Effect of menopause on the chemical control of breathing and its relationship with acid-base status

Abstract

This study examined the role of alterations in the chemoreflex control of breathing, acid-base balance, and their interaction in postmenopausal ventilatory adaptations. A modified iso-oxic hyperoxic and hypoxic CO2-rebreathing procedure was employed to evaluate central and peripheral chemoreflex drives to breathe, respectively, in 15 healthy postmenopausal and 20 premenopausal women of similar age. Arterialized venous blood samples were collected at rest for the estimation of arterial Pco2 (PaCO2) and H+ concentration ([H+]), plasma strong ion difference ([SID]) and total weak acid ([A]tot) concentrations, and serum progesterone ([P4]) and 17β-estradiol ([E2]) concentrations. In post- compared with premenopausal women, PaCO2, [SID], and the central chemoreflex ventilatory recruitment threshold for Pco2 (VRTco2) were higher, whereas [P4] and [E2] were lower (all P < 0.05), with no significant change in central or peripheral chemoreflex sensitivity, peripheral chemoreflex VRTco2, and [A]tot. The acidifying effect of an increased PaCO2 was offset by the alkalizing effect of an increased [SID], such that [H+] was preserved in post- compared with premenopausal women. PaCO2 correlated positively with the central chemoreflex VRTco2 ( r = 0.67, P < 0.01), which in turn correlated positively with [SID] ( r = 0.53, P < 0.01) within the pooled data. In conclusion, the relative alveolar hypoventilation and attendant arterial hypercapnia in healthy post- compared with premenopausal women could be explained, in part, by the interaction of 1) reduced central, but not peripheral, chemoreflex VRTco2, 2) increased [SID], and 3) reduced circulating female sex steroid hormone concentrations.