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Adrenal and Gonadal Hormone Replacement in Anorexia Nervosa

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00310791
Recruitment Status : Completed
First Posted : April 5, 2006
Results First Posted : February 1, 2013
Last Update Posted : April 11, 2018
United States Department of Defense
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
Catherine M. Gordon, Boston Children's Hospital

Brief 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).

Condition or disease Intervention/treatment Phase
Anorexia Nervosa Drug: Hormone replacement therapy (estrogen/progestin) Other: Placebo (Sugar Pill) Drug: Dehydroepiandrosterone (DHEA) Phase 2 Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 80 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Effects of Adrenal and Gonadal Hormone Replacement in Young Women With Anorexia Nervosa
Study Start Date : April 2004
Actual Primary Completion Date : October 2009
Actual Study Completion Date : December 2010

Resource links provided by the National Library of Medicine

Drug Information available for: Estrogens

Arm Intervention/treatment
Placebo Comparator: Sugar Pill
Placebo (sugar pill); identical to treatment medication capsule
Other: Placebo (Sugar Pill)
Placebo (sugar pill)
Other Names:
  • Placebo
  • Sugar pill

Experimental: DHEA + Hormone replacement therapy (estrogen/progestin)
Combined therapy of dehydroepiandrosterone (DHEA) and hormone replacement therapy (ERT). Patients randomized to the DHEA + HRT arm will receive micronized oral DHEA in a dose of 50 mg daily + HRT (0.3 mg Premarin, 1 tablet daily for 3 months, follow by Alesse (20 mg ethinyl estradiol + 0.1 mg levonorgestrel for 15 months). The estrogen/progestin component of the regimen has been chosen to maximize patient compliance, as patients with AN may experience bloating or nausea if higher estrogen doses (> 20 g) are initiated too rapidly. The DHEA capsule strength will be 50 mg, the total daily dose to be studied in combination with HRT. The micronized DHEA preparation achieves more constant DHEA and DHEA-S levels. Fifty milligrams appears to be a physiological replacement dose for these young women, determined both from our pilot (10) and longitudinal studies (7).
Drug: Hormone replacement therapy (estrogen/progestin)
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)
Other Names:
  • Alesse (20 mg ethinyl estradiol + 0.1 mg levonorgestrel)
  • Premarin (conjugated estrogens)

Drug: Dehydroepiandrosterone (DHEA)
50 mg tablet, 1 daily
Other Name: Prasterone

Primary Outcome Measures :
  1. Areal Bone Density by DXA [ Time Frame: 18-Months ]

Information from the National Library of Medicine

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Ages Eligible for Study:   15 Years to 30 Years   (Child, Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Age 15 - 30 years
  • Anorexia nervosa by psychiatric criteria
  • Amenorrhea for at least 3 months

Exclusion Criteria:

  • Receiving no medications known to affects bone metabolism
  • No other chronic medical conditions

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00310791

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United States, Massachusetts
Children's Hospital Boston
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Boston Children's Hospital
United States Department of Defense
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
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Principal Investigator: Catherine M. Gordon, MD Boston Children's Hospital
Publications of Results:

Other Publications:
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Responsible Party: Catherine M. Gordon, Catherine Gordon, MD, MSc, Boston Children's Hospital Identifier: NCT00310791    
Obsolete Identifiers: NCT01343771
Other Study ID Numbers: Anorexia04
R01HD043869 ( U.S. NIH Grant/Contract )
First Posted: April 5, 2006    Key Record Dates
Results First Posted: February 1, 2013
Last Update Posted: April 11, 2018
Last Verified: March 2018
Keywords provided by Catherine M. Gordon, Boston Children's Hospital:
anorexia nervosa
dual-energy x-ray absorptiometry
dehydroepiandrosterone (DHEA)
Additional relevant MeSH terms:
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Anorexia Nervosa
Signs and Symptoms, Digestive
Feeding and Eating Disorders
Mental Disorders
Ethinyl Estradiol
Estrogens, Conjugated (USP)
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Contraceptive Agents, Hormonal
Contraceptive Agents
Reproductive Control Agents
Contraceptive Agents, Female
Contraceptives, Oral, Synthetic
Contraceptives, Oral
Contraceptives, Oral, Hormonal
Adjuvants, Immunologic
Immunologic Factors