INTRODUCTION:
Compared to men, women exhibit distinct ventilatory regulation during exercise. However there remains a discrepancy in findings regarding the direct influence of menstrual cycle (MC) on exercise-induced chemosensitivity. This debate is partly due to methodological heterogeneity of previous studies in the objectively assessment of the MC or oral contraception (COC).
AIM: To provide insights into how fluctuations in hormonal levels during different phases of the natural MC vs COC affect ventilatory response and chemosensitivity to a cardiopulmonary exercise testing (CPET), using a phase-specific and hormonally rigorous methodology aligned with current recommendations.
METHODS:
Twenty-eight women with a natural menstrual cycle (NC; 25±4 years) and thirty women using monophasic combined oral contraception (COC; 23±3 years) were included. Groups were matched for BMI and physical activity level. All participants were nulliparous, healthy, and presented regular cycles.
Each participant performed a CPET at three randomized phases based on urinary detection confirmed by blood analyses: (Phase A) early follicular phase or day 2 of menses; (Phase B) estradiol peak by urinary detection for NC or day 12 for COC; (Phase C) progesterone peak by urinary detection for NC or day 21 for COC.
At each visit, CPET was performed in decubitus position (6 min rest, 20 W/ 2 min up to 80 W, then 20 W/min until exhaustion) with breath-by-breath measurements of ventilation (VE) and gas exchange (VO2 and VCO2). Group and phase effects were analyzed using linear mixed-effects models.
RESULTS:
At exercise, the first ventilatory threshold (VT1) level and associated VE and ventilatory equivalents (EqCO2 and EqO2) were identical between phases and groups (all p> 0.05). However, the chemosensibility, assessed by EqCO2 relative to PetCO₂ at VT1 was higher in phase C compared with phase B in both groups (NC: p<0.01; COC: p<0.05) and additionally, phase B values were higher in the COC group compared with the NC group (p<0.05). Repeated-measures correlation analysis demonstrated a significant positive association between EqCO₂/PetCO₂ at VT1and circulating progesterone concentration (r=0.43, p<0.01).
No effect was observed on VE/VCO2 slopes.
At maximal exercise, peak V̇E did not differ between phases or groups. However, EqCO₂/PetCO₂ at maximal effort was increased in phase C compared with phase B in the NC group, and remained higher in phase B of the COC group compared with NC (all p<0.05).
CONCLUSION:
Ventilatory control appears sensitive to the hormonal milieu. Progesterone-dominant phases were associated with higher ventilatory chemosensitivity, better described by EqCO₂/PetCO₂ at VT1 or maximal exercise than by the VE/V̇CO₂ slope. This index was positively associated with circulating progesterone levels, suggesting that ovarian hormones may subtly influence breathing control during exercise and gerenate additional breathing cost.