New guidance underscores DMPA's safety, efficacy in long-term use

Concerns about bone density should not prevent provision or limit use

Concerns about the effects of the contraceptive injection depot medroxyprogesterone acetate (DMPA, Depo-Provera, Pfizer, New York City; Medroxyprogesterone Acetate Injectable Suspension USP, Teva Pharmaceuticals USA, North Wales, PA) on bone mineral density (BMD) should not prevent clinicians from prescribing the method, nor should its use be limited to two years, according to a new committee opinion released by the American College of Obstetricians and Gynecologists (ACOG).1

In November 2004, the Food and Drug Administration (FDA) added a "black box" warning to the drug's labeling to highlight that prolonged use may result in BMD loss. The warning advised that bone loss in women who use Depo-Provera is greater with increased duration of use and may not be completely reversible. The injectable contraceptive should be used as a long-term birth control method (longer than two years) only if other birth control methods are inadequate, the updated label advised.

DMPA has been associated with losses of BMD at the hip and spine of 0.5% to 3.5% after one year of use, and 5.7% to 7.5% after two years.2-5 DMPA's greatest effect on BMD occurs during the first few years of use.5,6 However, BMD has been demonstrated to return to levels at or near baseline at two years after the discontinuation of DMPA.7,8

Women should be thoroughly counseled about the risks and benefits of DMPA so they can make an informed decision about whether it is right for them," says Denise Jamieson, MD, chair of ACOG's Committee on Gynecologic Practice.

"Many women would choose the theoretical risk of future fracture over the very real risk of an unintended pregnancy," says Jamieson. "For example, a teen at high risk of pregnancy, who faces a similar rate of bone loss from either pregnancy or DMPA use, may find the risk worthwhile."

Use affirmed by WHO

The ACOG opinion falls in line with a similar review issued by the World Health Organization in 2005. The international health agency convened a technical consultation to review the complete body of evidence regarding the effects of hormonal contraception on bone mineral density and fracture risk. Guidance issued following the consultation advises:

  • There should be no restriction on the use of DMPA, including no restriction on duration of use, among women ages 18-45 who are otherwise eligible to use the method.
  • Among adolescents (menarche to those below age 18) and women over 45, the advantages of using DMPA generally outweigh the theoretical safety concerns regarding fracture risk. Since data are insufficient to determine if circumstances are similar in long-term use among these age groups, the overall risks and benefits for continuing use of the method should be reconsidered over time with the individual user.9

While a 2005 editorial in the journal Contraception called for the FDA to "consider revising or rescinding the black box warning to reflect current science regarding DMPA use and skeletal health," the FDA has not revised the drug's labeling.10

Put it in perspective

Bone loss in reproductive-age women is not exclusive to DMPA users, the ACOG opinion notes. Adult women show similar rates of temporary bone loss during pregnancy and breastfeeding (2-8% and 3-5%, respectively) when compared with BMD loss sustained by DMPA users (approximately 3-5%).11-12

Teens who use DMPA lose BMD at a time when their BMD typically would increase, which can be a cause of concern, the opinion notes. However, while low BMD is linked to an increased risk of fracture in older women, no studies have linked DMPA-related BMD loss with increased rates of fracture in younger women with a low-fracture risk, the opinion states.1

Shot makes its mark

More than two million American women use DMPA, including approximately 400,000 teens, according to national data.13 With correct and consistent use, the probability of pregnancy is only 0.3%.14

"DMPA has a number of characteristics that make it particularly appealing to certain populations such as adolescents or women who may have a hard time successfully using a daily or partner-dependent method of contraception," says Jamieson. "Some women also prefer it over other methods of contraception because of the privacy that it provides."

Daily exercise and age-appropriate calcium and Vitamin D intake should be encouraged in DMPA users, especially in teens, who often do not get enough calcium. The Institute of Medicine recommended average daily intake of calcium for teens ages 14-18 is 1,300 mg; for women ages 19-50, 1,000 mg.15 While studies have shown that low-dose estrogen supplementation slows bone DMPA bone loss, ACOG does not currently recommend such practice.1 This research, however, also demonstrates that in adult and adolescent women, BMD recovers after DMPA is discontinued, which renders it unlikely that women in either group would benefit from estrogen supplementation.16

In counseling women on DMPA use, be sure to counsel on breakthrough bleeding to help women continue on the method.1 Language suggested by Contraceptive Technology might help explain DMPA's impact on periods:

"DMPA makes a woman's periods less regular, and spotting between periods is fairly common. Eventually most women stop having periods completely. This is not harmful. Do not choose DMPA unless you do not mind having your periods change."13


  1. ACOG Committee Opinion No. 415: Depot Medroxyprogesterone Acetate and Bone Effects. Obstet Gynecol 2008;112:727-730.
  2. Berenson AB, Radecki CM, Grady JJ, et al. A prospective, controlled study of the effects of hormonal contraception on bone mineral density. Obstet Gynecol 2001; 98:576-582.
  3. Ulrich CM, Georgiou CG, Snow-Harter CM, et al. Bone mineral density in mother-daughter pairs: relations to lifetime exercise, lifetime milk consumption, and calcium supplements. Am J Clin Nutr 1996; 63:72-79.
  4. Santelli JS, Abma J, Ventura S, et al. Can changes in sexual behaviors among high school students explain the decline in teen pregnancy rates in the 1990s? J Adolesc Health 2004; 35:80-90.
  5. Clark MK, Sowers MR, Nichols S, et al. Bone mineral density changes over two years in first-time users of depot medroxyprogesterone acetate. Fertil Steril 2004; 82:1,580-1,586.
  6. Scholes D, LaCroix AZ, Ichikawa LE, et al. Injectable hormone contraception and bone density: results from a prospective study. Epidemiology 2002; 13:581-587.
  7. Scholes D, LaCroix AZ, Ichikawa LE, et al. Change in bone mineral density among adolescent women using and discontinuing depot medroxyprogesterone acetate contraception. Arch Pediatr Adolesc Med 2005; 159:139-144.
  8. Kaunitz AM, Miller PD, Rice VM, et al. Bone mineral density in women aged 25-35 years receiving depot medroxyprogesterone acetate: recovery following discontinuation. Contraception 2006; 74:90-99.
  9. World Health Organization. Technical Consultation on the Effects of Hormonal Contraception on Bone Health. Geneva, Switzerland; 2005. Accessed at
  10. Kaunitz AM. Depo-Provera's black box: time to reconsider? Contraception 2005; 72:165-167.
  11. Karlsson C, Obrant KJ, Karlsson M. Pregnancy and lactation confer reversible bone loss in humans. Osteoporos Int 2001; 12:828-834.
  12. Sowers M, Corton G, Shapiro B, et al. Changes in bone density with lactation. JAMA 1993; 269:3,130-3,135.
  13. Mosher WD, Martinez GM, Chandra A, et al. Use of contraception and use of family planning services in the United States: 1982-2002. Adv Data 2004; 350:1-36.
  14. Hatcher RA, Trussell J, Nelson AL, et al. Contraceptive Technology. 19th revised edition. New York: Ardent Media; 2007.
  15. National Institutes of Health. Dietary Supplement Fact Sheet: Calcium. Fact sheet. Accessed at
  16. Association of Reproductive Health Professionals. Labeling Changes for Depot Medroxyprogesterone Acetate. Fact sheet. Accessed at