Bone Mineral Density and Depot Medroxyprogesterone Acetate Contraception

Abstract

Source: Scholes D, LaCroix AZ, Ichikawa LE, et al. Change in bone mineral density among adolescent women using and discontinuing depot medroxyprogesterone acetate contraception. Arch Pediatr Adolesc Med. 2005;159:139–144.Depot medroxyprogesterone acetate (DMPA) is used as a contraceptive method by 10% of United States women ages 15–19 years.1 The results of several studies have raised concerns about the effect of DMPA on bone mineral density (BMD) and the implications for later osteoporosis and fracture risk. Most of these previous studies have been in adult women.2–4 These authors, from Seattle, Washington, previously reported a decrease in BMD during use of DMPA in women who were 18–21 years old and a regain of BMD following discontinuation.5 The current project is a 3-year prospective study of women 14–18 years old. A total of 80 study participants used DMPA for contraception, while 90 did not. Study patients were recruited from a mixed-model managed health care system in the Pacific Northwest using a population-based sampling of computerized files of patients ages 14–18 years either receiving or not receiving DMPA injections. Thirty percent of the young women in the project were 14–16 years old, and 30% were nonwhite. At baseline, 30% of the DMPA users had received 1 injection, 31% 2–3 injections, 21% 4–7 injections, and 18% 8–13 injections. DMPA-exposed patients were more likely to be cigarette smokers, to have been pregnant, to have had an earlier age of menarche, to have lower calcium intake, to have higher body mass index and body fat, and to wear navel jewelry. Dual energy x-ray absorptiometry was used to measure BMD of the hip, spine, and total body in all 170 study patients at baseline; follow-up scans were completed on 90% of patients at 6 months after enrollment, 84% at 12 months, 82% at 18 months, and 78% at 24 months. During the study, 71% of DMPA users discontinued use and were followed up to 36 months. The primary study outcome was BMD change, and this was compared in continuous DMPA users, those who discontinued using it, and nonusers. Linear regression analysis was used to assess adjusted mean percentage change from baseline at 6, 18, and 24 months.At baseline, there were no significant differences in BMD between patients in the 3 groups. For those continuing DMPA use, mean BMD declined at the hip and spine but whole body BMD increased slightly. The effect was greater for new users (1 shot) than for prevalent users. The adjusted mean change in BMD for each 6-month interval decreased with increasing use but loss continued past 24 months. Changes between users and nonusers were highly significant. After discontinuation, BMD increased, and by 18 months the adjusted mean change from baseline was significantly higher for discontinuers than for nonusers. After 12 months, the adjusted mean BMD values were the same in discontinuers and comparison subjects.The authors conclude that teenage women using DMPA have continuous and significant decline in adjusted BMD at the hip and the spine, with changes greatest in the first 1–2 years of use. The decrease of about 5% in BMD could have clinical consequences if the changes were not reversed. However, they also conclude that following discontinuation of DMPA, there is rapid recovery of BMD, especially at the spine and whole body. These changes are similar to the transient effects of lactation on BMD.6Dr. Brookman has disclosed no financial relationships relevant to this commentary.DMPA has been used as an effective method of pregnancy prevention for more than 30 years, especially outside the US. It was approved for general use as a contraceptive by the FDA in 1992. Because it is a long-acting method, requiring adherence only to an injection every 12 weeks, it is often favored by parents and health care providers for use in young adolescents. Concerns have been raised about the effects of DMPA on BMD, especially at an age when there is peak deposition of calcium in bones. One group studied 58 new users of DMPA who were 12–21 years old, 71 users of oral contraceptives 11–19 years old, and 19 normal menstruating 15- to 18-year-old women. They measured BMD every 6 months for 2 years, noting a statistically significant decrease in BMD in DMPA users compared with controls, and a difference between DMPA and oral contraceptive users which was significant only at 12 and 18 months.7 Another group studied 29 DMPA users, 79 oral contraceptive users, and 107 controls, all ages 12–18 years at baseline, with follow-up at 6 and 12 months. They also found a loss of BMD in DMPA users compared to an increase in BMD in the other 2 groups.8 Both studies used the same methodology summarized above, both observed losses in BMD of 2–5% with continuing loss over time, and both hedge on the clinical importance of the BMD changes relative to the prevention of pregnancy in young adolescents.The current authors provide reassurance that DMPA-associated changes in BMD may not be clinically significant and likely are reversible. However, only one-third of these subjects were less than 17 years old and none were less than 14 years of age. Bone mineralization peaks around the time of menarche, which occurs in most girls between ages 11 and 14. Until there are additional studies following DMPA users for many years, there is a need to consider the possible risks for future bone health when deciding to use DMPA for pregnancy prevention, especially in young adolescents. Clinicians should counsel young DMPA users about adequate calcium intake, consider studying bone density after some interval of use, such as 1 or 2 years, and consider adding estrogen for those who show a loss of BMD.