Latest research sheds new light on DMPA’s impact on bone health 

Use linked to drop in density — loss may be reversed once shots stopped 

Your next patient is a 17-year-old who admits she has a hard time remembering to take the Pill, but says she wants to avoid unintended pregnancy. When you begin to counsel on the injectable contraceptive Depo Provera [depot medroxyprogesterone acetate (DMPA), Pfizer, New York City], what do you tell her about the drug?

Results from a new study indicate that women who use DMPA experience bone loss. Women in the study who used the injectable for two years recorded an approximate 6% decline in bone mineral density, compared with a loss of 2.6% among women on oral contraceptives.1 While earlier research suggests that such loss is reversible after the method is stopped, providers may want to include recommendations on calcium replacement and exercise to promote bone health.

DMPA works as a contraceptive by inhibiting pituitary gonadotropin secretion, which suppresses ovulation and ovarian estrogen production.

Concern about the impact of reduced serum estrogen on bone has prompted a number of studies of bone mineral density (BMD).

"It is clear that use of DMPA reduces ovarian production of estrogen, resulting in lowered bone mineral density," observes Andrew Kaunitz, MD, professor and assistant chair in the obstetrics and gynecology department at the University of Florida Health Science Center/Jacksonville. "What is by no means clear is whether use of DMPA causes any long-term impact on BMD or fracture risk."

Look at the research 

The new study looked at 191 women, ages 18-33, who self-selected oral contraceptives (OCs), DMPA, or nonhormonal contraception. Those selecting OCs were randomized to pills containing 35 mcg ethinyl estradiol and norethindrone or 30 mcg ethinyl estradiol and desogestrel. Researchers performed dual-energy X-ray absorptiometry to check the lumbar spine at baseline, 12 months, and 24 months.

An analysis of data indicated that bone mineral density changes among DMPA users differed significantly from those experienced by either of the pill groups or the nonhormonal contraceptive users, who were the control group.

The study’s lead author, Abbey Berenson, MD, professor of obstetrics and gynecology at the University of Texas Medical Branch, Galveston, says her research group already has started another large study on the effects of DMPA.

"We are currently conducting a prospective, controlled, longitudinal study comparing the effects of DMPA and 20 mcg pills on bone mineral density," she states. "We will recruit more than 700 women between 16 and 33 years of age from three racial/ethnic groups to participate in this study; furthermore, we will measure biomarkers and examine the issue of reversibility."

How about teens? 

What is the evidence when it comes to teen use of DMPA? Bone health is a special concern when it comes to adolescents: Half of a woman’s bone mass is gained during puberty and the first several years after menarche. Peak bone mass is achieved in the early to mid-20s.2

Since the Food and Drug Administration approved Depo-Provera in 1992, use of the drug has grown among adolescent users. While about half of teens report Pill use and a third say they use condoms, about 10% record use of DMPA.3

Researchers at the Seattle-based Group Health Cooperative’s Center for Health Studies have been examining use of DMPA in women and teens. In one study, researchers found that women who used DMPA continuously for three years experienced about the same amount of bone loss as women who are breast-feeding or going through menopause; however, women steadily regained bone density once they stopped using the contraceptive.4 The Seattle scientists now have evaluated bone density changes with DMPA use and discontinuation in a cohort of adolescents, says Delia Scholes, PhD, senior investigator at the Center. Information on the study was presented at the September 2003 meeting of the Washington, DC-based American Society for Bone and Mineral Research.5

"In this latest study, use of DMPA contraception in adolescents was associated with significant continuous losses of bone density at the hip and spine," says Scholes. "However, once again, we saw significant gains post-discontinuation, and so we have further evidence that the loss of bone mass is largely reversible."

What is your approach? 

How should clinicians interpret current evidence regarding use of DMPA, particularly in adolescents?

Berenson contends that the new research should be used on a limited basis to help determine the best method of contraception for the patient. If the patient can take oral contraceptives reliably, has no contraindications to estrogen, and agrees to their use, oral contraceptives may represent a better choice than DMPA for the adolescent patient, she says.

"However, if the patient cannot use pills or the contraceptive patch correctly, or if she has a contraindication to estrogen, DMPA should still be considered as an option as it is a very effective method for avoiding unintended pregnancy," states Berenson.

Kaunitz contends that currently available data suggest use of DMPA by reproductive-age women does not cause BMD deficits years or decades later.6,7

"As we await more data regarding long-term impact of DMPA use on skeletal health in teens, it makes sense to recommend the same bone healthy advice to DMPA users as to other young women: achieve adequate calcium intake, exercise regularly, and don’t smoke," he states.

Encourage women to get more calcium into their diet through such food items as fortified juice and chewable candies. Also suggest use of calcium supplementation, advises David Archer, MD, professor of obstetrics and gynecology and director of the Clinical Research Center at the Eastern Virginia Medical Center in Norfolk.

"Most women do not take in sufficient calcium in their diet," comments Archer. "It is important to note that low estrogen levels reduce absorption of dietary calcium."

References 

1. Berenson AB, Breitkopf CR, Grady JJ, et al. Effects of hormonal contraception on bone mineral density after 24 months of use. Obstet Gynecol 2004; 103(5 Pt 1):899-906.

2. DMPA and bone density loss: An update. Contraception Report 1999; 10: Accessed at: www.contraceptiononline.org/contrareport/article01.cfm?art=86.

3. Abma JC, Chandra A, Mosher WD, et al. Fertility, family planning, and women’s health. New data from the 1995 National Survey of Family Growth. Vital Health Stat 1997; Series 23.

4. Scholes D, LaCroix AZ, Ichikawa LE, et al. Injectable hormone contraception and bone density: Results from a prospective study. Epidemiology 2002; 13:581-587.

5. Scholes D, LaCroix AZ, Ichikawa LE, et al. Effects of use and discontinuation of depot medroxyprogesterone acetate injectable contraception on bone density in adolescents: Results from a longitudinal study. Presented at the 25th Annual Meeting of the American Society for Bone and Mineral Research. Minneapolis; September 2003.

6. 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.

7. Petitti DB, Piaggio G, Mehta S, et al. Steroid hormone contraception and bone mineral density: A cross-sectional study in an international population. The WHO Study of Hormonal Contraception and Bone Health. Obstet Gynecol 2000; 95:736-744.