Studies have linked use of depot medroxy-progesterone acetate (DMPA) contraception with accelerated bone loss, but no prospective studies have compared this bone loss to that experienced by adult women using other forms of contraception and to those not using hormone contraceptives. Berenson and colleagues studied the influence of contraceptive medications on bone mineral density.

A total of 155 healthy volunteers aged 18 to 33 years who met criteria for active military service were included in the study. None of the participants was using hormone contraceptives or had any known contraindications to contraceptive use at the beginning of the study. Seventy-one women not using hormone contraceptives were recruited as control subjects. Women in the study groups selected either DMPA (150 mg injected every three months) or oral contraception. Participants selecting oral contraception were randomly assigned to use either 0.035 mg ethinyl estradiol/1 mg norethindrone or 0.030 ethinyl estradiol/0.15 mg desogestrel. Baseline data obtained for all participants included body mass index, smoking history, exercise habits, and estimated calcium intake. Scans for bone mineral density of the lumbar spine were performed at the beginning of the study and repeated 10 to 14 months later.

Initially, 96 women chose DMPA, 87 women used the norethindrone formula, and 92 women used the desogestrel formula. The groups were comparable, although smoking was more common in the DMPA group (51.5 percent) and among control subjects (42.4 percent) than in either of the groups using oral contraceptives (17.9 percent and 25.7 percent). Calcium intake was low in all groups (daily mean, 565 mg), although most women exercised regularly, and none were obese. More than one third of participants discontinued their selected contraceptive method during the year, and an additional 31 women did not obtain scans. Results were reported for 96 users of hormone contraception and 59 control subjects.

The mean bone loss in DMPA users was 2.74 percent, compared with a mean loss of 0.37 percent in control subjects. Conversely, women using norethindrone-containing pills had a mean gain of 2.33 percent, and those using desogestrel-containing pills had a mean gain of 0.33 percent. These effects on bone mineral density remained significant even when controlling for demographic factors and smoking.

The authors conclude that DMPA use for 12 months is associated with a loss of bone mineral density, whereas oral contraceptive use is associated with gains in bone strength. They relate this effect to low serum levels of ethinyl estradiol and call for further studies. In particular, the reversibility of the DMPA effect needs to be determined.