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Recent research on the effect of the contraceptive injectable depot medroxyprogesterone acetate (DMPA, Depo-Provera, Pharmacia Corp., Peapack, NJ) on bone mineral density (BMD) offers reassurance regarding long-term use of the drug.
Questions about DMPA’s impact on BMD arose with the publication of a New Zealand cross-sectional study of 30 long-term DMPA users.1 This retrospective study found a difference of about 7% in bone density between DMPA users ages 25 and 51 and other premenopausal users. A subsequent study of some of the original DMPA users who discontinued the method found that bone density tended to increase after the method was stopped.2 (Discussion of these studies and others examining DMPA’s impact on BMD can be found in Contraceptive Technology Update, January 1998, p. 1.)
Results from a just-published longitudinal cohort study of 59 Chinese women have led its researchers to conclude DMPA can be used on a long-term basis without fear of linear bone loss leading to early osteopenia and osteoporosis.3
Two recent cross-sectional studies,4,5 which indicate DMPA’s effect on BMD is small and reversible, offer reassurance to women who choose the injectable contraceptive, says Andrew Kaunitz, MD, professor and assistant chair in the obstetrics and gynecology department at the University of Florida Health Science Center in Jacksonville.
"In my opinion, concerns regarding BMD should not discourage otherwise appropriate candidates or their clinicians from using this convenient, highly effective contraceptive," states Kaunitz.
Assess the impact
DMPA is the third most popular form of birth control among Hong Kong women, says Grace Tang, MD, professor at the University of Hong Kong, and a co-author of the study. In order to get a broader view of the drug’s impact on BMD, the Chinese research group did a cross-sectional study on DMPA users (ranging from five to 15 years in use) and published the results in 1999.6
"We made an estimate of the likely rate of bone loss," Tang observes of the 1999 research. "We then proceeded to verify the results in a longitudinal follow-up of this cohort to see if our projection was correct."
The longitudinal cohort study revealed the study subjects’ annual rate of bone loss at three sites was substantially less than the projected values in the cross-sectional study, which had demonstrated a reduction in BMD in DMPA users.
"We have plans to do a prospective study from point zero," reports Tang. "The concern is the recruitment time needed to get adequate number of subjects; in our study, the subject number was only 67."
Why have questions continued on DMPA’s impact on bone health?
"In my opinion, the variable results may be related to 1) sample demographic differences; 2) lack of baseline values of BMD, meaning that subjects may start with very different BMD levels in different populations; and 3) varying periods of time in making the observations in BMD in different studies, and the BMD loss may not be linear in nature," observes Tang.
The benefits of DMPA continue to outweigh the concerns about BMD, says Kaunitz. He points to the results of the Orr-Walker and Petitti cross-sectional studies, which assessed women who were former users of DMPA. Both found that long-term after DMPA use, BMD in former users is similar to that of never-users.
"This is strikingly similar to picture with BMD and lactation, since BMD declines during lactation, then goes back to normal after baby is weaned," notes Kaunitz. "Taken together, these studies suggest that the BMD declines seen in current DMPA users may be transient, and without long-term clinical significance."
1. Cundy T, Evans M, Roberts H, et al. Bone density in women receiving depot medroxyprogesterone acetate for contraception. BMJ 1991; 303:13-16.
2. Cundy T, Cornish J, Evans MC, et al. Recovery of bone density in women who stop using medroxyprogesterone acetate. BMJ 1994; 308:247-248.
3. Tang OS, Tang G, Yip PS, et al. Further evaluation on long-term depot-medroxyprogesterone acetate use and bone mineral density: A longitudinal cohort study. Contraception 2000; 62:161-164.
4. Orr-Walker BJ, Evans MC, Ames RW, et al. The effect of past use of the injectable contraceptive depot medroxyprogesterone acetate on bone mineral density in normal post-menopausal women. Clin Endocrinol (Oxf) 1998; 49:615-618.
5. Petitti DB, Piaggio G, Mehta S, et al. Steroid hormone contraception and bone mineral density: A cross-sectional study in an international population. Obstet Gynecol 2000; 95:736-744.
6. Tang OS, Tang G, Yip P, et al. Long-term depot medroxyprogesterone acetate and bone mineral density. Contraception 1999; 59:25-29.