Depo- medroxy progesterone acetate (DMPA; Depo-Provera®) is a deep intramuscular injection of 150 mg of medroxyprogesterone acetate (MPA) every 12 weeks. Pharmacologically active levels (>0.5mg/ml) of MPA are achieved within 24 hours of injection. Serum levels remain >1.0ng/ml for approximately three months after administration. By the fifth month, levels drop to 0.2mg/ml (92). DMPA's main mechanism of action is inhibition of ovulation.

Non contraceptive benefits of DMPA (93).

Decreased risk of:

Improvements of the following conditions:

Efficacy: With typical use, the failure rate is 0.3 per 100 woman-years which is similar to rates found with surgical sterilization (94). Variations in body weight and concurrent medications have not been shown to alter efficacy (95).

Side Effects: The most commonly cited side effects of DMPA are changes in menstrual patterns, weight, and mood. After 3 months of use, almost one-half of DMPA users report amenorrhea with the majority of the remaining women complaining of irregular bleeding (96). By the end of one year, nearly 75% of users will experience amenorrhea (97). Short courses of high dose estrogen do little to reduce bleeding among DMPA users (98). In addition, early readministration of DMPA (at 8-10 weeks instead of 12 weeks) does not reduce bleeding (99). Although many users of DMPA report weight gain, recent controlled studies show that its long-term use does not cause a significant increase in body weight (100). Product labeling for DMPA includes depression as a possible side effect. Two well-designed studies addressed the issue of depression and DMPA use. Patients followed up to one year after DMPA initiation showed no worsening of depressive symptoms compared to those who did not use Depo-Provera (101,102). Clinical trial setting, DMPA does not cause statistically significant weight gain (103-105). However, African American women and Navahos and women with high baseline body mass index may be predisposed to weight gain with the use of this method (104). New studies have shown that neither DMPA nor progestin only injectable is associated with increased risk of breast cancer.

Risks: A recent review showed that levels of triglyceride and total cholesterol do not change with DMPA use (106). Seven of the ten studies that measured serum lipid levels revealed a decrease in high density lipoprotein (HDL) while three out of five studies showed an increase in mean low density lipoprotein (LDL) levels. The clinical significance of these findings remains to be determined. In contrast to combination OCs, Depo-Provera is not associated with increases in coagulation-related factors or in blood pressure (107). A small but nonsignificant increase in the risk of VTE is noted in users of progestin-only injectable contraception (91). Recent studies provide reassuring evidence that decreases in bone mineral density in current and recent Depo-Provera users are reversible and appear to be similar to changes seen in lactation (108).

Bone loss: On November 17, 2004, the FDA placed a black box in DMPA package labeling regarding the long-term use of DMPA and bone loss. Anecdotally, this warning had an immediate impact on decreased prescription of DMPA. Depot medroxyprogesterone acetate use has not been linked to menopausal osteoporosis or fractures. A Cross-sectional study from the WHO demonstrated that in that years after use, BMD in former adult DMPA users is similar to that of never users (109) The 2002 cohort study of BMD in adult women performed by Scholes et al. (110), a National Institutes of Health-funded investigator in Seattle, demonstrated that at 3 years of follow-up, BMD of former DMPA users was comparable to that of never users of injectable contraception. While the FDA warning also specifically heightened concerns about teens and bone loss in the setting of DMPA, a 2005 report from Scholes et al. (111) showed that use of DMPA in this population does not put patients at risk for osteoporosis later in life. This cohort study followed 170 adolescents (including 80 who used DMPA at baseline) and found that recovery of BMD was complete within 12 months following DMPA discontinuation. BMD was ultimately observed to be higher in the former than in the never users of DMPA. Duration of DMPA use was not observed to impact speed of BMD recovery following DMPA discontinuation.