Hormonal Therapy for Teens With Anorexia Nervosa

• BMD by DXA (spine, hip, whole body) [ Time Frame: Baseline; M6; M12 ] [ Designated as safety issue: No ]
• Bone biomarkers [ Time Frame: Baseline; M3; M6; M9; M12 ] [ Designated as safety issue: No ]
• BMD by pQCT of tibia [ Time Frame: Baseline; M6; M12 ] [ Designated as safety issue: No ]
• Hormonal panel (serum) [ Time Frame: Baseline; M3; M6; M9; M12 ] [ Designated as safety issue: No ]

The following randomized controlled trial will examine the effects of one year of dehydroepiandrosterone and estrogen replacement therapy (DHEA +ERT) on bone mineral density (BMD) and bone marrow composition in adolescents with anorexia nervosa (AN). The investigators will use imaging techniques including dual-energy x-ray absorptiometry (DXA), peripheral quantitative computed tomography (pQCT), visual assessments of magnetic resonance imaging (MRI) data, MR relaxometry and magnetic resonance spectroscopy (MRS) to measure bone mineral density and evaluate bone marrow composition. The investigators will also collect serum to measure hormonal mediators of the changes observed in both bone density and bone marrow composition, including adrenal and gonadal steroids, insulin-like growth factors, growth hormone, and ghrelin, adiponectin, and leptin.

This double-blinded randomized controlled trial will include 2 treatment arms of 35 patients. Group 1 will receive micronized oral DHEA in a dose of 50 mg daily + ERT (0.3 mg Premarin, 1 tablet daily for 3 months, follow by Alesse, 20 mg ethinyl estradiol + 0.1 mg levonorgestrel for 9 months); and Group 2 will receive placebo.There will be 12 months of therapy with follow up assessments every 3 months. DXA and pQCT measurements will be obtained at baseline, 6 months, and 12 months; MRI and MRS will be performed at baseline and 1 year; serum samples will be obtained at baseline and every 3 months throughout the 12-month trial; psychological and nutrition surveys will be carried out at baseline, 6, and 12 months.

The investigators anticipate that this study will enable us to evaluate the efficacy of oral DHEA + ERT as a treatment strategy to optimize peak bone mass and to prevent development of osteoporosis in patients with AN.

• Drug: DHEA (Prasterone) + ERT (Aviane)
  Micronized oral DHEA in a dose of 50 mg daily + ERT (0.3 mg Premarin, 1 tablet daily for 3 months, follow by Alesse, 20 mcg ethinyl estradiol + 0.1 mg levonorgestrel for 9 months)
  Other Names:

  • Dehydroepiandrosterone (DHEA)
  • Estrogen Replacement Therapy (ERT)
• Other: Placebo
  A placebo tablet will be developed by the Children's Hospital Pharmacy. Both treatments (DHEA+ERT and placebo) will be administered in a gelatin capsule.
  Other Name: Sugar Pill

• Placebo Comparator: Placebo
  Intervention: Other: Placebo
• Active Comparator: DHEA + ERT
  Intervention: Drug: DHEA (Prasterone) + ERT (Aviane)

• Ecklund K, Vajapeyam S, Feldman HA, Buzney CD, Mulkern RV, Kleinman PK, Rosen CJ, Gordon CM. Bone marrow changes in adolescent girls with anorexia nervosa. J Bone Miner Res. 2010 Feb;25(2):298-304.
• Shaughnessy BF, Feldman HA, Cleveland R, Sonis A, Brown JN, Gordon CM. Oral health and bone density in adolescents and young women with anorexia nervosa. J Clin Pediatr Dent. 2008 Winter;33(2):87-92.
• DiVasta AD, Ringelheim J, Bristol SK, Feldman HA, Gordon CM. Skeletal measurements by quantitative ultrasound in adolescents and young women with anorexia nervosa. J Pediatr. 2007 Mar;150(3):286-90, 290.e1.
• DiVasta AD, Beck TJ, Petit MA, Feldman HA, LeBoff MS, Gordon CM. Bone cross-sectional geometry in adolescents and young women with anorexia nervosa: a hip structural analysis study. Osteoporos Int. 2007 Jun;18(6):797-804. Epub 2007 Jan 5.
• Gordon CM, Grace E, Emans SJ, Feldman HA, Goodman E, Becker KA, Rosen CJ, Gundberg CM, LeBoff MS. Effects of oral dehydroepiandrosterone on bone density in young women with anorexia nervosa: a randomized trial. J Clin Endocrinol Metab. 2002 Nov;87(11):4935-41.
• Gordon CM, Goodman E, Emans SJ, Grace E, Becker KA, Rosen CJ, Gundberg CM, Leboff MS. Physiologic regulators of bone turnover in young women with anorexia nervosa. J Pediatr. 2002 Jul;141(1):64-70.

Inclusion Criteria:

• age 11-17 years (potential subjects age 11-13 years must have a bone age x-ray (obtained within previous 6 months) that is 13 years or more advanced)
• diagnosis of AN based on DSM-IV criteria
• female gender
• postmenarchal

Exclusion Criteria:

• concomitant chronic diseases which affect bone health (e.g., cystic fibrosis, celiac disease)
• use of medications known to affect bone metabolism during the last 3 months
• use of depot medroxyprogesterone acetate during the last 12 months
• current pregnancy