Family planning programs that offer depot medroxyprogesterone acetate (DMPA) cannot be indifferent to the risk of lowered bone density. A study conducted at the Family Planning Clinic of the State University of Campinas (Sao Paulo, Brazil) compared bone densities in 72 women who had been using DMPA for at least 1 year (mean duration, 42 months) and 64 regularly menstruating nonusers. Mean age was 31 years in both groups; there were no significant differences between the 2 groups in terms of ethnicity, body mass index (BMI), or smoking. Mean serum estradiol concentrations were 55.7 +or- 40.5 pg/ml for DMPA users and 149.9 +or- 88.2 pg/ml for nonusers (p 0.001). The mean length of amenorrhea was 26.5 +or- 23.8 months among DMPA users. The mean bone density in DMPA users was significantly lower than that of controls at all sites evaluated (i.e., lumbar spine, femoral neck, Ward's triangle, and trochanter). 38 DMPA users, compared with only 17 controls, had a T-score in the lumbar spine lower than -1 standard deviation (p = 0.014). Multiple regression analysis identified BMI and DMPA use as variables significantly associated with bone density in the lumbar spine; in the femoral neck, these variables were BMI, age, and length of amenorrhea. Periodic bone densitometry should be considered for women over 40 years of age with low BMI who have more than 2 years of continuous amenorrhea.