DMPA’s effect on bone mineral density: A particular concern for adolescents

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Applied Evidence

DMPA’s effect on bone mineral density: A particular concern for adolescents

J Fam Pract. 2009 May;58(5):E1-E8

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References

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TABLE 2
DMPA’s effect on BMD in adolescent women: What the studies reveal

AUTHOR (TYPE OF STUDY)	# OF PARTICIPANTS/ POPULATION DESCRIPTION	OUTCOME MEASURE	RESULTS	COMMENTS
Scholes, 2004³² (cross-sectional)	n=81 (DMPA) n=93 (comparison) Ages 14-18 Current users of DMPA, range of 1-13 injections (mean 3)	DEXA proximal femur and LS spine	Neither total hip (P=.1) nor spine (P=.19) BMD was significantly lower in DMPA users	17 non-DMPA users were taking OCPs DMPA users were more likely to be African American and to have a previous pregnancy
Beksinska, 2007³³ (cohort)	n=115 (DMPA) n=144 (comparison) Ages 15-19 New users of DMPA Comparison group not using hormonal contraception	DEXA of distal radius and ulna	No significant difference in BMD between groups (P=.88)	51 DMPA users completed the study vs 91 nonusers of hormonal contraception Majority of cohort was African American
Cromer, 2004³⁴ (cohort)	n=53 (DMPA) n=152 (comparison) Ages 12-18 New users of DMPA Comparison group not using hormonal contraception	DEXA of femoral neck and LS spine Measured at baseline, 6 months, and 12 months	LS spine BMD decreased in DMPA group 1.4% and increased in control group 3.8% (P<.001); femoral neck BMD decreased in DMPA group 2.2% and increased in control group 2.3% (P<.001)	45% dropout rate by 12 months in the DMPA group
Lara-Torre, 2004³⁵ (cohort)	n=58 (DMPA) n=19 (comparison) Ages 12-21 New DMPA users Comparison group ages 15-19 not using any hormonal contraception	DEXA of LS spine Measured at baseline and every 6 months for 2 years	DMPA group had significantly more BMD changes than control group at each check: -3.02% at 6 months (P=.014); -3.38% at 12 months (P=.001); -4.81% at 18 months (P<.001); -6.81% at 24 months (P=.01)	DMPA group was more likely to be African American DMPA group had dropout rates of 54% at 12 months and 64% at 24 months
Scholes, 2005³⁶ (cohort)	n=80 (DMPA) n=90 (comparison) Ages 14-18 Baseline users of DMPA (duration of use from 1 to 13 injections)	DEXA of hip, spine, and whole body Measured at baseline and every 6 months for 24-36 months	Significant BMD decreases in DMPA users at each check vs comparison group in hip and spine (P=.001), but not in whole-body BMD (P=.78) Most discontinuers had regained BMD back to baseline by 12 months	18.9% of non-DMPA users were taking OCPs 61 participants discontinued DMPA during the study DMPA group more likely to smoke and to have been pregnant
BMD, bone mineral density; DEXA, dual-energy x-ray absorptiometry; DMPA, depot-medroxyprogesterone acetate; LS, lumbosacral; OCPs, oral contraceptive pills.

Can estrogen therapy counteract DMPA’s effect?

If decreased BMD in women taking DMPA is due to low estradiol levels, it is logical that a trial of estradiol supplementation would mitigate the negative effect. Indeed, a bone-protective effect of supplemental estrogen therapy has been found in studies of young women with amenorrhea secondary to the female athlete triad. Similarly, in postmenopausal women with low serum estradiol levels, supplemental estrogen therapy helps maintain BMD.¹⁸

FAST TRACK

Recommend calcium and vitamin D supplementation with DMPA use.

Two randomized trials have evaluated the use of supplemental estrogen on the adverse effects of DMPA on bone.^19,20 The trial by Cromer et al¹⁹ randomized 123 adolescent women ages 12 to 18 to receive either estrogen supplementation or placebo. They found that the participants in the estrogen group had BMD gains vs BMD losses among those in the placebo group over the 2-year period of the study (2.8% vs -1.8% at the LS spine, and 4.7% vs -5.1% at the femoral neck; P<.001 for both). The limitations to this study include a high dropout rate (53 participants had left by 24 months) and incomplete data collection due to early stoppage of the study.

Cundy et al²⁰ studied 38 adult women who had been on DMPA for at least 2 years and had below-average LS spine BMD. Nineteen women were randomized to receive estrogen supplementation and underwent bone density tests every 6 months; 19 women were also in the comparison placebo group. In the estrogen supplementation group, there was significant attenuation of lowering BMD that increased throughout the trial. However, only 26 subjects completed the 2-year study.

Limit DMPA use to 2 years? Experts disagree

The FDA, in 2004, placed a black box warning on DMPA: “Women who use Depo-Provera Contraceptive Injection may lose significant bone mineral density. Bone loss is greater with increasing duration of use and may not be completely reversible. It is unknown if use of Depo-Provera Contraceptive Injection during adolescence or early adulthood, a critical period of bone accretion, will reduce peak bone mass and increase the risk of osteoporotic fracture later in life. Depo-Provera Contraceptive Injection should be used as a long-term birth control method (eg, longer than 2 years) only if other birth-control methods are inadequate.”²¹ In light of these FDA guidelines, many practitioners have started limiting patients’ use of DMPA to 2 years.