Comparison of the long-term effects of oral estriol with the effects of conjugated estrogen, 1-alpha-hydroxyvitamin D3 and calcium lactate on vertebral bone loss in early menopausal women.

We investigated the long-term effects of oral estriol (E3) on bone mineral density (BMD) at the lumbar spine and biochemical indices of bone turnover in early menopausal women. We studied 64 healthy early menopausal women who were treated for 24 months with 2.0 mg E3 plus 2.5 mg medroxyprogesterone acetate daily (E3 group, n = 15), 0.625 mg of conjugated estrogen plus 2.5 mg medroxyprogesterone acetate daily (CE group, n = 19), 1.0 microgram 1-alpha-hydroxyvitamin D3 daily (D3 group, n = 13), or 1.8 g calcium lactate containing 250 mg of elemental calcium daily (Ca group, n = 17). The BMD at the third lumbar vertebra was determined by quantitative computed tomography, and serum levels of osteocalcin (OC) and total alkaline phosphatase (Alp), as well as urinary ratios of calcium-to-creatinine (Ca/Cr) and hydroxyproline-to-creatine (Hyp/Cr), were evaluated at baseline and every 6 months. After 24 months of treatment, the BMD decreased significantly by 12 +/- 4.5% (mean +/- S.E.) in the D3 group and 14 +/- 2.5% in the Ca group, but not in the E3 group (-4.1 +/- 4.8% from baseline) and in the CE group (-0.9 +/- 3.2% from baseline). The serum levels of Alp and OC decreased or remained unchanged in the E3 and CE groups, but increased in the D3 and Ca groups. The urinary Ca/Cr was decreased in the E3 and CE groups, but not in the D3 and Ca groups. The urinary Hyp/Cr decreased in the CE group, was unchanged in the E3 and D3 groups, and increased in the Ca group. Uterine bleeding occurred less frequently in the E3 than in the CE group (2.4 +/- 4.2 versus 13.1 +/- 14.8 days/person per year, P < 0.001). The bone-preserving effect of 2.0 mg of oral E3 was comparable to that of 0.625 mg of conjugated estrogen and was superior to that of 1.0 microgram 1-alpha-hydroxyvitamin D3 and 1.8 g Ca. Our findings suggest that a reduction in bone turnover in the E3 group may have contributed to the preservation of bone.