Question

• In amenorrheic females with anorexia nervosa, does estrogen therapy, compared to no hormonal therapy, increase bone density?

Clinical Bottom Lines

1. In this patient population, estrogen therapy does not significantly increase measurements of spinal bone mineral density.
2. Bone mineral density is improved with recovery of normal menses and a more normal body weight.
3. Hormone replacement is not an easy solution to one of the many problems of anorexia nervosa.

Summary of Key Evidence

1. 48 amenorrheic patients with anorexia nervosa were studied.(1) 22 patients received estrogen and progesterone, and 26 patients acted as control subjects.
2. Within the therapy group, the type of hormonal therapy varied; some patients took oral contraceptive pills, and others received Premarin (0.625mg) and Provera (5 mg).
3. Patients were followed every 6 months for an average of 18 months. History and physical, spinal bone density, and serum studies were performed at each visit.
4. All patients took at least 1500 mg of calcium per day (from diet and/ or supplements).
5. The two groups were similar in all ways at the onset of the study, including mean spinal bone mineral density.
6. There was no statistical difference in bone density between the two groups at the end of the study period. (p=0.2)
7. There was a statistically significant increase in mean bone density in the subset of the control group who regained menses and a more normal body weight.
8. No mention of the power of this study is made and there are several factors (e.g. different types of hormonal therapy) which could bias the study in the direction of no results.

Additional Comments

• There were many confounders in this study, including: different hormone therapies within the study group; some patients recovered toward normal body weight, and others did not; amount of exercise performed by patients is not recorded or considered; and only spinal bone density is considered.
• The increase in bone density found in the subset group does not meet evidence based medicine criteria for validity.
• Assumption that spinal bone density measurement correlates clinically with risk of fracture.
• Women with decreased bone density, increased exercise, and normal weight do seem to respond to estrogen, suggesting that a different mechanism is in effect in women with anorexia nervosa.

Citation

1. Klibanski A, et al. The effects of estrogen administration on trabecular bone loss in young women with anorexia nervosa. J Clin Endocrinol Metab 1995; 80(3): 898-904.

CAT Author: Amy Morrow, MD

CAT Appraisers: John G. Frohna, MD

Date appraised: January 29, 2001