DMPA suppresses ovarian estrogen production. Prospective studies demonstrated bone loss during DMPA therapy, with recovery of bone mass after DMPA use is discontinued (229). Similar bone loss and then recovery occurs with lactation. Adolescents are of special concern because they normally gain bone mass; most of adult bone mass is attained by age 20. Estrogen injections prevent the bone loss and allow adolescent women to gain bone density despite use of DMPA (230). A long-term study in adolescents documented bone density loss and confirmed recovery of lumbosacral bone mineral density to baseline by 60 weeks after discontinuation of DMPA and significant gain above baseline by 180 weeks. Recovery of density at the hip was slower, 240 weeks to significant gain (231). A systematic review of DMPA clinical trials could find no studies where fracture was an outcome, so whether long-term use leads to fractures is still not known (232). The FDA black box warning added to DMPA labeling proposes that DMPA treatment be limited to 2 years at a time, unless the patient has no other good options for contraception. For many women, especially in third world countries, DMPA is often the only option for highly effective contraception because it is inexpensive and easy to administer. The issue should be discussed with women who are considering DMPA, but DMPA should not be routinely discontinued after 2 years unless the patient wants to conceive or wants to change to another contraceptive method for other reasons.
The effect of DMPA on plasma lipids is inconsistent; DMPA users appear to have reduced total cholesterol and triglyceride levels, slight reduction in HDL cholesterol, and no change or slight increase in LDL cholesterol, all of which are consistent with a reduction in circulating estrogen levels. In some studies, the decrease in HDL and increase in LDL are statistically significant, although the values remain within normal ranges (233). DMPA is not associated with myocardial infarction. Glucose tolerance tests disclose a small elevation of glucose in DMPA users.
There is no change in hemostatic parameters, with the exception that antithrombin III levels are sometimes reduced with chronic therapy (233). Venous thrombosis and thromboembolism have occurred in women on DMPA, but this is very rare (234). As noted earlier, large epidemiologic studies have not found DMPA to be associated with thrombosis (130). Thrombotic episodes occurred in elderly women with advanced cancer who were treated with a variety of agents, including DMPA and tamoxifen (235). Another episode occurred in a woman with a cerebral metastasis from breast cancer (236). Such patients are at high risk for thrombosis regardless of the use of DMPA. Two cases of retinal vein thrombosis were reported. Both women were hypertensive and one of them smoked cigarettes (237).
DMPA is not associated with teratogenesis (238). Nor is it associated with affective disorders or mood changes (239).