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

Phase 3

Completed

Brief Summary: 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: 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 The total amount of blood withdrawn will be about 35 teaspoons.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.

Recruitment & Eligibility

Inclusion Criteria

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

Arm && Interventions

Group	Intervention	Description
PCOS group	recombinant human chorionic gonadotropin	Each subject will receive a dose (1, 10, 25, 100, or 250 micrograms) of recombinant human chorionic gonadotropin administered iv on 5 separate occasions.
Control group	recombinant human chorionic gonadotropin	Each subject will receive a dose (1, 10, 25, 100, or 250 micrograms) of recombinant human chorionic gonadotropin administered iv on 5 separate occasions.

Primary Outcome Measures

Name	Time	Method
Serum 17OHP Responses to hCG	24 hrs post dose	Assess serum 17OHP levels following each dose of hCG adminstration in PCOS and normal subjects

Secondary Outcome Measures

Name	Time	Method
Serum Testosterone Responses to hCG	-0.5, 0, 24 hrs	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