Prevalence of excessive erythrocytosis, the main sign of chronic mountain sickness (CMS), is greater in postmenopausal Andean women than in premenopausal women. It is uncertain whether this greater prevalence is related to the decline in female hormones and ventilatory function after the occurrence of the menopause. To study this, we compared the physiological variables involved in the physiopathology of CMS [end-tidal CO2 (PetCO2, Torr) and end-tidal O2 (PetO2, Torr), arterial oxygen saturation (SaO2, %), and Hb concentration (g/dl)] and progesterone and estradiol levels between postmenopausal and premenopausal women, both in the luteal and follicular phases. Women residing in Cerro de Pasco (n = 33; 4,300 m) aged 26-62 yr were studied. Postmenopausal women compared with premenopausal women in the luteal phase had lower PetO2 (48 ± 4 vs. 53 ± 2 Torr, P = 0.005) and SaO2 levels (82 ± 12 vs. 88 ± 12%, P < 0.005) and higher PetCO2 (34 ± 2 vs. 29 ± 3 Torr, P = 0.005) and Hb concentration (19 ± 1 vs. 14 ± 2 g/dl, P < 0.005). In addition, plasma progesterone was negatively correlated with PetCO2 and positively correlated with PetO2 and SaO2. No clear relationship was found among the cycle phases between estradiol and the variables studied. In conclusion, our results reveal that, before menopause, there is better oxygenation and lower Hb levels in women long residing at altitude, and this is associated with higher levels of progesterone in the luteal phase of the cycle.