The Effect of Estrogen-Progestin Treatment on Bone Mineral Density in Anorexia Nervosa

Introduction: Osteopenia is a serious complication of anorexia nervosa (AN). Although in other states of estrogen deficiency, estrogen replacement therapy increases bone mass, its role in AN remains unresolved. Study Objective: To study the effect of estrogen-progestin administration on bone mass in AN. Design, Setting, and Participants: A prospective observational study of 50 adolescents with AN (mean age 16.8 ± 2.3 yrs) was conducted in a tertiary referral center. Main Outcome Measures: Bone mineral density (BMD) of the lumbar spine and left hip were prospectively measured using dual-energy x-ray absorptiometry at baseline and annually. Interventions: Twenty-two subjects received estrogen-progestin and 28 standard treatment (Rx) alone. Estrogen-progestin was administered daily as an oral contraceptive containing 20–35 mcg ethinyl estradiol. All subjects received calcium supplementation and the same medical, psychological, and nutritional intervention (standard Rx). Mean length of follow-up was 23.1 ± 11.4 months. Results: At presentation, patients were malnourished (79.5% ± 7.6% IBW), hypoestrogenemic (estradiol 24.7 ± 10.7 pg/mL), and had reduced bone mass (lumbar spine BMD −2.01 ± 0.69 SD below the young adult reference mean). Ninety-two percent of subjects were osteopenic and 26% met WHO criteria for osteoporosis. Body weight, and no treatment group, was the major determinant of BMD. At one-year follow-up, there were no significant differences in absolute values or in net change of lumbar spine or femoral neck BMD between those who received estrogen-progestin and those who received standard Rx (80% power of finding a 3% difference in BMD at 1 yr). In those followed for 2–3 yrs, osteopenia was persistent and in some cases progressive. Conclusion: In our study population, estrogen-progestin did not significantly increase BMD compared with standard Rx. These results question the common practice of prescribing hormone replacement therapy to increase bone mass in AN.