Effect of Estrogen on Calcium Absorption and Serum Vitamin D Metabolites in Postmenopausal Osteoporosis*

Osteoporotic women have decreased calcium absorption and decreased serum 1,25-dihydroxyvitamin D [1,25-(OH)2D] and are usually in negative calcium balance. Estrogen therapy improves calcium balance in patients with postmenopausal osteoporosis. In birds, estrogen administration increases the conversion of 25-hydroxyvitamin D (25OHD) to 1,25-(OH)2D. To determine if estrogen therapy affects vitamin D metabolism in human subjects, we studied 21 osteoporotic women before and after 6 months of treatment. We compared groups treated with either placebo (9 patients) or conjugated equine estrogen (1.2-2.5 mg/day; 12 patients). Fractional calcium absorption (mean +/- SE) was unchanged after treatment with placebo (0.51 +/- 0.03 to 0.52 +/- 0.01) but increased after treatment with estrogen (0.53 +/- 0.02 to 0.65 +/- 0.04; P < 0.005). The increase after estrogen was similar to the increase observed in 10 additional osteoporotic women treated for 6 months with a small dose of 0.5 microgram/day 1,25-(OH)2D (0.54 +/- 0.03 to 0.68 +/- 0.04; P < 0.005). Serum 1,25-(OH)2D was unchanged after treatment with placebo (27.5 +/- 1.3 to 27.6 +/- 1.7 pg/ml) but increased after treatment with estrogen (23.6 +/- 2.7 to 33.2 +/- 3.7 pg/ml; P < 0.005). Serum immunoreactive parathyroid hormone (PTH) increased (23.0 +/- 4.2 to 32.7 +/- 4.6 microliter eq/ml; P < 0.05) after estrogen but not after placebo treatment. After treatment with estrogen, the increases in serum immunoreactive PTH and serum 1,25-(OH)2D were correlated (r = 0.68; P < 0.05), and the increases in serum 1,25-(OH)2D and calcium absorption were highly correlated (r = 0.89; P < 0.001). We conclude that estrogen treatment increases calcium absorption in postmenopausal osteoporosis by increasing serum 1,25(OH)2D. This effect appears to be mediated indirectly through stimulation of renal 1 alpha-hydroxylase by increased serum PTH.