Should adolescent girls be given depot medroxyprogesterone acetate?

September 1, 2006

In light of the FDA's black box warning about potential bone loss in teenagers, how do you counsel teenagers about this highly effective birth control method? Recommendations from the World Health Organization provide a practical, evidence-based approach to weighing the risks.

DR. EDELMAN is assistant professor, department of obstetrics and gynecology, Oregon Health and Science University, Portland, Ore. She hasnothing to disclose in regard to affiliations with, or financial interests in, any organization that may have an interest in any part of thisarticle, which is adapted from Contemporary OB/GYN, an Advanstar publication.

DR. JENSEN is professor, department of obstetrics and gynecology, Oregon Health and Science University, Portland, Ore. Dr. Jensen reportsthat he receives grant/research support from and is a retained consultant for Wyeth-Ayerst and Berlex (and is also on the latter’s speaker’sbureau); he also receives grant/research support from Organon, Symbollon, Pfizer (which makes DepoProvera), and Warner-Chilcott.

If you feel uneasy prescribing depot medroxyprogesterone acetate (DMPA [Depo-Provera Contraceptive Injection]) to adolescent patients in light of the Food and Drug Administration's (FDA) recent black box warning, and find yourself grappling uncomfortably with this option when advising and treating teenagers who need contraception, you're not alone.

Unfortunately, the FDA's recent black box warning about the adverse effects of DMPA on bone density in adolescents has left many clinicians at a loss for how to advise and treat their teenage patients. Some have stopped providing DMPA to adolescents, while others continue to prescribe it, but feel uneasy doing so. With the United States leading other developed countries in the teenage pregnancy rate, clinicians need to carefully weigh concerns about the effects of DMPA on bone density against the consequences of withholding this important contraceptive option.3 The alternative, an unplanned pregnancy, could severely harm-even ruin-an adolescent's future. To help interpret this information, let's examine the evidence behind the FDA's decision.

How does DMPA work, and why does it affect bone density?

DMPA works by inhibiting the pituitary gland from secreting gonadotropin, especially luteinizing hormone (LH). It provides contraception by blocking the LH surge and thereby prevents ovulation.4 Additional mechanisms of contraception include a progestin-induced thickening of the cervical mucus (preventing sperm from penetrating) and thinning of the endometrial lining (creating an inhospitable environment for ovum and sperm).

Estrogen suppresses bone remodeling and resorption, and lower levels or a lack of estrogen (as occurs in menopause) can negatively impact bone density.4 Although DMPA suppresses follicle-stimulating hormone (FSH), this effect is typically not complete, and most users' ovaries continue to produce some estradiol.4 Because many of these young women experience symptoms of hypoestrogenism, however, we must consider the effect on bone density. An additional concern for teenagers is that peak bone mass in females occurs in late adolescence.5 Theoretically, lower levels of estrogen during DMPA use in the active phase of bone development might affect the skeleton more than with use later in life. The reassuring news is that the recovery of bone density after DMPA use in teenagers appears to be no different than that of breastfeeding.6,7 In addition, bone mineral density (BMD) is only a surrogate for fracture risk, and no information exists on how this temporary decrease in BMD during DMPA use might translate to future fracture risk.

What does the literature show?

Studies of adolescents show this same association between BMD loss and DMPA (Table 1). Like adults, the decrease in BMD among DMPA users compared to non-users is small and is less than one standard deviation after two years of use.20 To date, there are no studies that show how this small temporary decrease in BMD increases the risk of osteoporosis or fracture risk.