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

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Abstract
Osteoporotic women have decreased Ca absorption and decreased serum 1,25-dihydroxyvitamin D [1,25-(OH)2D] and are usually in negative Ca balance. Estrogen therapy improves Ca 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, 21 osteoporotic women were studied before and after 6 mo. of treatment. Groups treated with either placebo (9 patients) or conjugated equine estrogen (1.2-2.5 mg/day; 12 patients) were compared. Fractional Ca 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 mo. with a small dose of 0.5 .mu.g/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 .mu.eq/ml; P < 0.05) after estrogen but not after placebo treatment. After estrogen treatment 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 Ca absorption were highly correlated (r = 0.89; P < 0.001). Estrogen treatment evidently increases Ca 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.