Depot medroxyprogesterone acetate (DMPA) is a progestin-only, hormonal contraceptive that is extremely effective, obviates the need for daily or weekly compliance, and can be used privately. DMPA is very appealing for the adolescent contraceptive user. Despite its many advantages, DMPA continuation rates are low in adolescents. Side effects, namely weight gain and bone mineral density (BMD) loss, are major barriers to prolonged DMPA use. The research questions in this study are whether higher circulating levels of medroxyprogesterone acetate (MPA) are related to weight gain and BMD loss and whether lower doses of DMPA offer an improved side effect profile. Specific Aim: We will assess measures of weight gain and BMD loss on DMPA and their association to MPA drug exposure. A clinical study on 45 adolescents age 12-21 years, enrolled into three DMPA dose cohorts (150, 104, and 75 mg) will be performed to determine a dose of DMPA that mitigates weight gain and BMD loss while maintaining contraceptive efficacy. Our long-term objectives are to establish a framework for early identification of risk of DMPA side effects and use of pharmacokinetic-pharmacodynamic parameters to individualize DMPA dosing in the future.