Bone Mineral Density and Weight Changes in Adolescents Randomized to 3 Doses of Depot Medroxyprogesterone Acetate

Study Objective To assess the association between medroxyprogesterone acetate exposure and bone mineral density (BMD) loss and weight change in adolescents. Design Forty-eight-week prospective, randomized trial conducted May 2012-April 2014. Setting Recruitment occurred in the general community and outpatient clinics in central Ohio. Participants Self-referred sample of 34 female adolescents aged 12-21 years initiating depot medroxyprogesterone acetate (DMPA). Interventions Randomization to 1 of 3 DMPA doses (150, 104, or 75 mg) given intramuscularly every 12 weeks for 48 weeks. Main Outcome Measures Absolute and percent change in BMD from 0-48 weeks at the L1-L4 lumbar spine, total hip, and femoral neck; absolute and percent change in weight at 48 weeks. Results DMPA dose was associated with medroxyprogesterone acetate exposure as evidenced by a direct relationship (P < .001) between dose group and area under the concentration time curve. At 48 weeks, no significant BMD decreases were seen in the 75 mg dose group. The 104 and 150 mg dose groups experienced significant (P < .01) decreases in L1-L4 lumbar spine BMD (3.1% and 4.0%, respectively). The 150 mg group also had significant (P < .05) decreases in total hip (3.0%) and femoral neck (4.0%) BMD. No group differences in weight change were observed. No pregnancies occurred in any DMPA dose group. Conclusions Our data provide evidence of a dose-response relationship between DMPA and BMD loss. Intramuscular DMPA doses less than 150 mg can decrease risk of BMD loss in adolescents. The risk/benefit ratio of lower-dose DMPA should be further investigated in larger and more diverse adolescent populations.