TLA, Agostinelli, P, Sekel, NM, Flanagan, SD, Germain, A, Connaboy, C, and Nindl, BC. Neuromuscular performance and hormonal responses to military operational stress in men and women. J Strength Cond Res 35(5): 1296–1305, 2021—Women have recently been integrated into ground close combat positions; however, there are limited data in women in these roles. We aimed to test the hypothesis that there would be no sex-specific neuromuscular responses, but hormonal signaling would be differentially impacted when exposed to simulated military operational stress (SMOS). Neuromuscular performance was assessed daily using a tactical mobility test (TMT) in 54 male and 15 female military members. Blood was drawn before/after TMT. Mood states were assessed each morning. Unloaded 300-m shuttle time increased 6% in both sexes and remained 7% higher after 1 day of recovery compared with baseline (p < 0.05 for both), whereas performance was maintained in other TMT events (p > 0.05). Growth hormone increased in men, but not women, before to after TMT (p < 0.001 vs. p = 0.086). Women experienced a greater decline in insulin-like growth factor-I across days compared with men ( = 0.778 vs. 0.209, respectively, p < 0.001). Brain-derived neurotrophic factor increased significantly in men only from before to after TMT on day 1 (men: +107% vs. women: +10%) but no difference on days 3 or 4. Cortisol increased 69% from before to after TMT when averaged by sex and day. Negative mood states (depression, tension, and anger) and altered hormonal concentrations were associated with poorer TMT performance. Acute SMOS differentially impacted circulating hormonal milieu in men and women, but no differences in physical performance responses. Unloaded 300-m shuttle was negatively impacted while other fitness domains were maintained. Relationships between performance and mood/endocrine signaling highlight the potential for self-report measures and biomarkers to serve as indicators of performance change.

Sex is understudied in EV research, and most studies limit EV analysis to single stress conditions such as exercise. Multistress conditions consisting of physical exertion and sleep and caloric restriction are common in real-world settings. We demonstrate that physical exertion results in sex-specific EV signatures and that EV profiles vary according to single versus multistress conditions. Our data highlight important biological and ecological characteristics that should be considered in EV research.