Effects of estrogen on circulating "free" and total 1,25-dihydroxyvitamin D and on the parathyroid-vitamin D axis in postmenopausal women

Abstract

We evaluated the effect of estrogens on "free" and total calcitriol levels and on the calcitriol response to a hypocalcemic challenge in 12 postmenopausal women, age 55-74 yr. Endogenous calcitriol production was induced by intravenous Na-EDTA before and after conjugated estrogens, 1.25 mg/d for 30 d. Free calcitriol was determined by centrifugal ultrafiltration and by the molar ratio of calcitriol to vitamin D-binding protein (DBP). Estrogen increased fasting total calcitriol from 38.5 +/- 3.8 to 62.3 +/- 7.0 pg/ml (P less than 0.05). This was accompanied by a rise in free calcitriol from 104.5 +/- 11.4 to 158.7 +/- 16.4 fg/ml (P less than 0.05). Vitamin D-binding protein increased from 348 +/- 16 to 428 +/- 12 micrograms/ml (P less than 0.001), and the ratio of calcitriol/DBP increased from 1.50 +/- 0.14 to 1.94 +/- 0.18 (P less than 0.005), confirming the rise in free calcitriol. Increases in free calcitriol and in calcitriol/DBP ratios were significantly correlated, r = 0.72. Hypocalcemia led to a rapid increase in circulating immunoreactive parathyroid hormone, and to a rise in calcitriol at 24 h. The hypocalcemia-induced rise in total and free calcitriol was similar before and after estrogen, whether expressed as increments or as percent changes. We conclude that estrogen increases circulating levels of biologically active free calcitriol in postmenopausal women, but that a 30-d period of estrogen administration does not apparently improve the renal 1 alpha-hydroxylase response to a PTH challenge.