Female endocrine adaptations to arduous military training
Creators: name: Gifford, Robert Michael
Publisher: name: The University of Edinburgh
Year: 2020
Subjects: female soldiers
HPG axis function
cortisol levels
stress fractures
GnRH reduction
heat illness resilience

description: Women are able to train in arduous combat roles for the first time in the British military, yet data on sex differences in physiological responses to such physically demanding employment are lacking. Military women appear to experience high rates of fractures, menstrual disturbance and adverse psychological outcomes, conditions related to perturbations in metabolic and hormonal function. There is a paucity of studies investigating hypothalamic-pituitary-gonad (HPG) and hypothalamicpituitary-adrenal (HPA) axis function in military women. Low energy availability (EA) is an important cause of reproductive dysfunction and decreased bone mineral density (BMD) in athletes, while psychological stress and activation of the HPA axis are also associated with HPG axis suppression. Military training is physically demanding, psychologically stressful and frequently takes place in extreme climates. Therefore, the work in this thesis aimed to characterise female endocrine adaptations to arduous military in two settings: basic military training in the UK and highly arduous exercise in extreme cold. To address female responses to extreme heat, relative rates of heat illness (HI) among men and women were compared in a systematic review and meta-analysis. Female metabolic and endocrine adaptations to basic military training were explored in a cohort study of women undertaking the 11-month Commissioning Course at the Royal Military Academy, Sandhurst. Changes in body composition were measured by whole-body dual-energy-x-ray absorptiometry (DXA) at baseline and after 3, 7 and 11 months. Energy availability was assessed over 10-day periods using goldstandard techniques during months 3, 6 and 10 of training. Fasting blood sampling at baseline and after 7 and 11 months assessed leptin, insulin and glucose, as well as cortisol, cortisol binding globulin (CBG), oestradiol, anti-Müllerian hormone (AMH), inhibin B and bone turnover markers. Dynamic assessment of the HPG and HPA was undertaken using Combined Hypothalamic-pituitary-Ovarian and adrenal Cortex (CHOC) tests (LH/FSH and cortisol response to gonadotrophin releasing hormone (GnRH) and adrenocorticotrophic hormone, respectively, at five time points over 1 hour), at baseline and after 9 months. Psychological stress and mood were assessed regularly using questionnaires. Diurnal saliva cortisol was measured approximately every five weeks of training, and 1cm hair samples were assayed for cortisol to give an average monthly cortisol profile. A urinary progesterone: creatinine ratio cut-off was validated and used to determine if ovulation had taken place in women not using hormonal contraceptives, throughout the Commissioning Course. Changes in BMD were explored using DXA. Sixty one female Officer Cadets commenced the study (mean age 24.0 ±0.3 years) of whom 52 completed the study and the Course (8 withdrew due to musculoskeletal injuries; one changed career). Fat mass decreased 0.8kg from baseline to month 3 of training, increased 1.8kg to month 7 and reverted to baseline by month 11; fatfree mass did not change. Leptin and insulin resistance increased in association with fat mass. The assessment of EA was hampered by underreporting of energy intake by around 30%, however this measure of EA was weakly associated with physical performance, and paradoxically inversely associated with change in fat mass, suggesting compensatory over-eating after periods of arduous training and low energy intake. Questionnaires showed lower mood, increased stress and greater sleep deprivation during the course. Diurnal cortisol variability peaked in the first month of training, followed by habituation over the ensuing 10 months. Fasting plasma cortisol decreased, while CBG remained stable during the Course. Hair cortisol increased throughout, possibly reflecting physical exercise. Cortisol response to ACTH was modestly lower at 9 months than baseline. These data suggest a healthy overall response of the HPA axis to demonstrably arduous training. Of 22 participants (36%) not using hormonal contraceptives, 7 (32%) reported increased menstrual frequency and 7 (32%) reported amenorrhoea or oligomenorrhoea. Of cycles with corresponding urine concentrations, 80% were anovulatory. LH and FSH responses to GnRH were suppressed after 9 months and this effect was apparent in both users and non-users of hormonal contraceptives (regardless of type). Oestradiol, FSH and inhibin B increased during the course, but there was no change in AMH, suggesting hypothalamic suppression of the HPG axis and follicular dysgenesis. Bone turnover was modestly increased, reflected in higher markers of both bone formation and resorption after 8 and 11 months. Total BMD reduced slightly, with modest regional losses from arms, legs and ribs, while trunk, spine and pelvis BMD were preserved. The female response to arduous exercise in extreme cold was explored in six participants (median (range) 32.7 (28.6–36.1) years) undertaking the first unassisted all-female team crossing of Antarctica. The measures used above were adapted for use 1 month pre-expedition and 5 and 14 days post-expedition; no throughexpedition measurements were possible, and the CHOC test was performed after low-dose dexamethasone suppression. Mean (SD) weight loss was 10.1 (2.3) kg, constituting fat and not fat-free mass. Fasting oestradiol, cortisol and insulin resistance were unaffected, except leptin, which fell during the expedition and recovered partially after 14 days. Hair cortisol was elevated during the expedition. Cortisol, LH and FSH responsiveness were suppressed prior to the expedition, but were unchanged change immediately afterwards. LH responsiveness was higher than pre-expedition at expedition +14 days. Bone turnover was uncoupled immediately after the expedition, with higher resorption markers and lower formation markers, resolving after 14 days. Total BMD was unaffected. The systematic review and meta-analysis included data containing comparable male and female rates of HI. Incident rate ratios were calculated and adjusted, where possible, for severity, occupation and age. Contrary to expectations based on published laboratory studies of sex-related physiology, the systematic review of found consistently higher rates of HI reported among men than women. The metaanalysis found HI rates were over twice as high in men than women (mean (95% CI) incident risk ratio 2.28 (1.66-3.16)). This pattern was consistent across the age span and all severities of HI, and was greater in occupational HI than non-occupational HI (5.66 (2.53-13.64) vs 2.96 (2.14-4.10). In conclusion, this thesis demonstrated that women in basic military training do experience suppression of the HPG axis, despite long-term energy sufficiency with evidence of compensatory overeating and resilient HPA axis function. Resilient endocrine function in women who crossed Antarctica provides a proof of concept that with appropriate selection, nutrition and preparation, women can benefit from extremely arduous training. Women are also resilient to extreme heat, as evidenced by lower rates of HI than in men. The mechanism underlying reproductive dysfunction and associated pathology in women requires further elucidation but need not preclude women from entering such roles.