Bone Loss Is Reversible in Women of All Ages After Discontinuation of Depot Medroxyprogesterone Acetate Injectable Contraception

Abstract & Commentary

Bliss Kaneshiro, MD, MPH, Dr. Kaneshiro is Assistant Professor, University of Hawaii, Honolulu.

Alison Edelman, MD, MPH, Dr. Edelman is Assistant Professor, Assistant Director of the Family Planning Fellowship, Department of Obstetrics & Gynecology, Oregon Health & Science University, Portland, is Associate Editor for OB/GYN Clinical Alert.

Dr. Kaneshiro receives research support from Wyeth Pharmaceuticals and the Society of Family Planning. Dr. Edelman reports no financial relationship to this field of study.

Synopsis: Although data on fracture risk in depot medroxyprogesterone acetate (DMPA) users are lacking, the bone loss that occurs with DMPA use is reversible in women of all ages and is not likely to be a risk factor for low bone density in older women.

Source: Kaunitz AM, et al. Bone density recovery after depot medroxyprogesterone acetate injectable contraception use. Contraception 2008;77:67-76.

Of note, this publication is a review article and not original science. Because of its efficacy and convenience, DMPA has been used by millions of women in the United States and around the world.1 Indeed, contraceptives like DMPA have been credited with decreasing rates of unintended pregnancy in this country, particularly in teens.2

There's no doubt about it, DMPA is an effective birth control method. However, questions have been raised recently about the effects of DMPA on bone mineral density (BMD) and the risk of osteopenia and osteoporosis in older age. To address this issue, the authors conducted a systematic review of the published literature between 1996 and 2006 to evaluate what happens to bone mineral density after DMPA is discontinued. The result is a comprehensive, understandable argument that the bone loss that accompanies DMPA use is reversible. More importantly, the authors demonstrate that DMPA use is not likely to be an important risk factor for low bone density in older women.

Commentary

In November 2004, the FDA required that a "black box warning" be added to the DMPA package labeling. This warning stated that prolonged use of DMPA may result in significant loss of BMD, the loss is proportional to the amount of time on DMPA, and the decrease may not be completely reversible. The warning went on to state that women should use DMPA for more than 2 years only if other contraceptive methods are "inadequate."3

The suggested effect of DMPA on skeletal health is disturbing. Of particular concern are two groups, adolescents, who have not yet attained their peak bone mass, and perimenopausal women, who may be starting to lose bone mass.4 On the other hand, many questioned whether the FDA's warning was based on the best available science. Regardless, there are anecdotal reports of clinicians changing their practice. Some clinicians no longer permitted their patients to use DMPA for more than 2 years. Others mandated that DMPA users (even healthy teenagers!) have dual X-ray absorptometry performed.

Kaunitz and colleagues sought to sort out these issues with this comprehensive review of the literature. In this review of 41 studies, Kaunitz outlined many of the controversies in the DMPA and bone mineral density debate and came to the following conclusions:

  1. Studies examining the effect of DMPA use on bone mineral density in postmenopausal former users of DMPA are sparse and do not suggest an impact of DMPA on postmenopausal bone mineral density levels.
  2. Bone mineral density returns to levels at or near baseline in premenopausal women who discontinue DMPA.
  3. Bone mineral density loss is reversible after discontinuation of DMPA in adolescents.
  4. Bone mineral density loss is reversible after treatment with DMPA for endometriosis.

Many, including these authors, have equated DMPA use to lactation. Lactating women demonstrate a decrease in bone mineral density of 4-6% over 6 months when compared to nonlactating women.5,6 No one would ever dream of discouraging postpartum women from breastfeeding. For many women, preventing an unintended pregnancy is as important as breastfeeding. For some, it is more important. With seemingly equivalent risks, skeletal health concerns should not restrict initiation or continuation of DMPA.

However, it is important to talk to your patients about DMPA and bone mineral density. Anyone who cares for young women knows that shortly after receiving their injection, they will look on-line at what the internet has to say about the medications they take. Anyone who checks on-line will see that the issue of bone mineral density in DMPA users has been raised and it is better to counsel patients before they call your office in a state of panic.

The authors were clear to outline that the most important question, the clinical significance of an apparent temporary decrease of bone mineral density in DMPA users is unknown. There are no published studies examining the risk of osteoporosis and the subsequent risk of fracture in DMPA users. Thus, as always, more studies are needed to ultimately find an answer, but this review provides a good indication that bone mineral density loss is reversible in DMPA users.

References

  1. Mosher WD, et al. Use of contraception and use of family planning services in the United States: 1982-2002. Adv Data 2004:1-36.
  2. Westhoff C. Depot-medroxyprogesterone acetate injection (Depo-Provera): A highly effective contraceptive option with proven long-term safety. Contraception 2003;68:75-87.
  3. FDA Talk Paper. Available at: www.fda.gov/bbs. Accessed Sept. 11, 2008.
  4. Kaunitz AM, et al. Bone density recovery after depot medroxyprogesterone acetate injectable contraception use. Contraception 2008;77:67-76.
  5. Kalkwarf HJ, Specker BL. Bone mineral loss during lactation and recovery after weaning. Obstet Gynecol 1995;86:26-32.
  6. Hayslip CC, et al. The effects of lactation on bone mineral content in healthy postpartum women. Obstet Gynecol 1989;73:588-592.