A randomized controlled trial of estrogen replacement therapy in long-term users of depot medroxyprogesterone acetate.

Long-term use of the injectable contraceptive depot medroxyprogesterone acetate (DMPA, Depo-Provera) is associated with a reduction in bone mineral density (BMD), particularly in the lumbar spine. The cause of DMPA-associated bone loss is not known, but the relative estrogen deficiency induced by DMPA use could be responsible. We have undertaken a randomized, double-blind controlled trial of oral estrogen replacement therapy in 38 premenopausal women (mean age 37) with a minimum 2 yr DMPA use who had a below average baseline lumbar spine BMD (T score ≤ 0). Nineteen women were allocated to receive conjugated estrogens (0.625 mg/d orally) and 19 to receive a matching placebo. All continued with regular DMPA injections throughout the study. Areal bone density was measured by dual energy x-ray absorptiometry at the lumbar spine, femoral neck, and total body sites every 6 months for 2 yr; the main outcome measure being the change in areal BMD at the lumbar spine. At baseline, the two groups were well matched f...