More research emerges on DMPA and bone health
New data from a long-term cohort study comparing bone mineral densities (BMD) in adult users and nonusers of the injectable contraceptive depot medroxyprogesterone acetate (DMPA, Depo-Provera, Pfizer, New York City) indicate that while bone mineral density declines in current DMPA users, it is followed by substantial recovery after discontinuation.1
The data presented at the May 2005 annual meeting of the Washington, DC-based American College of Obstetricians and Gynecologists represent a large, not yet published, long-term cohort study mandated by the Food and Drug Administration (FDA) upon the 1992 approval of the drug, says co-author Andrew Kaunitz, MD, professor and assistant chair in the obstetrics and gynecology department at the University of Florida Health Science Center/Jacksonville.
As has been found by other researchers,2-4 the new study indicates loss of BMD of approximately 1%-2% annually during DMPA use, with slower loss after that and recovery following discontinuation of injections. Investigators followed users’ BMD for almost two years after contraceptive discontinuation; complete recovery of BMD was not found at all skeletal sites assessed, states Kaunitz.
Clinicians have been taking a hard look at DMPA use following the FDA’s late 2004 addition of a "black box" warning to the drug’s labeling to highlight that prolonged use may result in the loss of bone mineral density. According to the revised labeling, 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. Women who continue to use Depo-Provera past the two-year mark should have their BMD evaluated, according to the labeling.
Kaunitz points to research findings that indicate that BMD is comparable in former and never users following discontinuation of DMPA.5-7
"My speculation is that if we had been able to follow BMD for three or more years following DMPA discontinuation, it is likely that complete recovery — as others have shown — would have been documented," states Kaunitz.
In the open-label, prospective, matched cohort study, DMPA users were compared to a cohort using nonhormonal contraception. Women were matched for race and current smoking status. Users in the DMPA group received injections every 12 weeks. The treatment phase ran up to 240 weeks, with up to 96 weeks in the post-treatment follow-up phase.
The researchers set outcome measures to record the percent change from screening in BMD of lumbar spine and hip at after up to 240 weeks (4.6 years) of treatment and after up to 96 weeks (1.8 years) of post-treatment follow-up.
At week 240 of treatment, investigators noted significantly greater decrease from baseline in BMD in the DMPA group compared to the nonhormonal group. However, at 96 weeks post-treatment, differences remained statistically significant, but recovery was observed.1
Depo-Provera is a popular form of contraception. Among females who received services in Title X-funded clinics during 2003, 16% relied on the contraceptive injection as their primary method of birth control.8 Use of the drug has contributed to the declines in unintended pregnancy and abortion in adult women and teens,9 reports Kaunitz.
Practitioners should recognize that the new FDA labeling does not mandate bone density testing for Depo-Provera users. It also does not mean that the drug cannot be used for more than two years, he states.
"The clinical implications, if any, of BMD changes during use of DMPA use should be weighed against this contraceptive’s efficacy, convenience, and safety," states Kaunitz.
The findings reported by Kaunitz of the changes in BMD with long-term treatment with DMPA and the return toward or to pre-treatment values upon discontinuation of treatment mimic the transient, reversible loss of bone density that occurs with breast-feeding and that is not associated with an increase in fracture risk in later life, says Michael McClung, MD, director of the Oregon Osteoporosis Center in Portland.
The relationship between BMD values and fracture risk means something very different in otherwise healthy premenopausal women compared to older postmenopausal women, McClung says.
"It is my opinion that the BMD changes seen with DMPA in otherwise healthy premenopausal women, whose risk of fractures is very low, are of little clinical consequence and do not warrant the concern that has accompanied the addition to the product label for DMPA of the black box warning about those changes," he says. "Since measurement of BMD would not affect clinical management, BMD testing in women receiving DMPA is not warranted in the absence of other risk factors, since it will not influence clinical practice."
References
- Kaunitz AM, Kipersztok S. Evaluation of bone mineral density recovery following discontinuation of DMPA-IM contraception. Presented at the American College of Obstetricians and Gynecologists Annual Clinical Meeting. San Francisco; May 2005.
- Kaunitz AM. Injectable contraception — New and existing options. Obstet Gynecol Clin North Am 2000; 27:741-780.
- Banks E, Berrington A, Casabonne D. Overview of the relationship between use of progestogen-only contraceptives and bone mineral density. BJOG 2001; 108:1,214-1,221.
- Westhoff CL. Depot-medroxyprogesterone acetate injection (Depo-Provera): A highly effective contraceptive option with proven long-term safety. Contraception 2003; 68:75-87.
- Petitti DB, Piaggio G, Mehta S, et al. Steroid hormone contraception and bone mineral density: A cross-sectional study in an international population. The WHO Study of Hormonal Contraception and Bone Health. Obstet Gynecol 2000; 95:736-744.
- 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.
- Scholes D, LaCroix AZ, Ichikawa LE, et al. Injectable hormone contraception and bone density: Results from a prospective study.Epidemiology 2002; 13:581-587.
- Golden AL. OPA Program Instruction Series, OPA 05-01: Updated safety information for Depo-Provera Contraceptive Injection (medroxyprogesterone acetate injectable suspension). Letter. Feb. 10, 2005. Accessed at opa.osophs.dhhs.gov/titlex/pis/opa05-01.pdf.
- Achievements in public health, 1990-1999: Family planning. MMWR 1999; 48:1,073-1,080.
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