Mechanisms of Increased Androgen Production Among Women With Polycystic Ovary Syndrome

• Sponsor: University of California, San Diego (Other)
• Overall Status: Completed
• CT.gov ID: NCT00989781
• Collaborator: (none)
• Enrollment: 41
• Location: 1
• Arms: 2
• Duration (Months): 48
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

Jeffrey Chang MD is conducting a research study to learn more about the increased male hormone levels, otherwise known as androgens, seen in women with polycystic ovary syndrome (PCOS). Women with PCOS have ovaries that are comprised of many cysts, or follicles. They also have irregular or absent menstrual periods and symptoms of increased male hormones, such as facial hair or acne. In each part of the study (except part 4 which is for PCOS women only) we will be comparing responses of PCOS women to normal controls

Condition or Disease	Intervention/Treatment	Phase
Polycystic Ovary Syndrome	Radiation: 3-D Ultrasound; Drug: recombinant human chorionic gonadotropin; Drug: Recombinant human follicle stimulating hormone; Drug: Adrenocorticotropin; Drug: Dexamethasone; Drug: Glucose	N/A

Detailed Description

The first part of this study looks specifically at the structure of the ovaries, which are the female sex glands where both androgens and estrogens (female hormones) are made. It involves imaging your ovaries with a technology called 3-D Ultrasound. We are interested in recording the number, size and arrangement of the follicles in your ovaries.

The second part of the study looks at how the ovary produces male hormones, or androgens, with and without follicle stimulating hormone (FSH) stimulation. Hormones are substances made by a gland in one part of the body which regulate another part. FSH is a hormone naturally produced by the pituitary gland located in the brain and it helps the ovary produce estrogens, or female hormones. LH is a hormone also naturally produced by the pituitary gland and it has the ability to stimulate the ovary to make androgens. We are interested to see how much androgen your ovaries will produce in response to LH with and without FSH. To accomplish this, you will be given FSH as well as hCG, a drug that acts like LH to stimulate the ovary; FSH and hCG are approved by the Food and Drug Administration (FDA) for this investigational, off-label use.

The third part of the study looks at how much the adrenal glands contribute to the increase male hormone levels seen in PCOS. ACTH is a hormone naturally produced by the pituitary gland located in the brain and it stimulates the adrenals to make hormones. The adrenal glands are above the kidneys. They are chiefly responsible for helping the body adjust to stressful situations and work by producing cortisol and adrenaline. The adrenal glands also produce androgens, or male hormones. Previous studies have shown that some women with PCOS produce more male hormones from their adrenals. We are interested to see how much androgen your adrenal glands produce. To accomplish this, you will first be given dexamethasone, a stress steroid, to temporarily suppress your adrenal glands. You will then be given ACTH intravenously over the course of 7 hours to stimulate your adrenal glands.

The fourth part of the study is for PCOS women only and looks at how much the role of insulin contributes to the increase male hormone levels. Insulin is a hormone naturally produced by the pancreas that stimulates all of the cells in your body to take up glucose, or sugar, from the blood. Previous studies have shown that PCOS women who are more resistant to insulin, or whose cells do not take up glucose from the blood in response to insulin, make more male hormones. We are interested to see how much androgen your ovaries produce in response to LH before and after we temporarily decrease the amount of insulin in your blood. To accomplish this, you will again be given hCG, a drug that acts like LH to stimulate the ovary, with and without diazoxide, a drug that decreases the amount of insulin in your bloodstream. These tests will all be done after you are on a diet that limits how much sugar you eat. To test how much insulin you make, you will also be given Oral Glucose Tolerance Tests before and after diazoxide. This test is done by drinking a sugary liquid and testing your blood over 3 hours.

Study Design

• Study Type: Interventional
• Actual Enrollment: 41 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Screening
• Official Title: Mechanisms of Increased Androgen Production Among Women With Polycystic Ovary Syndrome
• Study Start Date: Sep 1, 2009
• Actual Primary Completion Date: Sep 1, 2013
• Actual Study Completion Date: Sep 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: PCOS women Each subject will undergo pelvic 3D ultrasound followed by an iv recombinant human chorionic gonadotropin (r-hCG) stimulation test. One month later the r-hCG test will be repeated 24 hr after an injection of recombinant human follicle stimulating hormone (FSH). After 1 month, subjects will receive a 7 hr dose-response infusion of adrenocorticotropin (ACTH) with blood sampling. Dexamethasone will be given prior to ACTH. After 1 month, subject will receive r-hCG as described above followed the next day by an oral glucose tolerance test (OGTT). Subsequently, subjects will take Diazoxide 3 times a day for 2 weeks. At weekly intervals (2 weeks), the r-hCG stimulation test will be repeated followed the next day by an OGTT as described above.	Radiation: 3-D Ultrasound; One time pelvic ultrasound; Drug: recombinant human chorionic gonadotropin; Recombinant human chorionic gonadotropin will be given iv and blood samples obtained before and 24 hr afterwards; Other Names: Ovidrel r-hCG ; Drug: Recombinant human follicle stimulating hormone; Recombinant human follicle stimulating hormone will be given iv and blood samples obtained before and 24 hr later.; Other Names: Gonal-F r-hFSH ; Drug: Adrenocorticotropin; Each subject will receive a 7 hr dose-response infusion of Adrenocorticotropin.; Other Names: Cosyntropin ACTH ; Drug: Dexamethasone; Dexamethasone will be given prior to ACTH infusion test.; Other Names: corticosteroid ; Drug: Glucose; Each subject will undergo 3 oral glcuose tolerance tests.; Other Names: sugar
Experimental: Normal women Each subject will undergo pelvic 3D ultrasound followed by an iv recombinant human chorionic gonadotropin (r-hCG) stimulation test. One month later the r-hCG test will be repeated 24 hr after an injection of recombinant human follicle stimulating hormone (FSH). After 1 month, subjects will receive a 7 hr dose-response infusion of adrenocorticotropin (ACTH) with blood sampling. Dexamethasone will be given prior to ACTH. After 1 month, subject will receive r-hCG as described above followed the next day by an oral glucose tolerance test (OGTT). Subsequently, subjects will take Diazoxide 3 times a day for 2 weeks. At weekly intervals (2 weeks), the r-hCG stimulation test will be repeated followed the next day by an OGTT as described above.	Radiation: 3-D Ultrasound; One time pelvic ultrasound; Drug: recombinant human chorionic gonadotropin; Recombinant human chorionic gonadotropin will be given iv and blood samples obtained before and 24 hr afterwards; Other Names: Ovidrel r-hCG ; Drug: Recombinant human follicle stimulating hormone; Recombinant human follicle stimulating hormone will be given iv and blood samples obtained before and 24 hr later.; Other Names: Gonal-F r-hFSH ; Drug: Adrenocorticotropin; Each subject will receive a 7 hr dose-response infusion of Adrenocorticotropin.; Other Names: Cosyntropin ACTH ; Drug: Dexamethasone; Dexamethasone will be given prior to ACTH infusion test.; Other Names: corticosteroid ; Drug: Glucose; Each subject will undergo 3 oral glcuose tolerance tests.; Other Names: sugar

Outcome Measures

Primary Outcome Measures

1. 17-hydroxyprogesterone Responses to hCG in PCOS Women and Normal Controls [Baseline and 24 hours after hCG]

   Change from baseline in 17-hydroxyprogesterone at 24 hours after hCG injection

Secondary Outcome Measures

1. Adrenal 17-hydroxyprogesterone Response to ACTH in PCOS Women and Normal Controls [Baseline and 1, 2, 3, 4, 5, and 6 hours after ACTH]

   17-hydroxyprogesterone response to ACTH infusion in women with PCOS and normal women. Response is reported as a single value generated by summing the data at end time frame.

2. 17 Hydroxyprogesterone Response to hCG Injection After Lowered Insulin Levels. [Baseline and 24 after hCG]

   17 hydroxyprogesterone levels

3. Anti-Mullerian Hormone (AMH) [Baseline]

Other Outcome Measures

1. Follicle Count on 3-D Ultrasound in PCOS Women and Normal Controls [baseline]

   3-D ultrasound was not assessed; instead 2-D ultrasound was performed

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 37 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

A group of 40 women with PCOS and 20 normal women ages 18-37 will be studied.

• Subjects will be determined to have PCOS based on clinical history of irregular menses and clinical or laboratory evidence of hyperandrogenism and polycystic ovaries on ultrasound.

• Subjects should not have been on any hormonal therapy or metformin for at least 2 months prior to study start.

• Subjects will be determined to be normal controls if they have a clinical history of regular periods

Exclusion Criteria:

• Women with hemoglobin less than 11 gm/dl at screening evaluation

• Women with untreated thyroid abnormalities

• Pregnant women or women who are nursing

• Women with BMI > 37

• Women with known sensitivity to the agents being used

• Women with prosthetic devices (i.e.,ear)/ shunts (ventricular), Hearing aids, Metal plate/pins/screws/wires

• Women with diabetes, or renal, liver, or heart disease.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCSD Medical Center	San Diego	California	United States	92103

Sponsors and Collaborators

• University of California, San Diego

Investigators

• Principal Investigator: R. Jeffrey Chang, M.D., Professor

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Jeffrey Chang, MD, Principal Investigator, University of California, San Diego
• ClinicalTrials.gov Identifier: NCT00989781
• Other Study ID Numbers: 090560
• First Posted: Oct 6, 2009
• Last Update Posted: Jun 4, 2018
• Last Verified: May 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Jeffrey Chang, MD, Principal Investigator, University of California, San Diego: PCOS, Androgens, ovary, polycystic
• Additional relevant MeSH terms: Polycystic Ovary Syndrome; Syndrome; Dexamethasone; Chorionic Gonadotropin; Hormones; Follicle Stimulating Hormone; Cosyntropin; Adrenocorticotropic Hormone; Melanocyte-Stimulating Hormones; beta-Endorphin

Study Results

Participant Flow

Recruitment Details	Subjects were recruited from UC San Dego clinics and by advertisement in the community. Recruitment began in the summer of 2011 and was completed in Septemebr 2013. Explanation of the research protocol was done by phone and in person.
Pre-assignment Detail	41 subjects recruited. 5 dropped out prior to study. Of 36 eligible for adrenal study, 8 dropped out before study,

Arm/Group Title	PCOS Women	Normal Women
Arm/Group Description	Each subject will undergo pelvic ultrasound followed by iv recombinant human chorionic gonadotropin (r-hCG) stimulation. 1 month later the r-hCG test will be repeated 24 hr after injection of recombinant human follicle stimulating hormone (FSH). After 1 month, subjects will receive a 7 hr dose-response infusion of adrenocorticotropin (ACTH) with blood sampling. Dexamethasone will be given prior to ACTH. After 1 month, subject will receive r-hCG as described above followed the next day by an oral glucose tolerance test (OGTT). Subsequently, subjects will take Diazoxide 3 times a day for 2 weeks. At weekly intervals (2 weeks), the r-hCG stimulation test will be repeated followed the next day by an OGTT.	Each subject will undergo pelvic ultrasound followed by iv recombinant human chorionic gonadotropin (r-hCG) stimulation. 1 month later the r-hCG test will be repeated 24 hr after an injection of recombinant human follicle stimulating hormone (FSH). After 1 month, subjects will receive a 7 hr dose-response infusion of adrenocorticotropin (ACTH) with blood sampling. Dexamethasone will be given prior to ACTH. After 1 month, subject will receive r-hCG as described above followed the next day by an oral glucose tolerance test (OGTT). Subsequently, subjects will take Diazoxide 3 times a day for 2 weeks. At weekly intervals (2 weeks), the r-hCG stimulation test will be repeated followed the next day by an OGTT.
Period Title: Ovarian Response to hCG
STARTED	21	20
COMPLETED	18	18
NOT COMPLETED	3	2
Period Title: Ovarian Response to hCG
STARTED	18	18
COMPLETED	13	15
NOT COMPLETED	5	3

Baseline Characteristics

Arm/Group Title	PCOS Women	Normal Women	Total
Arm/Group Description	Each subject will undergo pelvic 3D ultrasound followed by an iv recombinant human chorionic gonadotropin (r-hCG) stimulation test. One month later the r-hCG test will be repeated 24 hr after an injection of recombinant human follicle stimulating hormone (FSH). After 1 month, subjects will receive a 7 hr dose-response infusion of adrenocorticotropin (ACTH) with blood sampling. Dexamethasone will be given prior to ACTH. After 1 month, subject will receive r-hCG as described above followed the next day by an oral glucose tolerance test (OGTT). Subsequently, subjects will take Diazoxide 3 times a day for 2 weeks. At weekly intervals (2 weeks), the r-hCG stimulation test will be repeated followed the next day by an OGTT as described above.	Each subject will undergo pelvic 3D ultrasound followed by an iv recombinant human chorionic gonadotropin (r-hCG) stimulation test. One month later the r-hCG test will be repeated 24 hr after an injection of recombinant human follicle stimulating hormone (FSH). After 1 month, subjects will receive a 7 hr dose-response infusion of adrenocorticotropin (ACTH) with blood sampling. Dexamethasone will be given prior to ACTH. After 1 month, subject will receive r-hCG as described above followed the next day by an oral glucose tolerance test (OGTT). Subsequently, subjects will take Diazoxide 3 times a day for 2 weeks. At weekly intervals (2 weeks), the r-hCG stimulation test will be repeated followed the next day by an OGTT as described above.	Total of all reporting groups
Overall Participants	21	20	41
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	21 100%	20 100%	41 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	21 100%	20 100%	41 100%
Male	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	21 100%	20 100%	41 100%

Outcome Measures

1. Primary Outcome

Title	17-hydroxyprogesterone Responses to hCG in PCOS Women and Normal Controls
Description	Change from baseline in 17-hydroxyprogesterone at 24 hours after hCG injection
Time Frame	Baseline and 24 hours after hCG

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	NR-PCOS Women	HR-PCOS Women	Normal Women
Arm/Group Description	PCOS women with normal 17-OHP responses to hCG are designated as NR-PCOS. Each subject will undergo pelvic ultrasound followed by iv recombinant human chorionic gonadotropin (r-hCG) stimulation. 1 month later the r-hCG test will be repeated 24 hr after injection of recombinant human follicle stimulating hormone (FSH). After 1 month, subjects will receive a 7 hr dose-response infusion of adrenocorticotropin (ACTH) with blood sampling. Dexamethasone will be given prior to ACTH. After 1 month, subject will receive r-hCG as described above followed the next day by an oral glucose tolerance test (OGTT). Subsequently, subjects will take Diazoxide 3 times a day for 2 weeks. At weekly intervals (2 weeks), the r-hCG stimulation test will be repeated followed the next day by an OGTT.	PCOS women with exaggerated 17-OHP responses to hCG are designated as HR-PCOS. Each subject will undergo pelvic ultrasound followed by iv recombinant human chorionic gonadotropin (r-hCG) stimulation. 1 month later the r-hCG test will be repeated 24 hr after injection of recombinant human follicle stimulating hormone (FSH). After 1 month, subjects will receive a 7 hr dose-response infusion of adrenocorticotropin (ACTH) with blood sampling. Dexamethasone will be given prior to ACTH. After 1 month, subject will receive r-hCG as described above followed the next day by an oral glucose tolerance test (OGTT). Subsequently, subjects will take Diazoxide 3 times a day for 2 weeks. At weekly intervals (2 weeks), the r-hCG stimulation test will be repeated followed the next day by an OGTT.	Each subject will undergo pelvic ultrasound followed by iv recombinant human chorionic gonadotropin (r-hCG) stimulation. 1 month later the r-hCG test will be repeated 24 hr after an injection of recombinant human follicle stimulating hormone (FSH). After 1 month, subjects will receive a 7 hr dose-response infusion of adrenocorticotropin (ACTH) with blood sampling. Dexamethasone will be given prior to ACTH. After 1 month, subject will receive r-hCG as described above followed the next day by an oral glucose tolerance test (OGTT). Subsequently, subjects will take Diazoxide 3 times a day for 2 weeks. At weekly intervals (2 weeks), the r-hCG stimulation test will be repeated followed the next day by an OGTT.
Measure Participants	10	8	18
Mean (Standard Error) [ng/ml]	1.3 (0.2)	3 (1)	1.1 (0.2)

2. Secondary Outcome

Title	Adrenal 17-hydroxyprogesterone Response to ACTH in PCOS Women and Normal Controls
Description	17-hydroxyprogesterone response to ACTH infusion in women with PCOS and normal women. Response is reported as a single value generated by summing the data at end time frame.
Time Frame	Baseline and 1, 2, 3, 4, 5, and 6 hours after ACTH

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	NR-PCOS Women	HR-PCOS Women	Normal Women
Arm/Group Description	PCOS women with normal 17-OHP responses to hCG are designated as NR-PCOS. Each subject will undergo pelvic ultrasound followed by iv recombinant human chorionic gonadotropin (r-hCG) stimulation. 1 month later the r-hCG test will be repeated 24 hr after injection of recombinant human follicle stimulating hormone (FSH). After 1 month, subjects will receive a 7 hr dose-response infusion of adrenocorticotropin (ACTH) with blood sampling. Dexamethasone will be given prior to ACTH. After 1 month, subject will receive r-hCG as described above followed the next day by an oral glucose tolerance test (OGTT). Subsequently, subjects will take Diazoxide 3 times a day for 2 weeks. At weekly intervals (2 weeks), the r-hCG stimulation test will be repeated followed the next day by an OGTT.	PCOS women with exaggerated 17-OHP responses to hCG are designated as HR-PCOS. Each subject will undergo pelvic ultrasound followed by iv recombinant human chorionic gonadotropin (r-hCG) stimulation. 1 month later the r-hCG test will be repeated 24 hr after injection of recombinant human follicle stimulating hormone (FSH). After 1 month, subjects will receive a 7 hr dose-response infusion of adrenocorticotropin (ACTH) with blood sampling. Dexamethasone will be given prior to ACTH. After 1 month, subject will receive r-hCG as described above followed the next day by an oral glucose tolerance test (OGTT). Subsequently, subjects will take Diazoxide 3 times a day for 2 weeks. At weekly intervals (2 weeks), the r-hCG stimulation test will be repeated followed the next day by an OGTT.	Each subject will undergo pelvic ultrasound followed by iv recombinant human chorionic gonadotropin (r-hCG) stimulation. 1 month later the r-hCG test will be repeated 24 hr after an injection of recombinant human follicle stimulating hormone (FSH). After 1 month, subjects will receive a 7 hr dose-response infusion of adrenocorticotropin (ACTH) with blood sampling. Dexamethasone will be given prior to ACTH. After 1 month, subject will receive r-hCG as described above followed the next day by an oral glucose tolerance test (OGTT). Subsequently, subjects will take Diazoxide 3 times a day for 2 weeks. At weekly intervals (2 weeks), the r-hCG stimulation test will be repeated followed the next day by an OGTT.
Measure Participants	6	7	15
Mean (Standard Error) [ng/ml]	6.0 (0.8)	8.1 (0.4)	6.2 (0.4)

3. Secondary Outcome

Title	17 Hydroxyprogesterone Response to hCG Injection After Lowered Insulin Levels.
Description	17 hydroxyprogesterone levels
Time Frame	Baseline and 24 after hCG

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	NR-PCOS Women	HR-PCOS Women	Normal Women
Arm/Group Description	PCOS women with normal 17-OHP responses to hCG are designated as NR-PCOS. Each subject will undergo pelvic ultrasound followed by iv recombinant human chorionic gonadotropin (r-hCG) stimulation. 1 month later the r-hCG test will be repeated 24 hr after injection of recombinant human follicle stimulating hormone (FSH). After 1 month, subjects will receive a 7 hr dose-response infusion of adrenocorticotropin (ACTH) with blood sampling. Dexamethasone will be given prior to ACTH. After 1 month, subject will receive r-hCG as described above followed the next day by an oral glucose tolerance test (OGTT). Subsequently, subjects will take Diazoxide 3 times a day for 2 weeks. At weekly intervals (2 weeks), the r-hCG stimulation test will be repeated followed the next day by an OGTT.	PCOS women with exaggerated 17-OHP responses to hCG are designated as HR-PCOS. Each subject will undergo pelvic ultrasound followed by iv recombinant human chorionic gonadotropin (r-hCG) stimulation. 1 month later the r-hCG test will be repeated 24 hr after injection of recombinant human follicle stimulating hormone (FSH). After 1 month, subjects will receive a 7 hr dose-response infusion of adrenocorticotropin (ACTH) with blood sampling. Dexamethasone will be given prior to ACTH. After 1 month, subject will receive r-hCG as described above followed the next day by an oral glucose tolerance test (OGTT). Subsequently, subjects will take Diazoxide 3 times a day for 2 weeks. At weekly intervals (2 weeks), the r-hCG stimulation test will be repeated followed the next day by an OGTT.	Each subject will undergo pelvic ultrasound followed by iv recombinant human chorionic gonadotropin (r-hCG) stimulation. 1 month later the r-hCG test will be repeated 24 hr after an injection of recombinant human follicle stimulating hormone (FSH). After 1 month, subjects will receive a 7 hr dose-response infusion of adrenocorticotropin (ACTH) with blood sampling. Dexamethasone will be given prior to ACTH. After 1 month, subject will receive r-hCG as described above followed the next day by an oral glucose tolerance test (OGTT). Subsequently, subjects will take Diazoxide 3 times a day for 2 weeks. At weekly intervals (2 weeks), the r-hCG stimulation test will be repeated followed the next day by an OGTT.
Measure Participants	0	2	2
Count of Participants [Participants]	0 0%	0 0%	0 0%

4. Secondary Outcome

Title	Anti-Mullerian Hormone (AMH)
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	NR-PCOS Women	HR-PCOS Women	Normal Women
Arm/Group Description	PCOS women with normal 17-OHP responses to hCG are designated as NR-PCOS. Each subject will undergo pelvic ultrasound followed by iv recombinant human chorionic gonadotropin (r-hCG) stimulation. 1 month later the r-hCG test will be repeated 24 hr after injection of recombinant human follicle stimulating hormone (FSH). After 1 month, subjects will receive a 7 hr dose-response infusion of adrenocorticotropin (ACTH) with blood sampling. Dexamethasone will be given prior to ACTH. After 1 month, subject will receive r-hCG as described above followed the next day by an oral glucose tolerance test (OGTT). Subsequently, subjects will take Diazoxide 3 times a day for 2 weeks. At weekly intervals (2 weeks), the r-hCG stimulation test will be repeated followed the next day by an OGTT.	PCOS women with exaggerated 17-OHP responses to hCG are designated as HR-PCOS. Each subject will undergo pelvic ultrasound followed by iv recombinant human chorionic gonadotropin (r-hCG) stimulation. 1 month later the r-hCG test will be repeated 24 hr after injection of recombinant human follicle stimulating hormone (FSH). After 1 month, subjects will receive a 7 hr dose-response infusion of adrenocorticotropin (ACTH) with blood sampling. Dexamethasone will be given prior to ACTH. After 1 month, subject will receive r-hCG as described above followed the next day by an oral glucose tolerance test (OGTT). Subsequently, subjects will take Diazoxide 3 times a day for 2 weeks. At weekly intervals (2 weeks), the r-hCG stimulation test will be repeated followed the next day by an OGTT.	Each subject will undergo pelvic ultrasound followed by iv recombinant human chorionic gonadotropin (r-hCG) stimulation. 1 month later the r-hCG test will be repeated 24 hr after an injection of recombinant human follicle stimulating hormone (FSH). After 1 month, subjects will receive a 7 hr dose-response infusion of adrenocorticotropin (ACTH) with blood sampling. Dexamethasone will be given prior to ACTH. After 1 month, subject will receive r-hCG as described above followed the next day by an oral glucose tolerance test (OGTT). Subsequently, subjects will take Diazoxide 3 times a day for 2 weeks. At weekly intervals (2 weeks), the r-hCG stimulation test will be repeated followed the next day by an OGTT.
Measure Participants	10	8	18
Mean (Standard Error) [ng/ml]	16.0 (1.5)	6.7 (1.5)	5.3 (1.0)

5. Other Pre-specified Outcome

Title	Follicle Count on 3-D Ultrasound in PCOS Women and Normal Controls
Description	3-D ultrasound was not assessed; instead 2-D ultrasound was performed
Time Frame	baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	NR-PCOS Women	HR-PCOS Women	Normal Women
Arm/Group Description	PCOS women with normal 17-OHP responses to hCG are designated as NR-PCOS. Each subject will undergo pelvic ultrasound followed by iv recombinant human chorionic gonadotropin (r-hCG) stimulation. 1 month later the r-hCG test will be repeated 24 hr after injection of recombinant human follicle stimulating hormone (FSH). After 1 month, subjects will receive a 7 hr dose-response infusion of adrenocorticotropin (ACTH) with blood sampling. Dexamethasone will be given prior to ACTH. After 1 month, subject will receive r-hCG as described above followed the next day by an oral glucose tolerance test (OGTT). Subsequently, subjects will take Diazoxide 3 times a day for 2 weeks. At weekly intervals (2 weeks), the r-hCG stimulation test will be repeated followed the next day by an OGTT.	PCOS women with exaggerated 17-OHP responses to hCG are designated as HR-PCOS. Each subject will undergo pelvic ultrasound followed by iv recombinant human chorionic gonadotropin (r-hCG) stimulation. 1 month later the r-hCG test will be repeated 24 hr after injection of recombinant human follicle stimulating hormone (FSH). After 1 month, subjects will receive a 7 hr dose-response infusion of adrenocorticotropin (ACTH) with blood sampling. Dexamethasone will be given prior to ACTH. After 1 month, subject will receive r-hCG as described above followed the next day by an oral glucose tolerance test (OGTT). Subsequently, subjects will take Diazoxide 3 times a day for 2 weeks. At weekly intervals (2 weeks), the r-hCG stimulation test will be repeated followed the next day by an OGTT.	Each subject will undergo pelvic ultrasound followed by iv recombinant human chorionic gonadotropin (r-hCG) stimulation. 1 month later the r-hCG test will be repeated 24 hr after an injection of recombinant human follicle stimulating hormone (FSH). After 1 month, subjects will receive a 7 hr dose-response infusion of adrenocorticotropin (ACTH) with blood sampling. Dexamethasone will be given prior to ACTH. After 1 month, subject will receive r-hCG as described above followed the next day by an oral glucose tolerance test (OGTT). Subsequently, subjects will take Diazoxide 3 times a day for 2 weeks. At weekly intervals (2 weeks), the r-hCG stimulation test will be repeated followed the next day by an OGTT.
Measure Participants	10	8	18
Mean (Standard Error) [Antral Follicle Count]	64.4 (9.5)	49.3 (5.6)	31.8 (3.4)

Adverse Events

Time Frame	2 years
Arm/Group Title	PCOS Women		Normal Women
Arm/Group Description	Each subject will undergo pelvic 3D ultrasound and an iv recombinant human chorionic gonadotropin (r-hCG) stimulation test. One month later r-hCG test will be repeated 24 hr after injection of recombinant human follicle stimulating hormone (FSH). After 1 month, subjects will receive a 7 hr dose-response infusion of adrenocorticotropin (ACTH) with blood sampling. Dexamethasone will be given before ACTH. After 1 month, subject will receive r-hCG as described above followed the next day by an oral glucose tolerance test (OGTT). Subsequently, subjects will take Diazoxide 3 times a day for 2 weeks. At weekly intervals, the r-hCG stimulation test and OGTT will be repeated as described above. 3-D Ultrasound: One time pelvic ultrasound recombinant human chorionic gonadotropin: Recombinant human chorionic gonadotropin will be given iv and blood samples obtained before and 24 hr afterwards Recombinant human follicle stimulating		Each subject will undergo pelvic 3D ultrasound and an iv recombinant human chorionic gonadotropin (r-hCG) stimulation test. One month later the r-hCG test will be repeated 24 hr after an injection of recombinant human follicle stimulating hormone (FSH). After 1 month, subjects will receive a 7 hr dose-response infusion of adrenocorticotropin (ACTH) with blood sampling. Dexamethasone will be given prior to ACTH. After 1 month, subject will receive r-hCG as described above followed the next day by an oral glucose tolerance test (OGTT). Subsequently, subjects will take Diazoxide 3 times a day for 2 weeks. At weekly intervals, the r-hCG stimulation test and OGTT will be repeated as described above. 3-D Ultrasound: One time pelvic ultrasound recombinant human chorionic gonadotropin: Recombinant human chorionic gonadotropin will be given iv and blood samples obtained before and 24 hr afterwards Recombinant human follicle stimulati
All Cause Mortality
	PCOS Women		Normal Women
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	PCOS Women		Normal Women
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/21 (0%)		0/20 (0%)
Other (Not Including Serious) Adverse Events
	PCOS Women		Normal Women
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/21 (0%)		0/20 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.