CONTRACEPTION
Subcutaneous depot medroxyprogesterone acetate for birth control and endometriosis pain.
Uncertain value for adolescents
DMPA should be carefully considered for use in adolescent girls—and this proviso includes the subcutaneous formulation.
Adolescence is a critical period for bone mineralization. Thus, any agent that limits bone accretion should be prescribed only after weighing all the other options.
A prospective cohort study in adolescents found a 3.1% decrease in BMD after 2 years of DMPA use, versus a 9.5% increase among nonusers.11 More recent reports indicate significant gains in BMD and reversal in bone loss once the drug is discontinued.12
What the “black box” warning means
Based in part on results from these studies, the Food and Drug Administration (FDA) and the drug’s manufacturer issued a black box warning for both the IM and subcutaneous formulations of DMPA. This step was taken to highlight the fact that users of DMPA may lose significant BMD, and that this loss may increase with duration of use and may not be entirely reversible.
The warning recommends that the drugs be used as long-term birth control only if other methods are inadequate. It emphasizes the general lack of certainty about the effect of these drugs on peak bone mass (when used in adolescence or early adulthood) and the risk of osteoporotic fracture (later in life).
How to counsel patients
I discuss the black box warning with each patient in the larger context of contraceptive counseling. The lower efficacy and other problems associated with daily birth control methods must be weighed against the risk of bone loss in both adolescents and adults.
It also is important to consider other risk factors for osteoporosis, such as chronic alcohol or tobacco use, eating disorders, or chronic use of corticosteroids. Adolescents who have poor eating habits or who use alcohol or tobacco may be at heightened risk of BMD loss.
Once a woman chooses DMPA, she should be encouraged to maintain a healthy lifestyle, including adequate calcium intake, weight-bearing and musclestrengthening exercises, smoking cessation, and moderate to no alcohol intake.
BMD measurements are not recommended since they do not predict fracture risk in premenopausal women.
Other side effects
Though rare, serious thrombotic events have been reported in women using the IM formulation.
Also rare are ocular disorders (loss of vision, proptosis, diplopia, or migraine) and ectopic pregnancy.
Other possible side effects include injection site reactions, decreased libido, acne, headache, fatigue, gastrointestinal disorders (distention, abdominal pain, diarrhea, nausea), infection, arthralgia, back pain, limb pain, dizziness, insomnia, anxiety, depression, breast pain and/or tenderness, and hot flushes.
Return to ovulation
DMPA is associated with a prolonged return to ovulation once it is discontinued. In a large US study of women who discontinued intramuscular DMPA to become pregnant, 68% conceived within 12 months, 83% conceived within 15 months, and 93% conceived within 18 months of the last injection, with a median time to conception of 10 months.13
Though no studies have determined the median time to conception for subcutaneous DMPA, it is likely to be similar to the 10-month interval seen with the IM formulation.
Comparing drugs head to head
The IM and subcutaneous formulations were compared prospectively at a single US center.14 The study defined return to ovulation as the first time serum progesterone levels reached at least 4.7 ng/mL. At the end of 12 months (postinjection), the cumulative rate of ovulation was 97.4% for subcutaneous DMPA and 94.7% for the IM formulation.
Ovulation occurred at a median of approximately 7 months (subcutaneous route) and 6 months (IM).
Early ovulation is possible
One subject in the subcutaneous DMPA group ovulated 14 weeks after her last injection. Thus, it is important to adhere to the recommended dosing schedule of 12 to 14 weeks.
Weight gain: 0 to 7.5 lb
Reports of weight gain with DMPA have been highly variable. Many women who discontinue hormonal contraceptives cite weight gain as the reason. With one third of US women meeting the criteria for obesity—a number that is likely to rise—and with ethnic variations, it is difficult to determine the exact impact of DMPA.
A well-designed, placebo-controlled trial by Pelkman and colleagues15 found DMPA to have no effect on resting energy expenditure, food intake, or body weight. Three large clinical trials of subcutaneous DMPA found a mean weight gain of 3.5 lb during the first year of use, and a small 2-year study comparing IM and subcutaneous DMPA found mean weight gains of 7.6 and 7.5 lb, respectively.
Combating endometriosis pain
With the FDA’s approval of subcutaneous DMPA for treatment of endometriosis-associated pain, the drug expands the pharmacologic choices for endometriosis pain relief for the first time in 15 years, with less frequent side effects than the other widely used drug, leuprolide acetate.
