Progesterone and estrogen influence baseline breathing parameters and chemoreflexes in menstruating women

The hypoxic and hypercapnic ventilatory responses (HVR, HCVR, respectively) are the reflex increases in breathing in response to decreases in arterial oxygen or increases in arterial carbon dioxide partial pressures. These reflexes are highly variable both within individuals because of pathologies or environmental exposures, as well as across populations. However, the mechanisms underlying individual variation in these responses are still under investigation. Despite decades of research examining the effects of sex hormones progesterone and estrogen on ventilatory chemoreflexes, there remains no strong consensus and data are conflicting. Some studies have reported differences in the HVR in menstruating women compared to men and postmenopausal women, but few studies investigate this link further, and data within menstruating non-pregnant women are less conclusive. We directly measured plasma progesterone and estradiol levels and the HVR and HCVR using the Duffin modified rebreathing chemoreflex method, in 40 healthy, nonpregnant menstruating women. Our results indicate that higher progesterone levels were not associated with HVR, HCVR or the ventilatory recruitment threshold when measured in hyperoxic (inspired PO2 = 228 mmHg) or hypoxic (end-tidal PO2 = 50 mmHg) conditions, especially when adjusting for age as a covariate. Our results indicate a positive correlation with total ventilation and estradiol when adjusting for age as a covariate (F(1, 77) = 16.9063, p = 9.739e-5). Overall, these findings indicate that the impact of progesterone on the isocapnic HVR in menstruating women may be moderate at lower hormone levels, while estradiol seems to influence baseline ventilation.