Hormone replacement therapy causes a respiratory alkalosis in normal postmenopausal women

Menopause is associated with an increase in venous bicarbonate concentratio ns that is reversible with hormone replacement therapy (HRT). However, the mechanism underlying this effect is not known. To address this question, we studied the changes in acid-base indexes in the arterialized Venous blood of normal postmenopausal women commencing conjugated equine estrogen (0.625 mg/day), medroxyprogesterone acetate (MPA; 5 mg/day), their combination, o r placebo, in a double blind randomized controlled study over 3 months. Serum bicarbonate concentrations decreased significantly in the groups rece iving either MPA or estrogen plus MPA (P = 0.008). This trend was apparent as early as 2 days and reached 2.7 and 2.3 mmol/L in the respective groups by 3 months. Similar changes were seen with partial pressure of carbon diox ide (P = 0.04); a change of -0.7 kPa occurred in the estrogen plus MPA grou p at 3 months. There were no changes in bicarbonate concentrations or parti al pressure of carbon dioxide in those receiving estrogen alone or placebo. Accompanying changes in blood pH were apparent in the estrogen plus MPA gr oup, where there was an upward trend at 1 week (P = 0.056) and a significan t change from baseline (+0.013) at 3 months (P = 0.03). In the whole group, the changes in pH were inversely correlated with those in urinary excretio n of hydroxyproline (r = -0.44; P = 0.01). We conclude that HRT using conjugated estrogens and MPA produces small, but sustained, changes in acid-base status. These may contribute to the effect s of HRT and menopause on many tissues and disease processes, including the development of osteoporosis.