Are There Contraindications to Switching From Intramuscular to Subcutaneous Depo-Provera?

Laurie E. Scudder, MS, NP-C


December 16, 2008

I have several adolescent female patients who are receiving intramuscular Depo-Provera® and doing well. What should I consider before switching them to the new subcutaneous preparation? Are concerns about decreasing bone mineral density the same for both products?

Response from Laurie E. Scudder, MS, NP-C
Adjunct Assistant Professor, School of Health Sciences, George Washington University, Washington, DC; Curriculum Coordinator, Nurse Practitioner Alternatives, Inc., Ellicott City, Maryland; Nurse Practitioner, Baltimore City School-Based Health Centers, Baltimore, Maryland

Depot medroxyprogesterone acetate (Depo-Provera®, DMPA) is a very good option for contraception in adolescents. Numerous studies have documented the overall effectiveness and acceptability of this method for teens. In fact, a recent study found that postpartum teens using DMPA were significantly less likely to become pregnant than teens using oral or patch contraceptives.[1]

DMPA suppresses the hypothalamic-pituitary-ovarian axis, resulting in a hypoestrogenic state and a decline in bone metabolism.[2] Concerns about decreasing bone mineral density (BMD) led to the issuance of a Food and Drug Administration (FDA) black box warning in 2005. This warning stated that women should be informed of the risk for reduced BMD and that use of the product should be limited to 2 years unless other options are unadvised.[3] To date, there is no evidence that decreased BMD confers an increased risk for fractures. Furthermore, the lowered BMD appears to be largely, although perhaps not completely, reversible upon discontinuation of the product. Nevertheless, concerns about the potential for reduced BMD have resulted in lower rates of prescribing DMPA.[4]

Although there are some unanswered questions about this adverse effect in adolescents, the bulk of evidence to date suggests that these concerns are outweighed by the advantages of this contraceptive method in this age group, particularly in young girls who have not been successful with other methods. The World Health Organization,[5] the Society of Obstetricians & Gynecologists of Canada,[6] and the Society for Adolescent Medicine[2] are unanimous in their recommendation that DMPA can be safely used, provided there is appropriate patient education on calcium and vitamin D supplementation, encouragement of weight-bearing exercise, smoking cessation, and decreased alcohol and caffeine intake.

Until recently, DMPA was available only as a 150-mg/mL intramuscular preparation. However, in 2005, a 104-mg/mL subcutaneous preparation was approved by the FDA (Depo-subQ Provera 104™; Pfizer) (DMPA-subQ).[7] This newer preparation is equally effective, despite an almost 30% reduction in the dose, and is not affected by weight or race.[8] In fact, no pregnancies occurred during the open-label trials involving over 16,000 cycles.[9] There appear to be no significant differences in BMD losses between women using the intramuscular and subcutaneous preparations.[10]

Little literature addresses considerations important in switching patients from intramuscular to subcutaneous preparations available. However, clinicians should consider several issues:

  1. Cost -- The new subcutaneous preparation is more expensive, although prices vary. Not all health plans include DMPA-subQ in their formularies.

  2. Adverse effect profile -- Both preparations are associated with breakthrough bleeding, although the patterns are somewhat different. With both preparations, breakthrough bleeding and spotting resolve for most women within 3 to 4 cycles. Other adverse effects, including acne, libido changes, injection site reactions, and headache, are similar with the 2 preparations.

  3. Weight gain -- The package insert for DMPA-subQ notes that mean weight gain for the 2 preparations is similar. However, anecdotally, many clinicians, as well as the Managing ContraceptionWebsite,[11] report that the subcutaneous preparation is associated with less weight gain than the intramuscular preparation, typically about one third less in the first year of use.

  4. Efficacy -- Although both products are very effective, the clinical trials of DMPA-subQ were conducted using a 14-week dosing interval, 1 week longer than for the intramuscular preparation. While the recommended dosing interval for both products is the same (12-14 weeks), the subcutaneous preparation may provide a somewhat longer window of effective contraception in young women who present late for a dose.

  5. Privacy and convenience -- The subcutaneous product, although not approved for self-administration, has been tested as a self-administered preparation and is probably used off-label in that fashion.

In summary, the subcutaneous preparation is as effective as the intramuscular preparation, and adverse effect profiles, including BMD loss, are similar. There should be no problem in switching adolescent patients from the intramuscular to the subcutaneous preparation of DMPA.


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