Depo-Provera and bone density: What should you tell teen users?

For most users, benefits outweigh risks, but there are no data on teens

While family planners agree that Depo-Provera (DMPA) remains an effective form of birth control for adolescents, they continue to monitor research on the progestin-only injectable’s effect on bone density in long-term users. Why should particular attention be paid to teen DMPA users? Because it is a relatively high-dose hormonal contraceptive, DMPA suppresses ovarian estradiol production to levels found in the early to mid-follicular phase of menstruating or ovulatory women, says Andrew Kaunitz, MD, professor and assistant chair of obstetrics and gynecology at the University of Florida Health Sciences Center in Jacksonville. This lowering in serum estradiol may be of concern because estrogen maintains bone density by slowing bone resorption.1 Young women reach peak strength (density) of spinal bone about age 16, with the greatest increase in bone density occurring in the first two years post-menarche.2

Since its approval by the U.S. Food and Drug Administration in 1992, Depo-Provera has been increasingly accepted by teens. This rise is tracked through Contraceptive Technology Update’s annual pill survey. In 1994, 4% of survey respondents said it was the preferred method for teens. By 1997, 17% named it as teens’ top choice. Depo-Provera is marketed in the United States by Kalamazoo, MI-based Pharmacia and Upjohn.

As family planners know, once patients find success with a contraceptive method, they are likely to stay with it. Clinicians now may be following young women into their fifth year of Depo use, Kaunitz says. Could such long-term use affect the important years for building bone strength?

"Does it mean we might consider not providing DMPA to a patient who’s otherwise an appropriate candidate?" Kaunitz theorizes. "My opinion is no. If DMPA is an appropriate contraceptive choice, bone density concerns should not prevent use. Nonetheless, clinicians need to continue to follow the literature on the subject."

Take a look at the findings

Concern over bone density was sparked with the 1991 publication of a New Zealand cross- sectional study of 30 long-term DMPA users. This retrospective study found a difference of about 7% in bone density between DMPA users ages 25 and 51 and other premenopausal users.3 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.4

Data on teen DMPA use are limited. One study, which included adolescent users of Depo-Provera, Norplant, and oral contraceptives and those using no hormonal method found that bone density declined incrementally in DMPA users, while increasing in other subsets.5

Two recent studies of women in Thailand examined bone density among long-term DMPA users and those with IUDs and Norplant implants; those studies found similar readings among the groups.6,7 However, they looked only at adult users. A longitudinal study sponsored by Pharmacia and Upjohn is reviewing bone density in long-term Depo-Provera users, but it, too, is confined to adult women.

Clinicians should wait to see results from the longitudinal study before drawing any conclusions on DMPA’s impact on bone density, says Carolyn Westhoff, MD, MSc, associate professor in the department of obstetrics and gynecology and School of Public Health – Epidemiology at Columbia University in New York City and author of a literature review on DMPA metabolic parameters.8

"Bone is extremely plastic, and bone density goes up and down all the time in response to various situations," Westhoff notes. "Therefore, we should not jump to conclusions from the cross-sectional studies that are looking at bone density alone at just a moment in time. There is still a lot missing, even from the cross-sectional analyses, and we just have to wait to learn more."

Pending more and better data, are there any biologically similar conditions that could give clinicians insight on the long-term impact of DMPA on bone density?

Take a look at lactation, Kaunitz says. It is a condition that causes relative hypoestrogenism and is known to be associated with declines in bone density. Studies have shown that after the baby is weaned, though, bone density goes back toward baseline.

"In my mind, this is a possible biologic model for the impact of DMPA on bone density," Kaunitz says. "If that is true, it is reassuring because lactation is not, whether for one or multiple babies, recognized as a risk factor for postmenopausal osteoporosis. The issue really is not incremental declines or fluxes in bone density. What is relevant is the risk of fractures later in life, particularly in menopause."

Calcium, estrogen for Depo users?

Given the potential concern of bone density loss, should clinicians recommend calcium supplements for adolescent DMPA users? Yes, and they should endorse its use for other young women as well, says Anita Nelson, MD, medical director of the Women’s Health Care Clinic at the Harbor-University of California at Los Angeles Medical Center in Torrance. Very few teen-agers are taking in adequate calcium in their daily diets, she observes, with most drinking diet caffeinated beverages and avoiding "fattening" milk.

"In general, young women should learn about good nutrition, including adequate calcium intake," agrees Westhoff. "They also should learn about the benefits of regular exercise, which will protect their hearts, breasts, and bones."

What about providing estrogen supplementation for the long-term (five years or more) DMPA user? If this is a consideration, Kaunitz suggests the same dose level given to those DMPA users who are bothered by persistent bleeding or spotting. This approach would include oral estrogen at 1.25 mcg or a .1 transdermal patch, assuming that estrogen is not contraindicated for other reasons.

Before you add supplementation, keep in mind why the patient is on DMPA, Kaunitz cautions. If she is using the progestin-only method because she should not take estrogen, look carefully at the supplementation dosage and delivery method.

Clinicians will continue to hear about bone density and DMPA as access to bone density monitoring improves, Kaunitz says. Also, possible introduction of Cyclo-Provera may be an option in injectable contraceptives. (Cyclo-Provera may gain FDA approval in 1998. See story, at right.)

References

1. Benson RC, Pernoll ML. Benson and Pernoll’s Handbook of Obstetrics and Gynecology. Ninth ed. New York: McGraw-Hill; 1994.

2. Technical Guidance/Competence Working Group and World Health Organization/Family Planning and Popula-tion Unit. Family planning methods: New guidance. Population Reports Series J, No. 44. Baltimore: Johns Hopkins School of Public Health, Population Information Program; October 1996, p. 10.

3. Cundy T, Evans M, Roberts H, et al. Bone density in women receiving depot medroxyprogesterone acetate for contraception. BMJ 1991; 303:13-16.

4. Cundy T, Cornish J, Evans MC, et al. Recovery of bone density in women who stop using medroxyprogesterone acetate. BMJ 1994; 308:247-248.

5. Cromer BA, Blair JM, Mahan JD, et al. A prospective comparison of bone density in adolescent girls receiving depot medroxyprogesterone acetate (Depo-Provera), levonorgestrel (Norplant), or oral contraceptives. J Pediatr 1996; 129:671-676.

6. Taneepanichskul S, Intaraprasert S, Theppisai U, et al. Bone mineral density in long-term depot medroxyprogesterone acetate acceptors. Contraception 1997; 56:1-3.

7. Taneepanichskul S, Intaraprasert S, Theppisai U, et al. Bone mineral density during long-term treatment with Nor-plant implants and depot medroxyprogesterone acetate. A cross-sectional study of Thai women. Contraception 1997; 56:153-155.

8. Westhoff C. Depot medroxyprogesterone acetate contraception. Metabolic parameters and mood changes. J Reprod Med 1996; 41(5 Supplement):401-406.