Changes in vitamin D metabolism during natural and medical menopause

Thirty-nine women were studied longitudinally for 3 yr, during which period 10 women passed a natural menopause. Vitamin D metabolites were determined every 3 months in these 10 women. The same variables were studied in 42 premenopausal women with endometriosis treated for 6 months with nafarelin acetate (a LHRH agonist) given alone in a dose of 200 or 400 micrograms or in a dose of 400 micrograms combined with 1.2 mg norethisterone (NET)/day and followed-up for a further 6 months. No changes were seen in 1,25-dihydroxyvitamin D [1,25-(OH)2D], vitamin D-binding protein, or the free index of 1,25-(OH)2D during the natural menopause. A small increase was found in 25-hydroxyvitamin D [25OHD] and 24,25-(OH)2D3 after correction for seasonal variation. All three nafarelin groups had a significantly decreased free index of 1,25-(OH)2D, which returned to the baseline value on withdrawal of the treatment. Serum 25OHD and 24,25-(OH)2D3 were increased at 6 months and thereafter decreased to baseline values. These changes were still visible after correction for seasonal variation. Vitamin D-binding protein showed a small transient increase in the nafarelin plus NET group, but was unchanged in the other two groups. The 24-h urinary excretion of calcium increased significantly in the groups receiving nafarelin alone, whereas it remained unchanged in the nafarelin plus NET group. We conclude that detectable changes in 1,25-(OH)2D do not occur in natural menopause. Treatment with LHRH agonists produces a significant decrease in serum 1,25-(OH)2D, which does not seem to be dependent on increased bone resorption. This suggests that LHRH agonists may induce a change in other pituitary hormones involved in vitamin D regulation.