- Discuss the potential for decreased bone mineral density in using depot-medroxyprogesterone acetate (DMPA) with any woman who is thinking of it as a means of contraception (C).
- Recommend to women that they take 1300 mg of calcium and 400 IU of vitamin D when using DMPA (C).
- Consider prescribing estrogen replacement if DMPA is going to be used for more than 2 years (C).
Strength of recommendation (SOR)
- Good-quality patient-oriented evidence
- Inconsistent or limited-quality patient-oriented evidence
- Consensus, usual practice, opinion, disease-oriented evidence, case series
Among adolescent women who use contraception, the injectable progestin-only depot-medroxyprogesterone acetate (DMPA, Depo-Provera) is second in popularity only to oral contraceptive pills.1 A very real drawback with DMPA, however, is a resultant hypoestrogenic state that has been linked to lowered bone mineral density (BMD).
Although several studies have demonstrated a relationship between DMPA use and lower BMD among adults and adolescents (strength of recommendation [SOR]: B), many of them had small sample sizes and methodological flaws. Moreover, most studies have shown that BMD change is reversible after discontinuation of DMPA.
Experts recommend counseling young women about DMPA’s possible effects on bone. But they caution against limiting its use based on the insufficient research to date (SOR: C). Analysts estimate that the availability of DMPA has contributed significantly to decreased adolescent pregnancy rates in the United States over the last 10 years.2 This article reports on a systematic review of the literature concerning DMPA and BMD.
Reason for concern
A 1991 study by Cundy et al3 was the first to examine the relationship between DMPA and BMD and found that DMPA users had significantly lower BMD than nonusers. DMPA delivers high doses of progestin and inhibits ovulation in most women. Consequently, DMPA can decrease serum estradiol levels. Low serum estradiol levels have also been linked to lower BMD levels in women who are in menopause or who have eating disorders.
Adolescence is a time of bone building. The chief reason for interest in the association between DMPA and decreased BMD is the potential risk of future osteoporosis and osteoporotic fractures for women using DMPA during adolescence. A mature woman’s BMD at any given time is related to her peak bone mass and subsequent rate of decline. Ninety percent of peak bone mass (the highest level of BMD achieved during one’s lifetime) is determined by age 18 in women.4 Between the ages of 18 and 30, women gain the last 10% of their maximum bone density. After age 30, bone resorption outpaces bone formation and women start to lose bone slowly.5 This decline continues until menopause, when women experience a more rapid decline in BMD related to sudden withdrawal of estrogen.
Factors that affect peak BMD. Several factors influence the level of peak bone mass a woman will reach—genetics, race, hormonal milieu, and lifestyle factors.4,5 As for lifestyle, it’s been shown that both anorexia and the female athlete triad cause low estrogen levels, and the resultant loss of BMD may not be recovered.6,7
Pregnancy, too, is known to be a state of increased bone turnover and resorption,8,9 and pregnancy during adolescence may also negatively impact BMD. A small 2002 study compared teenagers who had been pregnant with age-matched controls who had not been pregnant, and found that hip bone density in the adolescent mothers was lower by approximately 10%.10
Use of bone-affecting medications by adolescents is worrisome because they are still building bone at a high rate.
What the literature tells us
Studies of adult women. Studies examining the relationship between DMPA use and BMD have yielded varying results ( TABLE 1 ). Most of them show that using DMPA over a course of 2 years decreases BMD by 5% to 10%. New users have the most significant decreases in BMD, suggesting the decline levels off after 2 years of use (SOR: B).11-13 However, most early studies were cross-sectional and small, and thus had limited power to determine causality. In addition, these trials were not randomized, and they may have suffered from bias because treatment groups were volunteers.
Three recent prospective studies12,14,15 found that bone density losses recover after discontinuation of DMPA. Kaunitz15 followed women for up to 2 years after DMPA discontinuation and found that BMD recovered almost completely (-0.2% at hip and -1.19% at lumbosacral [LS] spine at 2 years). However, only a small number of women were studied post-discontinuation for the full 2 years. Clark12 followed women for up to 18 months after discontinuation and found that those who had used DMPA still had significantly lower BMD (-4.7% at the hip and -2.9% at the spine).