Polycystic Ovary Syndrome
Conditions
Keywords
polycystic ovary syndrome, androgens, ovary, LH
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 The total amount of blood withdrawn will be about 35 teaspoons.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.
Interventions
Each subject will receive a dose (1, 10, 25, 100, or 250 micrograms) of human chorionic gonadotropin administered intravenously on 5 separate occasions.
Sponsors
University of California, San Diego
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 35 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
United States
Participant flow
Recruitment details
Subjects recruited from UCSD clinics and coal advertising beginning in 2009 and ending in 2010
Pre-assignment details
Subjects involved women with PCOS and normal control women undergoing hCG stimulation
Participants by arm
| Arm | Count |
|---|---|
| PCOS Each subject will receive a dose (1, 10, 25, 100, or 250 micrograms) of hCG administered intravenously on 5 separate occasions. | 13 |
| Normal Each subject will receive a dose (1, 10, 25, 100, or 250 micrograms) of hCG administered intravenously on 5 separate occasions. | 12 |
| Total | 25 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 3 | 1 |
Baseline characteristics
| Characteristic | Normal | PCOS | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants | 13 Participants | 25 Participants |
| Age, Continuous | 30 years STANDARD_DEVIATION 1.3 | 28.5 years STANDARD_DEVIATION 1.1 | 29 years STANDARD_DEVIATION 1.2 |
| Region of Enrollment United States | 12 participants | 13 participants | 25 participants |
| Sex: Female, Male Female | 12 Participants | 13 Participants | 25 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 13 | 0 / 12 |
| other Total, other adverse events | 0 / 13 | 0 / 12 |
| serious Total, serious adverse events | 0 / 13 | 0 / 12 |
Outcome results
Primary
Serum 17OHP Responses to hCG
Assess serum 17OHP levels following each dose of hCG adminstration in PCOS and normal subjects
Time frame: 24 hrs post dose
Population: PCOS and Normal groups were analyzed according to peak 17OHP levels at each dose of r-hCG.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PCOS | Serum 17OHP Responses to hCG | 17OHP level post 25 micrograms | 2.7 ng/ml | Standard Error 0.3 |
| PCOS | Serum 17OHP Responses to hCG | 17OHP level post 100 micrograms | 3.3 ng/ml | Standard Error 0.6 |
| PCOS | Serum 17OHP Responses to hCG | 17OHP level post 250 micrograms | 4.0 ng/ml | Standard Error 0.6 |
| PCOS | Serum 17OHP Responses to hCG | 17OHP post 10 micrograms | 2.0 ng/ml | Standard Error 0.3 |
| PCOS | Serum 17OHP Responses to hCG | 17OHP level post 1 micrograms | 1.1 ng/ml | Standard Error 0.1 |
| Normal | Serum 17OHP Responses to hCG | 17OHP level post 1 micrograms | 1.0 ng/ml | Standard Error 0.1 |
| Normal | Serum 17OHP Responses to hCG | 17OHP post 10 micrograms | 1.2 ng/ml | Standard Error 0.1 |
| Normal | Serum 17OHP Responses to hCG | 17OHP level post 100 micrograms | 2.2 ng/ml | Standard Error 0.3 |
| Normal | Serum 17OHP Responses to hCG | 17OHP level post 25 micrograms | 1.7 ng/ml | Standard Error 0.2 |
| Normal | Serum 17OHP Responses to hCG | 17OHP level post 250 micrograms | 2.1 ng/ml | Standard Error 0.4 |
p-value: <0.05Mixed Models Analysis
Secondary
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
Time frame: -0.5, 0, 24 hrs
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PCOS | Serum Testosterone Responses to hCG | 0.6 ng/ml | Standard Error 0.1 |
| Normal | Serum Testosterone Responses to hCG | 0.3 ng/ml | Standard Error 0.05 |