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

Preston ME, Jensen D, Janssen I, Fisher JT. Effect of menopause on the chemical control of breathing and its relationship with acid-base status. Am J Physiol Regul Integr Comp Physiol 296: R722-R727, 2009. First published December 17, 2008; doi:10.1152/ajpregu.90865.2008. 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 P-CO2 (Pa-CO2) and H+ concentration ([H+]), plasma strong ion difference ([SID]) and total weak acid ([A] tot) concentrations, and serum progesterone ([P-4]) and 17 beta-estradiol ([E-2]) concentrations. In post-compared with premenopausal women, Pa-CO2, [SID], and the central chemoreflex ventilatory recruitment threshold for P-CO2 (VRTCO2) were higher, whereas [P-4] and [E-2] 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 Pa-CO2 was offset by the alkalizing effect of an increased [SID], such that [H+] was preserved in post-compared with premenopausal women. Pa-CO2 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.