OBJECTIVE We studied the effect of levothyroxine (L-T(4)) suppressive therapy on bone mineral density (BMD) in pre-menopausal women with total thyroidectomy and radioactive iodine ((131)I) ablation therapy post-operatively for differentiated thyroid cancer (DTC). METHODS We prospectively studied 26 athyroid pre-menopausal women (median age 39 years, range 28-48 years) receiving suppressive L-T(4) therapy postoperatively for 48 months. BMD was measured by dual energy X-ray absorptiometry (DEXA) at the femoral neck, femoral trochanter and Ward's triangle, before (basal) and during (12th and 48th month) the follow-up period. None of the women gave a medical history that could possibly affect bone metabolism. Patients were free of thyroid cancer in clinical and laboratory examinations at the time of the study. Paired t-test was used for comparisons among BMD measurements during the suppressive therapy. RESULTS There were statistically significant decreases of BMD at all measured regions during (12th and 48th month) L-T(4) suppressive therapy. The overall decreases in BMD at the femoral neck, femoral trochanter and Ward's triangle were 7.5%, 10.9% and 3.4%, respectively, at the end of the follow-up period. The coefficient of variation (CV) of all BMD measurements was around 10%, showing a rather homogenous group of patients. Our patients had a statistically significant decrease in their body mass index (BMI) and weight at the end of the follow-up period. However, there was no significant correlation between the decrease in BMI and BMD. Patients did not experience significant adverse effects from L-T(4) suppressive therapy during the study. CONCLUSIONS L-T(4) suppressive therapy for at least 1 year in pre-menopausal women with DTC causes a reduction in BMD of the femoral neck, femoral trochanter and Ward's triangle.