Sex hormones and quantitative ultrasound parameters at the heel in men and women from the general population
CONTEXT There is limited information on the association between sex hormones and bone loss in older men. OBJECTIVE Our objective was to determine the longitudinal association between sex steroid hormones and bone mineral density (BMD). DESIGN AND SETTING We conducted a prospective study of 5995 men aged at least 65 yr old at six U.S. clinical centers. PARTICIPANTS Sex steroid hormones were measured in a random sample of 1602 men. After exclusions, 1238 men were included in cross-sectional analyses and 969 in longitudinal analyses. Baseline sex hormones were measured using liquid chromatography-mass spectrometry. Bioavailable (Bio) estradiol (BioE2) and testosterone (BioT) were calculated from mass action equations. SHBG was measured using chemiluminescent substrate. MAIN OUTCOME MEASURES BMD of the total hip, measured at baseline and once or twice afterward over 4.6 yr of follow-up, was evaluated. RESULTS The annualized percent change in hip BMD increased with decreasing BioE2 (P trend = 0.03). Men with the lowest BioE2 (<39.7 pmol/liter) compared with the highest BioE2 (> or =66.0 pmol/liter) experienced 38% faster rate of BMD loss (P < 0.05). There was no association between BioT and hip BMD loss. Men with lowest BioE2, lowest BioT, and highest SHBG experienced a 3-fold faster rate of BMD loss compared with men with higher levels (P = 0.02). A threshold effect of SHBG was observed; the rate of hip BMD loss increased in men with SHBG of 49-60 nM. CONCLUSIONS Low BioE2 and high SHBG levels were associated with lower BMD and faster hip BMD loss. The combination of low BioE2, low BioT, and high SHBG was associated with significantly faster rates of BMD loss.