General Obstetrics and Gynecology: Gynecology
Double-blinded randomized controlled trial of estrogen supplementation in adolescent girls who receive depot medroxyprogesterone acetate for contraception

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Objective

The purpose of this clinical trial was to evaluate the effect of estrogen supplementation on bone mineral density in adolescent girls who received depot medroxyprogesterone acetate for contraception.

Study design

One hundred twenty-three adolescents who began receiving depot medroxyprogesterone acetate injections every 12 weeks were assigned randomly to receive monthly injections of estradiol cypionate or placebo. The main outcome was bone mineral density that was measured by dual energy x-ray absorptiometry for 12 (n = 69) to 24 (n = 36) months. Participants, technicians, and physicians were blinded to estrogen treatment.

Results

Over the 24-month period, the percentage of change from baseline bone mineral density at the lumbar spine was 2.8% in the estradiol cypionate group versus −1.8% in the placebo group (P <.001). At the femoral neck, the percentage of change from baseline bone mineral density was 4.7% in the estradiol cypionate group versus −5.1% in the placebo group (P <.001).

Conclusion

Our results suggest that estrogen supplementation is protective of bone in adolescent girls who receive depot medroxyprogesterone acetate injections.

Section snippets

Material and methods

The study population was drawn from 4 general adolescent health clinics that are located in a large, metropolitan setting between May 2000 and December 2002. Adolescent girls, who ranged in age from 12 to 18 years, who were seeking contraception, and who selected DMPA for their method of contraception were eligible for enrollment. Exclusion criteria included the use of DMPA, pregnancy or abortion over the past 6 months, the use of oral contraceptives over the past 3 months, a chronic medical

Results

At baseline, the study population comprised 123 adolescent girls who selected DMPA as their contraceptive method; 65 girls were assigned randomly to the DMPA-estrogen (DMPA-E) group, and 58 girls were assigned randomly to the DMPA-placebo (DMPA-P) group. In December 2003, the Data Safety Monitoring Board supervised interim analysis of the trial with the recommendation that, if our spine BMD findings at 12 months were significantly different between the 2 treatment groups at a probability value

Comment

In this randomized clinical trial, we found that adolescents who were receiving DMPA-E had significantly higher BMD at both the lumbar spine and femoral neck at 12 and 24 months compared with that seen in girls who were receiving DMPA-P. When the data were adjusted for volumetric changes in bone size, the findings followed a similar pattern at the lumbar spine at 12 and 24 months and the femoral neck at 24 months. The only other randomized controlled clinical trial of estrogen supplementation

Acknowledgments

We thank the following team members for their exceptional efforts: Kelly Camlin-Shingler, MSSA, Ray Harvey, BS, Mary Jo Day, LPN, Darlene Lewis, RN, Rachel Whitsel, BA.

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    Supported by National Institutes of Health grant R01HD39009 and General Clinical Research Center grant M1RR00080I2.

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