Assessment of the role of 17β-oestradiol in bone metabolism in men:: does the assay technique matter?: The MINOS study

OBJECTIVE 17beta-Oestradiol (17beta-E2), mainly its bioavailable fraction (bio-17beta-E2), is a determinant of bone mineral density (BMD) and bone remodelling in men. As direct measurement of bio-17beta-E2 is time-consuming, we compared the value of directly measured bio-17beta-E2 and of calculated bio-17beta-E2 and free 17beta-E2 by studying their association with BMD and markers of bone turnover in a cohort of men (MINOS). DESIGN A cross-sectional study in which the association between BMD and bone markers, on the one hand, and serum levels of 17beta-E2, on the other, was analysed according to the levels of measured and calculated bio-17beta-E2 and free 17beta-E2 in a cohort of men. SUBJECTS Men from the MINOS cohort including 87 men aged 19-45 to establish the reference control normal range of hormones and 637 men aged 50-85 (studied group). MEASUREMENTS Total 17beta-E2, testosterone, SHBG and albumin were measured by standard methods. bio-17beta-E2 was directly measured after the precipitation of SHBG by ammonium sulfate. bio-17beta-E2 and free 17beta-E2 were calculated using serum SHBG and albumin levels as described by Sodegard et al. (J. Steroid Biochem., 16 (1982) 801). RESULTS Calculated bio-17beta-E2 and free 17beta-E2 were correlated with measured bio-17beta-E2 and between themselves (r = 0.90-1.00, P < 0.0001). Calculated bio-17beta-E2 and free 17beta-E2 disclosed a similar association with BMD (difference between lowest and highest quartiles of 17beta-E2: 2.6-6.8%, P < 0.05-0.005) to that of measured bio-17beta-E2 (3.6-6.1%, P < 0.005-0.001). The association between bone markers levels and measured vs. calculated 17beta-E2 were also similar. Predictive accuracy for lowered BMD and elevated levels of biochemical bone markers (evaluated using receiver operating characteristics) was relatively low (area under curve -0.582 to 0.709) but similar for different forms of bioavailable and free 17beta-E2. CONCLUSIONS In elderly men, the concentrations of bioavailable and free 17beta-E2, calculated using equations including either the measured albumin concentration or the constant albumin concentration of 43 g/l, can be used, at least in clinical studies, instead of the bio-17beta-E2 concentrations measured after ammonium sulfate precipitation.