The effect of estrogen-progestin treatment on bone mineral density in anorexia nervosa

J Pediatr Adolesc Gynecol. 2002 Jun;15(3):135-43. doi: 10.1016/s1083-3188(02)00145-6.


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.

Publication types

  • Clinical Trial
  • Comparative Study

MeSH terms

  • Adolescent
  • Adult
  • Anorexia Nervosa / complications*
  • Anorexia Nervosa / therapy
  • Bone Density / drug effects*
  • Bone Diseases, Metabolic / etiology*
  • Bone Diseases, Metabolic / prevention & control*
  • Estrogen Replacement Therapy*
  • Estrogens / therapeutic use*
  • Female
  • Humans
  • Progestins / therapeutic use*
  • Prospective Studies
  • Treatment Failure


  • Estrogens
  • Progestins