Subcutaneous DMPA vs. intramuscular DMPA: a 2-year randomized study of contraceptive efficacy and bone mineral density

Contraception. 2009 Jul;80(1):7-17. doi: 10.1016/j.contraception.2009.02.005. Epub 2009 Mar 27.


Background: A formulation of depot medroxyprogesterone acetate (DMPA) has been developed that allows subcutaneous injection (104 mg/0.65 mL; DMPA-SC) and achieves highly effective contraception with a similar tolerability profile to intramuscular DMPA (150 mg/mL; DMPA-IM).

Study design: This randomized, evaluator-blinded study was designed to compare efficacy, safety, and user satisfaction in women receiving DMPA-SC (n=266) or DMPA-IM (n=268) for 2 years with an option to continue for a third year. The primary objectives were to evaluate bone mineral density (BMD) changes and contraceptive efficacy after 2 years.

Results: A total of 225 women completed the first 2 years of this study (DMPA-SC, n=116; DMPA-IM, n=109). After 2 years of DMPA use, BMD loss was marginally smaller in the DMPA-SC group than in the DMPA-IM group at both the total hip (-3.3% and -3.6%, respectively) and lumbar spine (-4.3% and -5.0%, respectively). In those women who received DMPA during the third year, there were no statistically significant differences in BMD loss between DMPA-SC and DMPA-IM groups at the end of Year 3. Recovery of BMD was observed in the small subpopulation of women who had discontinued DMPA-SC or DMPA-IM after the second year. The 2-year treatment-failure cumulative pregnancy rate was 0% in the DMPA-SC group and 0.8% (95% confidence interval, 0.00-2.37%) in the DMPA-IM group (life-table method). Adverse events were similar in the two groups except that injection site reactions were more common in the DMPA-SC group.

Conclusion: DMPA-SC is an effective and well-tolerated contraceptive option, providing comparable efficacy and BMD safety to DMPA-IM.

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Bone Density / drug effects*
  • Contraceptive Agents, Female / administration & dosage*
  • Contraceptive Agents, Female / adverse effects*
  • Contraceptive Agents, Female / pharmacokinetics
  • Delayed-Action Preparations / administration & dosage
  • Delayed-Action Preparations / adverse effects
  • Estradiol / blood
  • Female
  • Humans
  • Injections, Intramuscular
  • Injections, Subcutaneous
  • Medroxyprogesterone Acetate / administration & dosage*
  • Medroxyprogesterone Acetate / adverse effects*
  • Medroxyprogesterone Acetate / pharmacokinetics
  • Metrorrhagia / chemically induced
  • Patient Satisfaction
  • Pregnancy
  • Young Adult


  • Contraceptive Agents, Female
  • Delayed-Action Preparations
  • Estradiol
  • Medroxyprogesterone Acetate