Progesterone and its analogues are known to influence ventilation. Therefore, the purpose of this study was to investigate the role of endogenous and pharmaceutical female sex hormones in ventilatory control during the activation of the metaboreflex, mechanoreflex, and CO2 chemoreflex. Women aged 18–30 taking (n = 14) or not taking (n = 12) oral contraceptives (OC and NOC, respectively) were tested in the low hormone (LH) and high hormone (HH) conditions corresponding to the early follicular and mid‐luteal phases (NOC) or placebo and high‐dose pills (OC). Women underwent three randomized trials: (a) 3 min of passive leg movement (PLM), (b) 2 min of 40% maximal voluntary handgrip exercise followed by 2 min of post‐exercise circulatory occlusion (PECO), and (c) 5 min of breathing 5% CO2. We primarily measured hemodynamics and ventilation. During PLM, the OC group had a smaller pressor response (p = .012). During PECO, the OC group similarly exhibited a smaller pressor response (p = .043) and also exhibited a greater ventilatory response (p = .024). Lastly, in response to breathing 5% CO2, women in the HH phase had a greater ventilatory response (p = .022). We found that OC use attenuates the pressor response to both the metaboreflex and mechanoreflex while increasing the ventilatory response to metaboreflex activation. We also found evidence of an enhanced CO2 chemoreflex in the HH phase. We hypothesize that OC effects are from the chronic upregulation of pulmonary and vascular β‐adrenergic receptors. We further suggest that the increased cyclic progesterone in the HH phase enhances the chemoreflex.

Women experience fluctuating orthostatic intolerance during the menstrual cycle, suggesting sex hormones may influence cerebral blood flow. Young (aged 18–30) healthy women, either taking oral contraceptives (OC; n = 14) or not taking OC (NOC; n = 12), were administered hypercapnic gas (5%) for 5 min in the low hormone (LH; placebo pill) and high hormone (HH; active pill) menstrual phases. Hemodynamic and cerebrovascular variables were continuously measured. Cerebral blood velocity changes were monitored using transcranial doppler ultrasound of the middle cerebral artery to determine cerebrovascular reactivity. Cerebral autoregulation was assessed using steady‐state analysis (static cerebral autoregulation) and transfer function analysis (dynamic cerebral autoregulation; dCA). In response to hypercapnia, menstrual phase did not influence static cardiovascular or cerebrovascular responses (all p > 0.07); however, OC users had a greater increase of mean middle cerebral artery blood velocity compared to NOC (NOC‐LH 12 ± 6 cm/s vs. NOC‐HH 16 ± 9 cm/s; OC‐LH 18 ± 5 cm/s vs. OC‐HH 17 ± 11 cm/s; p = 0.048). In all women, hypercapnia improved high frequency (HF) and very low frequency (VLF) cerebral autoregulation (decreased nGain; p = 0.002 and <0.001, respectively), whereas low frequency (LF) Phase decreased in NOC‐HH (p = 0.001) and OC‐LH (p = 0.004). Therefore, endogenous sex hormones reduce LF dCA during hypercapnia in the HH menstrual phase. In contrast, pharmaceutical sex hormones (OC use) have no acute influence (HH menstrual phase) yet elicit a chronic attenuation of LF dCA (LH menstrual phase) during hypercapnia.