The Truth Behind the New Depo Label

by Amy Allina
In November 2004, the Food and Drug Administration (FDA) announced that it was adding a “black box” warning to the label of the contraceptive shot, Depo-Provera. The new label highlights research showing that Depo-Provera may cause loss of bone mineral density (BMD) and cautions women not to use Depo for longer than two years unless other birth control methods are 'inadequate'.
For decades, women’s health advocates have raised concerns about Depo-Provera’s safety. Over time, research has laid to rest some, but not all, of the questions about the drug’s effects. One positive research finding is that, despite concerns based on animal studies, accumulating evidence indicates that Depo does not increase women's risk of breast cancer.1
Uncertainty remains, however, about Depo’s effect on the bone strength of women who use it, particularly long-time Depo users. As early as 1992, when the FDA approved Depo in the U.S., preliminary research indicated that Depo users experienced BMD loss. The FDA responded by mandating post-approval studies to examine this effect and, last year, Pfizer (which now owns Depo-Provera) submitted data from that research to the FDA. After reviewing the research, the FDA changed the Depo label and added the 'black box' warning.
Loss of Bone Mineral Density by Depo-Provera Users
The research that Pfizer submitted included results from two studies (one of adults and one of adolescents) that monitored three BMD measurements: spine, total hip and the area where the femur meets the hip. The studies followed women for up to five years of Depo-Provera use and two years of monitoring after treatment stopped. Because very few of the women used Depo over the entire five years, conclusions about the effects of long-term use are based on the experiences of a small number of women. Nonetheless, the results are clear and significant.
The research found that women who use Depo-Provera may lose bone mineral density, placing them at increased risk of getting osteoporosis and breaking a bone. The loss of BMD is greater with longer use of Depo, although most bone loss occurs within the first few years. Women who continued to use Depo for the study’s full five years lost between five and six percent of BMD, compared to their BMD measurements before starting Depo.
Partial Reversal After Depo-Provera Discontinuation
Most of the adult women studied experienced a partial reversal of their bone loss after discontinuing Depo, and some women experienced a complete reversal of their bone loss. In adults, BMD measurements for spine and total hip showed a strong trend toward complete reversal in the two years of post-Depo monitoring included in the study, but BMD loss at the femoral neck persisted to a greater degree. Since the femoral neck is a vulnerable site for hip fracture, continued low BMD at that location might be cause for concern. Furthermore, it is not clear whether some women may have experienced bone loss with no reversal after they stop using Depo. The studies cannot rule out the possibility that Depo-related bone loss may make women more likely to develop osteoporosis later in life. Further research to determine who is likely to experience irreversible bone loss will be critically important to help women make decisions about what contraceptive to use.
The issue of BMD loss and recovery is particularly important for adolescents. The U.S. Surgeon General’s report on bone health notes that adolescent women 'experience their most rapid rate of bone growth during puberty, and by the end of puberty they have almost achieved peak mass.'2 Preliminary data from the adolescent study show that teens had partial recovery of the BMD lost during Depo use. Partial recovery may not be enough to protect the future bone health of these teenage women, however. Healthy teens who do not use Depo experience major increases in bone density during adolescence.
Earlier this year, we learned a little more about what happens to the bones of teens using Depo from a study funded by the National Institutes of Health (NIH).3 The NIH research confirms that bone loss is a concern for adolescents using Depo but provides reassurance about recovery after discontinuation. The study found that women 14-18 who used Depo experienced enough BMD loss that it could significantly raise their risk of experiencing a bone fracture. Teens who stopped using Depo, however, had BMD measurements at spine, hip and whole body 12 months or more after discontinuing that were 'at least as high as those of comparison women' who had not been exposed to the drug.
Health Communication—Or Politically Motivated Attack?
The National Women’s Health Network (NWHN) and other women’s health advocates that pushed for research to answer the outstanding questions about Depo’s safety are encouraged to finally have definitive information about the concerns we raised over 10 years ago, and affirm the importance of communicating this information to women.
Nonetheless, like other reproductive rights advocates, NWHN is concerned about the FDA’s motivation for taking this action. The FDA’s recent track record of manipulating and suppressing scientific data for political ends—and the Bush administration’s track record of attacking family planning—inevitably raise questions about motivations for the label change. In particular, reproductive health advocates question the decision to use a 'black box' warning, which is the FDA’s severest label warning and is commonly (although not exclusively) used for life-threatening conditions. Is this a genuine effort to protect women’s health by sharing new scientific evidence about the effects of Depo Provera? Or is it yet another a politically motivated attack on contraception using science as a smokescreen for the Administration’s anti-choice and anti-family planning agenda?
Unfortunately, doubts about the reliability of Bush’s FDA may undermine women’s faith in new information about Depo-Provera’s negative effects on BMD.
Weighing Risks and Benefits
As a long-acting, hormonal contraceptive method, Depo-Provera has both advantages and disadvantages which every woman must weigh in light of her own life circumstances and health status. The latest data give new reason for caution about Depo use by adolescents and women with existing risk factors for osteoporosis (i.e., metabolic bone disease, chronic alcohol/tobacco use, anorexia nervosa, and chronic use of anticonvulsants or corticosteroids) because these factors also reduce BMD. Women who are potential Depo Provera users must consider whether the method offers enough benefit to offset the added risk it may pose to their health.
This article is adapted from NWHN’s new fact sheet on “Depo-Provera and Bone Mineral Density,” available on our website.
Amy Allina is NWHN’s Director of Programs.
REFERENCES
1. Shapiro S, Rosenberg L, Hoffman M et al. Am J Epidemiol 2000; 151(4):396-403.
2. U.S. Department of Health and Human Services (HHS). Bone Health and Osteoporosis: A Report of the Surgeon General. Washington, DC: HHS, 2004.
3. Change in bone mineral density among adolescent women using and discontinuing depot medroxyprogesterone acetate contraception. Scholes D, LaCroix AZ, Ichikawa LE, Barlow WE, Ott SM. Arch Pediatr Adolesc Med. 2005; 159: 139-144.