Theca Cell Function in Women With Polycystic Ovary Syndrome (PCOS)

Study Overview
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Brief Summary
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The mechanism for increased androgen production in women with polycystic ovary syndrome (PCOS) is not well understood. Excess androgen production by the ovary is stimulated by increased pituitary luteinizing hormone (LH) secretion in this disorder. The investigators hypothesize that in PCOS women ovarian theca cells, which are responsible for androgen synthesis, are more sensitive to LH stimulation compared to that of theca cells from normal women. To test this hypothesis, the investigators propose to conduct a dose-response study in which androgen responses to multiple doses of human chorionic gonadotgropin (hCG), an LH surrogate, will be assessed in PCOS and normal women.

Detailed Description
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Each subject (normal and PCOS women) will be admitted to the UCSD General Clinical Research Center (GCRC) for study on 5 occasions. All subjects will receive an intravenous injection of hCG dose of 1, 10, 25, 100, and 250 micrograms, each of which will be given on one of 5 different days each separated by at least two weeks at 8 AM. Blood samples will be obtained at t -0.5, 0, and 24 hours after injection. All visits to the GCRC will be done as out patients. The total amount of blood withdrawn will be about 35 teaspoons. For normal control subjects this will be over a period of about 4-6 months and for PCOS subjects this will be over a period of about 6-10 weeks.

Official Title
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Theca Cell Function in Women With Polycystic Ovary Syndrome

Conditions
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Polycystic Ovary Syndrome

Intervention / Treatment
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* Drug: recombinant human chorionic gonadotropin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Normal CBC (Hemoglobin must be at least 11mg/dl) Normal renal and liver function tests Normal vital signs including normal blood pressure Exclusion Criteria: No oral contraceptives No insulin lowering drugs No anti-androgens (i.e., spironolactone, flutamide, finasteride, etc) No medications that will influence androgen metabolism or clearance No medications that will inhibit the cytochrome P450 enzyme system (cimetidine, ketoconozole, etc) No use of clomiphene citrate within 3 months prior to study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: PCOS group<br>Each subject will receive a dose (1, 10, 25, 100, or 250 micrograms) of recombinant human chorionic gonadotropin administered iv on 5 separate occasions. | Drug: recombinant human chorionic gonadotropin<br>* Each subject will receive a dose (1, 10, 25, 100, or 250 micrograms) of human chorionic gonadotropin administered intravenously on 5 separate occasions.<br>* Other names: Ovidrel;|
| Active Comparator: Control group<br>Each subject will receive a dose (1, 10, 25, 100, or 250 micrograms) of recombinant human chorionic gonadotropin administered iv on 5 separate occasions. | Drug: recombinant human chorionic gonadotropin<br>* Each subject will receive a dose (1, 10, 25, 100, or 250 micrograms) of human chorionic gonadotropin administered intravenously on 5 separate occasions.<br>* Other names: Ovidrel;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum 17OHP Responses to hCG | Assess serum 17OHP levels following each dose of hCG adminstration in PCOS and normal subjects | 24 hrs post dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum Testosterone Responses to hCG | Mean serum testosterone levels before and after hCG injection. Serum testosterone levels before (-0.5 and 0 hrs) were averaged to achieve a single value | -0.5, 0, 24 hrs | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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polycystic ovary syndrome, androgens, ovary, LH