The effect of endogenous estrogen fluctuation on metabolism of 25-hydroxyvitamin D.

To test the hypothesis that estrogen modulates the metabolism of 25-hydroxyvitamin D (25(OH)D) to 1,25-dihydroxyvitamin D (1,25(OH)2D) and 24,25-dihydroxyvitamin D (24,25(OH)2D), we studied 20 normal premenopausal women at four consecutive weekly intervals during one menstrual cycle. Estrogen stimulation was semiquantitatively defined into baseline, low-grade, or medium-grade categories, based on endogenous estrone and estradiol concentrations. 1,25(OH)2D increased incrementally from baseline levels of 34 +/- 3(SE) pg/ml to 39 +/- 3 pg/ml (P = 0.2) with low-grade estrogen stimulation and to 43 +/- 3 pg/ml (P less than 0.05) with medium-grade estrogen stimulation, while 25(OH)D, 24,25(OH)2D, vitamin D binding protein, parathyroid hormone, calcium, and phosphate did not change. 24,25(OH)2D was correlated to 25(OH)D at baseline (r = 0.65, P less than 0.01) and with low-grade estrogen stimulation (r = 0.62, P less than 0.01), but not with medium-grade stimulation (r = 0.13); these relationships are consistent with the concepts that 25(OH)D is metabolized predominantly to 24,25(OH)2D at low estrogen levels, but not at higher estrogen levels. We conclude that endogenous estrogen elevation promotes formation of 1,25(OH)2D from 25(OH)D, and that it may reciprocally inhibit synthesis of 24,25(OH)2D.

Interaction between parathyroid hormone and endogenous estrogen in normal women.

It has been hypothesized that estrogens conserve bone substance by blocking the resorbing effect of parathyroid hormone (PTH). We evaluated this hypothesis by examining the relation of circulating PTH to endogenous estrogen fluctuation during four quarters of a single menstrual cycle in 20 normal women. The hypothesis predicts that PTH should vary directly with estrogen, since PTH should increase following estrogen elevation to satisfy physiologic demands for calcium. Contrary to the predicted direct variation, PTH remained constant throughout the menstrual cycle despite sharply fluctuating estrogen levels. Furthermore, PTH was negatively associated with estrone during the early follicular (r = -.65, P less than 0.005) and late follicular (r = -.84, P less than 0.0001) phases. We attempted to determine whether this unexpected relationship between estrone and PTH signified a direct physiologic link, by excluding factors which could have spuriously engendered the inverse correlation. Stepwise multiple regression and partial correlation showed that estrone contributed significantly to circulating PTH independent of the effects of dietary calcium, 25-hydroxyvitamin D, serum calcium, 1,25-dihydroxyvitamin D, phosphate, estradiol, progesterone, and body weight. Therefore, it is possible that the inverse correlation between estrone and PTH signified a direct physiologic link, as an artifactual cause for the relationship could not be identified. These data imply that estrone interacts with PTH, but not by blocking PTH-mediated bone resorption. We conclude that estrone is associated with reduced circulating PTH through an as yet undetermined mechanism.