This summer marks the 40th anniversary of the first women’s Olympic marathon. Since then, women have been closing the gap with men in the results tables of ultra-endurance events, such as the Marathon des Sables, Ultra Trail du Mont Blanc and the Barkley marathons. Women have also pioneered extreme adventurous and occupational endeavours which, until recently, were the preserve of men. These include physically demanding combat roles in the military, polar traverse expeditions and ultra-endurance rowing.

Intense and sustained exercise can lead to an energy deficit (energy expenditure higher than dietary energy intake), which activates the hypothalamic-pituitary-adrenal (HPA) axis to increase circulating glucocorticoid levels and improve substrate availability to tissues. This adaptive response is fundamental to survival. However, as a high proportion of available energy is apportioned to locomotion, prolonged downregulation of less essential processes may be pathological, e.g. suppressed reproductive function.¹ The suppression of reproductive function is an adaptive response to stress, with the aim of reducing likelihood of conception during times when a successful live birth is less probable, but the subsequent suppression of sex steroid hormones has other effects that can be harmful to health (e.g. musculoskeletal) and aspects of physical and cognitive performance.

LESSONS FROM THE ANTARCTIC

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The Ice Maiden expedition traversed 1,700km in 62 days. Crown Copyright

Polar ski touring is an example of vigorous physical activity and energy deficit with high ‘stationarity’, i.e. a day-to-day routine which remains largely unchanged over several weeks. During the first all-female Antarctic traverse expedition, six women completed the 1700km land mass traverse in 62 days (the largest team to ever do so of any gender, see images) and demonstrated preserved pituitary gonadotroph function² and bone density,³ despite a mean 9kg weight loss and marked activation of the HPA axis.

We recently studied a larger Antarctic expedition of six men and three women. In this cohort, greater loss of fat mass and fat-free mass was seen among men than among women,⁴ a separation which became apparent after around 30 days of activity. This finding was consistent with some evidence from military cohorts that women better protect fat-free mass in multi-stressor environments than do men.

Energy deficits are a major contributing factor to fat-free mass loss. Women typically have lower body size than men – which contributes significantly to the difference in energy cost in locomotive tasks. This means they may also find it easier than men to maintain an energy balance in environments when energy intake is restricted by logistical challenges (e.g. the amount of food you can carry or the time available for eating).

Salivary steroid levels in this mixed expedition suggested greater activation of the HPA axis among women than in men, and more suppression of testosterone levels among men (unpublished data). Studies comparing metabolic function during prolonged exercise have demonstrated a sexually dimorphic pattern of adaptation, with women preferentially utilising more fat than men.⁵ Storing and utilising more adipose tissue allows women to preserve lean mass during an energy deficit, mitigating maladaptive endocrine effects. This sex-specific difference appears to become more relevant as exercise is sustained.

MILITARY TRAINING

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The six soldiers of the Ice Maiden expedition at the South Pole; the first all-female team to ski across Antarctica using muscle power alone. Crown Copyright

While women may compare favourably to men in many adaptations to an energy deficit, they demonstrate higher rates of pertinent adverse outcomes in settings that expose them to multiple concurrent stressors. For example, during arduous military training, women experience higher rates of stress fracture than men.⁶ 

It is difficult to compare male and female reproductive outcomes, but rates of ovarian dysfunction are high during military training.⁷ Female reproductive dysfunction during military training is associated with maladaptive metabolic responses, possibly driven by heightened average glucocorticoid exposure.⁸ We conducted a study of HPA axis and pituitary gonadotroph responses to 29 weeks of basic military training in nine men and 34 women. The HPA axis was markedly more activated among women than in men, with evidence of greater suppression of gonadotroph function (unpublished data).

It is difficult to precisely delineate the individual stressors which contribute to stressful circumstances such as military training. In this study, men demonstrated more energy deficit than women,⁹ so it is perhaps less likely that negative energy balance was a major contributing factor. Other stressors which could plausibly explain these findings include sleep deprivation, the enforced nature of training (an ‘external locus of control’), hydration status and psychological coping strategies. Altered sleep has a potentiating effect on reactivity of the HPA axis¹⁰ and is commonly reported during military training, with greater HPA axis responsiveness seen in women under sleep deprivation.¹¹ Dehydration leads to co-activation of HPA axis and arginine vasopressin in a sex-specific manner.¹² Whilst the athlete literature highlights energy deficits as having the major contributing role in impaired reproductive function in female athletes, women undergoing arduous multi-stressor training or expeditions may experience reproductive dysfunction as a result of a number of individual factors or the combination of these factors.

FUTURE STUDIES

The next steps are to better understand individual observations in environments that involve multiple concurrent stressors (for instance during military or police employment), and to define which factors contribute to maladaptive metabolic and endocrine responses. Both basic science and clinical interventional approaches are needed, to determine how factors may affect the HPA axis in a sex-specific manner, contributing to female reproductive dysfunction and associated pathologies. This will allow the development and trialling of mitigating solutions which will optimise female integration into these environments, to capitalise on increased diversity.

ROBERT M GIFFORD
Honorary Clinical Senior Lecturer, University of Edinburgh and Royal Centre of Defence Medicine, UK

THOMAS J O’LEARY
Army Health and Performance Research, British Army

REFERENCES

1. Gifford RM & Woods DR 2020 The Endocrinologist www.endocrinology.org/endocrinologist/135-spring20/features/exploring-endocrine-physiology-during-arduous-exercise.
2. Gifford RM et al. 2019 Medicine & Science in Sports & Exercise https://doi.org/10.1249/mss.0000000000001803.
3. O’Leary TJ et al. 2019 Bone https://doi.org/10.1016/j.bone.2019.02.002.
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11. Wright KP et al. 2015 Brain, Behavior & Immunity https://doi.org/10.1016/j.bbi.2015.01.004.
12. Kacheva S et al. 2015 Clinical Endocrinology https://doi.org/10.1111/cen.12608.