PCOS
Conditions
Keywords
PCOS, oligomenorrhea, irregular menses, hyperandrogenemia, elevated testosterone, adolescents, androgens, ovary, LH
Brief summary
In women with polycystic ovary syndrome (PCOS), the cardinal physiological abnormality is excessive ovarian androgen production marked by increased serum testosterone (T) and androstenedione (A) levels. Studies to determine the alteration in ovarian steroidogenesis that lead to abnormal production of ovarian androgens have revealed increased CYP17 gene expression with accentuated 17-hydroxylase activity leading to exaggerated 17-hydroxyprogesterone (17P) responses to luteinizing hormone (LH) stimulation. In contrast, T and A responses did not distinguish between PCOS and normal women, although these androgens were clearly greater in the former compared to the latter group. As a result, 17P responsiveness has been employed to determine the functional capacity of the ovary to produce androgens. The stimulatory agents that have been used included GnRH agonist, Lupron, at a dose of 10 microgram per kilogram, or hCG at a dose of 10,000 IU. The investigators propose to conduct a study that will determine the pattern of androgen responsiveness to 25ucg of hCG after 24 hours in adolescents with PCOS, those with oligomenorrhea, and in normal controls. This will allow for a comparison of these adolescents' ovarian functional capacity to produce androgens.
Detailed description
In women with polycystic ovary syndrome (PCOS), the cardinal physiological abnormality is excessive ovarian androgen production marked by increased serum testosterone (T) and androstenedione (A) levels. Studies to determine the alteration in ovarian steroidogenesis that lead to abnormal production of ovarian androgens have revealed increased CYP17 gene expression with accentuated 17-hydroxylase activity leading to exaggerated 17-hydroxyprogesterone (17P) responses to luteinizing hormone (LH) stimulation. In contrast, T and A responses did not distinguish between PCOS and normal women, although these androgens were clearly greater in the former compared to the latter group. As a result, 17P responsiveness has been employed to determine the functional capacity of the ovary to produce androgens. The stimulatory agents that have been used included GnRH agonist, Lupron, at a dose of 10 microgram per kilogram, or hCG at a dose of 10,000 IU.We propose to conduct a study that will determine the pattern of androgen responsiveness to 25ucg of hCG after 24 hours in adolescents with PCOS, those with oligomenorrhea, and in normal controls. This will allow for a comparison of these adolescents' ovarian functional capacity to produce androgens.
Interventions
DRUGDexamethasone
Each subject in each group will receive 1 mg of oral dexamethasone in the evening and return in the morning for an injection of 25ug of IV recombinant human chorionic gonadotropin. Subjects will also have blood drawn at times -0.5, 0, 0.5, and 24 hours after the injection of r-hCG for measurement of steroid hormones.
Each subject in each group will receive 1 mg of oral dexamethasone in the evening and return in the morning for an injection of 25ug of IV recombinant human chorionic gonadotropin (r-hCG). Subjects will also have blood drawn at times -0.5, 0, 0.5, and 24 hours after the injection of r-hCG for measurement of steroid hormones.
Sponsors
University of Virginia
University of California, San Diego
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
12 Years to 18 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
* Pregnancy * On oral contraceptives * On insulin lowering drugs * On anti-androgens (i.e., spironolactone, flutamide, finasteride, etc) * On medications that will influence androgen metabolism or clearance * On medications that will inhibit the cytochrome P450 enzyme system (Cimetidine, ketoconazole, etc)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 17OHP Levels After hCG | 24 hours | Assess serum levels of 17OHP after stimulation with recombinant hCG |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Testosterone | 24 hours | Assess seruim levels of testosterone after stimulation with recombinant hCG |
| Androstenedione | 24 hours | Assess serum levels of androstenedione after stimaultion with recombinant hCG |
| DHEA | 24 hours | Assess serum levels of DHEA after stimulation with recombinant hCG |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| PCOS Group Intervention: Each subject in the PCOS group will receive 1 mg of oral dexamethasone in the evening and return in the morning for an injection of 25ug of IV recombinant human chorionic gonadotropin. Subjects will also have blood drawn at times -0.5, 0, 0.5, and 24 hours after the injection of r-hCG for measurement of steroid hormones. | 14 |
| Normal Group Intervention: Each subject in the Normal group will receive dexamethasone 1 mg orally in the evening and return the next morning for an injection of 25ug of IV recombinant human chorionic gonadotropin. Subjects will the have blood drawn at -0.5, 0, 0.5, and 24 hours after hCG injection for steroid hormone measurements. | 10 |
| Oligomenorrhea Group | 0 |
| Total | 24 |
Baseline characteristics
| Characteristic | PCOS Group | Normal Group | Total |
|---|---|---|---|
| Age, Continuous | 14.9 years STANDARD_DEVIATION 1 | 15.4 years STANDARD_DEVIATION 1.2 | 15.3 years STANDARD_DEVIATION 1 |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Sex: Female, Male Female | 14 Participants | 10 Participants | 24 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 14 | 0 / 10 | 0 / 0 |
| other Total, other adverse events | 0 / 14 | 0 / 10 | 0 / 0 |
| serious Total, serious adverse events | 0 / 14 | 0 / 10 | 0 / 0 |
Outcome results
Primary
17OHP Levels After hCG
Assess serum levels of 17OHP after stimulation with recombinant hCG
Time frame: 24 hours
Population: Oligmenorhea group not included in study
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PCOS Group | 17OHP Levels After hCG | 3.2 ng/ml | Standard Error 0.5 |
| Normal Group | 17OHP Levels After hCG | 1.3 ng/ml | Standard Error 0.3 |
Secondary
Androstenedione
Assess serum levels of androstenedione after stimaultion with recombinant hCG
Time frame: 24 hours
Population: Oligomenorreha group not inlcuded in study
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PCOS Group | Androstenedione | 2.1 ng/ml | Standard Error 0.2 |
| Normal Group | Androstenedione | 0.9 ng/ml | Standard Error 0.2 |
Secondary
DHEA
Assess serum levels of DHEA after stimulation with recombinant hCG
Time frame: 24 hours
Population: Oligomenrrhea group not included in study
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PCOS Group | DHEA | 1.6 ng/ml | Standard Error 0.2 |
| Normal Group | DHEA | 1.0 ng/ml | Standard Error 0.2 |
Secondary
Testosterone
Assess seruim levels of testosterone after stimulation with recombinant hCG
Time frame: 24 hours
Population: Oligpmenrreha group not included in study
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PCOS Group | Testosterone | 1.6 ng/ml | Standard Error 0.2 |
| Normal Group | Testosterone | 1.0 ng/ml | Standard Error 0.2 |