Hormones, hypoxia and exercise hyperpnoea : considerations of the menstrual cycle and hormone replacement therapy

Background: Due to the underrepresentation of females in research there is a paucity of knowledge on the effects of oestrogen (E₂) and progesterone (P₄) on exercise ventilation. Across the menstrual cycle (MC), fluctuations in E₂ and P₄ define the early follicular (EF) and midluteal (ML) phases. Post-menopause, E₂ and P₄ are downregulated. Evidence suggests females ventilate more during the high hormone ML phase. Whether higher hormone concentrations increase ventilation during intense exercise, or in postmenopausal females using hormone replacement therapy (HRT), remains unknown. Purpose: I sought to determine the effect of E₂ and P₄ on the ventilatory response during intense exercise in young females (YF) across the MC and in older females (OF) who do or do not use HRT. Methods: Trained YFs and OFs (HRT or non-HRT) participated. During experimental days (YF: 2 days, EF & ML, OF: one day) participants were fitted with an oesophageal balloon catheter before completing five minutes of cycling at 70% of peak power in normoxia and hypoxia (FIO2=15%; two bouts each). This measured the work of breathing (W ̇B) and characterized respiratory mechanics. Serum P₄ and E₂ were measured prior to exercise. Results: For YFs, we confidently measured higher serum P₄ and E₂ in the ML compared to EF phase, although there was large between-participant variability in hormone concentration. EF and ML exercise ventilation and W ̇B were similar, while ML oxygen saturation was higher. More change in P₄ between phases resulted in the largest change in the ventilatory response regardless of condition. HRT use had no significant effect on exercise ventilation, while cardiopulmonary fitness strongly modulated the ventilatory response. Conclusion: The effect of E₂ and P₄ on exercise ventilation is present but minor in magnitude. The results provide evidence for a modulatory effect of ovarian hormones on the control of breathing. Thus, females should be included in exercise research regardless of the MC or HRT use, since the high variability in hormone concentration and the demands of intense exercise create similar ventilation across phases and between HRT groups. We found that HRT use is highly variable and does not appear to impact exercise ventilation.