Does DMPA use increase fracture risk in women?
One popular form of birth control for young women is use of the contraceptive injection (depot medroxyprogesterone acetate, DMPA, Depo-Provera, Pfizer, New York City; Medroxyprogesterone Acetate Injectable Suspension, Teva Pharmaceuticals USA, North Wales, PA). In an analysis of national data, one-quarter of women ages 15-24 said they had used the contraceptive shot.1
Results of a new population-based study of women ages 20-44 in the United Kingdom suggest that use of DMPA is associated with an increased risk of fractures.2 Exposure to sex hormones during adolescence plays an important role in the accrual of bone mass; because DMPA prevents pregnancy by inhibiting the secretion of pituitary gonadotropins resulting in anovulation, amenorrhea, and decreased production of serum estrogen, providers are mindful about its impact on young bones.
Researchers at the University Hospital Basel, Switzerland and the Boston University Medical Center in Lexington, MA, evaluated the relationship between long-term use of DMPA, with or without estrogen, and the risk of fractures. They used a case-control analysis of the United Kingdom-based General Practice Research Database, the world's largest computerized database of anonymized longitudinal medical records from primary care. The researchers focused on females ages 20-44 with an incident fracture diagnosis between 1995 and 2008.
For each case and control, scientists looked at the exposure history for DMPA, low-dose MPA alone, or combined oral contraceptives before the index date. They assessed odds ratios (OR) with 95% confidence intervals (CI) of incident fracture in relation to exposure to DMPA or combined oral contraceptives. Adjustments were made for smoking, body mass index, and other potential confounders.
The analysis identified 17,527 incident fracture cases and 70,130 control patients (DMPA exposure: 11% and 8%, respectively). Compared with nonuse, current use of 1-2, 3-9, or 10 or more DMPA prescriptions yielded adjusted OR for fractures of 1.18 (95% CI = 0.93-1.49), 1.36 (95% CI = 1.15-1.60), and 1.54 (95% CI = 1.33-1.78), respectively. Scientists note fracture risk was highest after longer treatment duration (more than 2-3 years), and there was no difference in patients below and above age 30. For users of combined oral contraceptives, the OR were about 1.2
The finding of a possibly slightly increased fracture risk in association with long-term DMPA use fits in well with observations on DMPA effects on bone turnover, says Christoph Meier, MD, professor at the University Hospital Basel and an investigator in the current study. Nevertheless, Meier points out that this study is a retrospective analysis of medical records and not a randomized trial. Due to its design, the investigators could not rule out that certain confounding took place, he explains.
"We did the best we could to rule out such confounding, but we cannot rule out that some residual confounding plays a role," says Meier. "Thus, as interesting as our results are, they should not modify daily practice."
Most fractures in reproductive-age women are caused by trauma, such as motor vehicle accidents, not skeletal fragility, says Andrew Kaunitz, MD, professor and associate chair in the Obstetrics and Gynecology Department at the University of Florida College of Medicine Jacksonville. In addition, as the authors of the current study point out, DMPA users differ in a variety of ways, such as in socioeconomic status and behaviors, from non-users, Kaunitz observes. Such differences can impact risk of traumatic fractures, he notes.
"Notably, this case-control analysis was not able to assess participants' risk of fracture at baseline, prior to initiating DMPA injections," Kaunitz states.
A prospective, short-term study of female military recruits evaluated risk factors for stress fractures during basic training. It found that age, race, alcohol and tobacco use, weight-bearing exercise, lowest adult weight, and corticosteroid use were associated with stress fractures. The study also found an increased risk in white women using DMPA.3 However, this study was limited to women at high risk for fractures and is not applicable to the general population.4
A recent Cochrane review on the subject of fractures in women who have used DMPA shows no randomized controlled trial of DMPA and fracture risk has been performed.5
Weigh risks, benefits
DMPA is widely used by women for whom successful use of a daily or partner-dependent contraceptive is difficult.4 Women initiating DMPA should be thoroughly counseled about the benefits and potential risks of the drug; daily exercise and age-appropriate calcium and vitamin D intake should be encouraged.4
Adding vitamin D and calcium may help in preventing bone loss, says Meier. This could be studied prospectively and might have some clinical relevance, he states.
Remind women that research suggests that at least some of the bone loss experienced as a result of DMPA use is recovered after discontinuation. In fact, a 2010 research article detailing a seven-year, prospective, nonrandomized, multicenter observational study of adolescent females ages 12–18 who initiated and later discontinued DMPA found that bone mineral density loss in teen users is substantially or fully reversible following discontinuation.6
References
- Whitaker AK, Dude AM, Neustadt A, et al. Correlates of use of long-acting reversible methods of contraception among adolescent and young adult women. Contraception 2010; 81:299-303.
- Meier C, Brauchli YB, Jick SS, et al. Use of depot medroxyprogesterone acetate and fracture risk. J Clin Endocrinol Metab 2010. E-pub ahead of print. Doi:10.1210/jc.2010-0032.
- Lappe JM, Stegman MR, Recker RR. The impact of lifestyle factors on stress fractures in female Army recruits. Osteoporos Int 2001; 12:35-42.
- American College of Obstetricians and Gynecologists. Committee Opinion No. 415: Depot Medroxyprogesterone Acetate and Bone Effects. Obstet Gynecol 2008; 112:727-730.
- Lopez LM, Grimes DA, Schulz KF, et al. Steroidal contraceptives: effect on bone fractures in women. Cochrane Database Syst Rev 2009; No. 2. Art. No.: CD006033. Doi: 10.1002/14651858.CD006033.pub3.
- Harel Z, Johnson CC, Gold MA, et al. Recovery of bone mineral density in adolescents following the use of depot medroxyprogesterone acetate contraceptive injections. Contraception 2010; 81:281-291.
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