The bone density (BD) of 72 women using depot-medroxyprogesterone acetate (DMPA) for at least 1 year was compared with that of 64 women who were not users of hormonal contraceptives. The BD of lumbar spine, femoral neck, Ward's triangle, and trochanter was measured by dual energy X-ray absorptiometry (DEXA-LUNAR DPX). Estradiol (E2) concentrations were measured by radioimmunoassay (RIA). The mean age of DMPA users and nonusers was 31.8 and 31.1 years, respectively. Mean E, was 55.7 pg/mL for users and 149.9 pg/mL for controls (p < 0.001). The BD was significantly lower for DMPA users than for controls in all sites (p < 0.01). In addition, young adult T-scores in the lumbar spine were significantly lower among DMPA users than in controls (p < 0.01). Differences were maintained in a subsample of 47 women per group paired by age and body mass index (BMI). Multiple regression analysis showed that older age, lower BMI, and longer amenorrhea were associated with lower BD in the femoral neck, whereas lower BMI and use of DMPA were associated with lower BD in the lumbar spine.58351-5