Effect of Short Term Ovarian Suppression on Androgen Overproduction in Overweight Girls With Androgen Excess

Study Overview
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Brief Summary
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This study will test whether short-term suppression of ovarian function can ameliorate androgen (male hormone) overproduction in overweight girls with androgen excess. The investigators hypothesize that one dose of depot leuprolide agonist administration will improve androgen levels in girls with ovarian androgen overproduction. Specifically, this intervention will improve androgen levels after ovarian stimulation testing with recombinant human chorionic gonadotropin (rhCG).

Official Title
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Effect of Short Term Ovarian Suppression on Androgen Overproduction in Overweight Girls With Androgen Excess (CBS007)

Conditions
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Hyperandrogenemia, Obesity, Polycystic Ovary Syndrome

Intervention / Treatment
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* Drug: Leuprolide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: overweight (>85th BMI%) females Early to late puberty (expected age range 7-18) Hyperandrogenemic (free testosterone greater than 2.5 standard deviations above the mean for normal control subjects of the same Tanner Stage) Screening labs within age-appropriate normal range, with the exception of a mildly low hematocrit (see below) and the hormonal abnormalities inherent in obesity which could include mildly elevated luteinizing hormone (LH), lipids, testosterone, prolactin, DHEAS, E2, glucose, and insulin and decreased follicle-stimulating hormone (FSH) and/or sex hormone-binding globulin (SHBG) Exclusion Criteria: Screening labs outside of age-appropriate normal range Hemoglobin <12 mg/dL and hematocrit<36% (Subjects will be offered the opportunity to take iron supplementation for 60 days if their hematocrit is slightly low (33-36%) (suggestive of iron deficiency anemia) and will then return for retesting of their hemoglobin/hematocrit. If still <36%, they will be excluded.) Morning Cortisol <5 g/dL 17-hydroxyprogesterone >295 ng/dL History of Cushing's syndrome or adrenal insufficiency Pregnant

Ages Eligible for Study
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Minimum Age: 7 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: leuprolide<br>leuprolide 11.25 mg IM with adrenal suppression/stimulation testing with dexamethasone/Cortrosyn and ovarian stimulation testing with r-hCG before and 3 weeks after injection | Drug: Leuprolide<br>* depot leuprolide 11.25 mg if less than or equal to 37.5 kg or 15 mg if > 37.5 kg im once<br>* Other names: Depot Lupron;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 17 hydroxyprogesterone responses to rhCG before and 4 weeks after depot leuprolide administration |  | 4 weeks after leuprolide | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ovarian hormone precursor responses to rhCG before and 4 weeks after depot leuprolide administration |  | 4 weeks after leuprolide |