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Depot medroxyprogesterone acetate (DMPA) injectable contraception may decrease bone density and increase the risk for osteoporosis in later life. Prospective data are scarce, especially of the effects of DMPA discontinuation on bone.Between 1994 and 1999, we conducted a population-based prospective cohort study among women enrollees of a Washington State health maintenance organization. We enrolled 457 nonpregnant women, ages 18–39 years (183 DMPA users and 274 non-users). Bone density was measured by dual-energy x-ray absorptiometry every 6 months for 3 years.Bone density decreased notably among DMPA-exposed women at the spine (adjusted mean bone density was −0.0053 gm/cm2 for DMPA users compared with +0.0023 gm/cm2 for non-users for each 6-month interval) and total hip (−0.0060 compared with −0.0002 gm/cm2). This represents an annualized mean rate of change at the spine of −0.87% compared with +0.40% and, at the hip, −1.12% compared with −0.05%. Discontinuers of this method (N = 110) showed sizable increases in bone density over comparison women (for each 6-month interval, adjusted mean spine bone density was +0.0067 gm/cm2 compared with +0.0023 gm/cm2, respectively; adjusted mean hip bone density was +0.0035 compared with −0.0002 gm/cm2). Estimated annualized mean rates of change were +1.41% compared with +1.03% at the spine and +0.40% compared with −0.05% at the hip. After 30 months, mean bone density for discontinuers was similar to that of non-users.In this study, DMPA use was strongly associated with bone density loss. Substantial postdiscontinuation recovery of bone provides evidence that the effects may be largely reversible.