Adrenal and Gonadal Hormone Replacement in Anorexia Nervosa
Condition: Anorexia Nervosa
MeSH terms: Anorexia; Anorexia Nervosa
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      This study seeks to gain new information on why young women with anorexia nervosa are
      predisposed to early bone loss and osteoporosis. Through a randomized treatment trial in
      which participants will receive either combined therapy with the adrenal hormone,
      dehydroepiandrosterone (DHEA) and estrogen replacement therapy or placebo, we will determine
      the effects of an 18-month treatment course on bone mass, circulating markers of bone
      turnover, and serum levels of a factor, insulin-like growth factor I (IGF-I). We are also
      studying if these therapies change bone structure to increase skeletal strength compared to
      placebo, as assessed through cross-sectional geometric analysis of our bone density data by
      dual-energy x-ray absorptiometry (DXA).
    

Detailed description: 
      Profound osteopenia is a frequent and often irreversible complication of anorexia nervosa
      (AN). Adolescents with AN often have a reduced peak bone mass and are at increased risk for
      early osteoporosis and fractures. These young women have subnormal serum levels of gonadal
      steroids and the adrenal androgen dehydroepiandrosterone (DHEA) that may be associated with
      their low bone mineral density (BMD). Low DHEA levels are accompanied by decreased levels of
      insulin-like growth factor I (IGF-I), estrogen, and testosterone. Previous data from our
      group indicate that oral DHEA therapy in young women with AN: increases lean body mass, serum
      levels of bone formation markers and insulin-like growth factor I (IGF-I), and decreases
      urinary markers of bone resorption. We also found that standard hormonal replacement therapy
      (HRT) significantly decreased bone resorption markers. Information on the effects of these
      therapies on bone strength and ultimate fracture risk is lacking.

      In this project, we will test the hypothesis that combined therapy with DHEA and
      estrogen/progestin will enhance bone mass in patients with AN through anabolic and
      antiosteolytic mechanisms. We will test the hypothesis that 18 months of DHEA + HRT will
      increase bone mineral density (BMD) and markers of bone formation, while decreasing bone
      resorption markers in these patients. The proposed study will examine whether restoring
      normal levels of DHEA and estrogen in these young women will increase bone mass during a
      critical period for bone accretion. The study will also examine whether DHEA's anabolic
      effects on bone are mediated through the skeletal IGF-I regulatory system. Using
      cross-sectional analyses of dual energy x-ray absorptiometry (DXA) data, we will also measure
      indices of bone structural geometry to determine if mechanical strength is compromised in
      these young women, and if strength is restored in response to combined
      anabolic/antiresorptive therapy.

      To gain new information on the mechanisms underlying bone loss and fracture risk in young
      women with AN, our research goals are:

      Specific Aim I: Through a randomized controlled trial, to measure the effects of an 18-month
      course of DHEA + HRT on bone mass, markers of bone turnover, and serum levels of IGF-I
      compared to placebo. Specific Aim II: To determine whether combined therapy with adrenal and
      gonadal steroid replacement changes bone structure to increase strength compared to placebo,
      as assessed through cross-sectional geometric analysis of DXA data.
    

Intervention name(s): Hormone replacement therapy (estrogen/progestin); Placebo (Sugar Pill); Dehydroepiandrosterone (DHEA)
Intervention type(s): Drug; Other; Drug
Intervention description(s): Hormone replacement therapy (estrogen/progestin). 0.3 mg conjugated estrogens x 3 months, followed by 9 months of oral contraceptive (20 mg ethinyl estradiol + 0.1 mg levonorgestrel); Placebo (sugar pill); 50 mg tablet, 1 daily
Other intervention name(s): Alesse (20 mg ethinyl estradiol + 0.1 mg levonorgestrel); Premarin (conjugated estrogens); Placebo; Sugar pill; Prasterone
Intervention MeSH terms: Levonorgestrel; Ethinyl Estradiol; Hormones; Estradiol; Estrogens, Conjugated (USP); Estrogens; Dehydroepiandrosterone; Progestins
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: anorexia nervosa; adolescents; dual-energy x-ray absorptiometry; dehydroepiandrosterone (DHEA); osteoporosis