The effect of gonadal and adrenal steroid therapy on skeletal health in adolescents and young women with anorexia nervosa

Abstract

Anorexia nervosa (AN) is characterized by subnormal estrogen and dehydroepiandrosterone (DHEA) levels. We sought to determine whether the combination of DHEA + estrogen/progestin is superior to placebo in preserving skeletal health over 18 months in AN. Females with AN, aged 13 to 27 years, were recruited for participation in this double-blind, placebo-controlled, randomized trial. Ninety-four subjects were randomized, of whom 80 completed baseline assessments and received either study drug (oral micronized DHEA 50 mg + 20 µg ethinyl estradiol/0.1 mg levonorgestrel combined oral contraceptive pill [COC] daily; n = 43) or placebo (n = 37). Serial measurements of areal bone mineral density (aBMD), bone turnover markers, and serum hormone concentrations were obtained. Sixty subjects completed the 18-month trial. Spinal and whole-body aBMD z scores were preserved in the DHEA + COC group, but decreased in the placebo group (comparing trends, P = .008 and P = .001, respectively). Bone turnover markers initially declined in subjects receiving DHEA + COC and then returned to baseline. No differences in body composition, adverse effects of therapy, or alterations in biochemical safety parameters were observed. Combined therapy with DHEA + COC appears to be safe and effective for preventing bone loss in young women with AN, whereas placebo led to decreases in aBMD. Dehydroepiandrosterone + COC may be safely used to preserve bone mass as efforts to reverse the nutritional, psychological, and other hormonal components of AN are implemented.

Fig. 1

Patient recruitment, enrollment, and disposition.

Fig. 2

Areal BMD and aBMD z scores in adolescent and young adult females with AN randomized to 18 months of treatment with DHEA + COC or placebo. Lines represent the fitted spline ± standard error. P(trend) tests for change over time in each treatment group. P(Δtrend) compares the time course between treatment groups.

Fig. 3

Bone turnover markers and steroid hormones in adolescent and young adult females with AN randomized to 18 months of treatment with DHEA + COC or placebo. Lines represent the fitted spline ± standard error. P(Δtrend) compares the time course between treatment groups.