Injectable Progestins and Bone Loss: Is It Reversible?

Injectable depot medroxyprogesterone acetate (DMPA) is a highly effective, long-acting injectable progestin contraceptive (IPC) that is widely used by teenagers in the U.S. However, concerns about use during adolescence, when bone density is rapidly increasing, have arisen based on studies showing that DMPA users have lower bone-mineral density than nonusers. In 2005, the FDA required a “black box” warning about risk for bone loss on DMPA labels. To assess the effects of IPCs on bone density and to determine whether bone loss is reversible, investigators assessed calcaneal (heel) bone thickness by ultrasound in 3487 premenopausal black and mixed-race women (age range, 18–44) in South Africa who provided detailed histories of contraceptive use (including age at menarche). Overall, 8% had never used an IPC, 36% had only ever used DMPA, 26% had only ever used another IPC (not available in the U.S.), and 30% had used DMPA and another IPC.

In analyses of all IPC users, bone density was lowest among current IPC users and among those with the longest duration of use (≥10 years). However, mean bone density measurements in women who had stopped IPC use 2 to 3 years earlier were similar to or greater than those in never-users. Analysis of women aged 18 to 34 (controlling for age, ethnicity, BMI, age at menarche, physical activity level, and cigarette use) showed no difference in mean bone density between women who started IPC use at or before age 15 and those who started later. Among women aged 35 to 44, measurements were comparable for women who started at or before age 17 and those who started later. No differences were observed between the two types of IPCs.