Adrenal and Gonadal Hormone Replacement in Anorexia Nervosa
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|ClinicalTrials.gov Identifier: NCT00310791|
Recruitment Status : Completed
First Posted : April 5, 2006
Results First Posted : February 1, 2013
Last Update Posted : April 11, 2018
|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|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||80 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Triple (Participant, Care Provider, Investigator)|
|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|
Placebo Comparator: Sugar Pill
Placebo (sugar pill); identical to treatment medication capsule
Other: Placebo (Sugar Pill)
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)
Drug: Dehydroepiandrosterone (DHEA)
50 mg tablet, 1 daily
Other Name: Prasterone
- Areal Bone Density by DXA [ Time Frame: 18-Months ]
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 ClinicalTrials.gov identifier (NCT number): NCT00310791
|United States, Massachusetts|
|Children's Hospital Boston|
|Boston, Massachusetts, United States, 02115|
|Principal Investigator:||Catherine M. Gordon, MD||Boston Children’s Hospital|