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Mechanisms of Increased Androgen Production Among Women With Polycystic Ovary Syndrome

Mechanisms of Increased Androgen Production Among Women With Polycystic Ovary Syndrome

Status
Completed
Phases
NA
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT00989781
Enrollment
41
Registered
2009-10-06
Start date
2009-09-30
Completion date
2013-09-30
Last updated
2018-06-04

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Polycystic Ovary Syndrome

Keywords

PCOS, Androgens, ovary, polycystic

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

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.

Interventions

RADIATION3-D Ultrasound

One time pelvic ultrasound

Recombinant human chorionic gonadotropin will be given iv and blood samples obtained before and 24 hr afterwards

DRUGRecombinant human follicle stimulating hormone

Recombinant human follicle stimulating hormone will be given iv and blood samples obtained before and 24 hr later.

Each subject will receive a 7 hr dose-response infusion of Adrenocorticotropin.

DRUGDexamethasone

Dexamethasone will be given prior to ACTH infusion test.

DRUGGlucose

Each subject will undergo 3 oral glcuose tolerance tests.

Sponsors

University of California, San Diego
Lead SponsorOTHER

Study design

Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SCREENING
Masking
NONE

Eligibility

Sex/Gender
FEMALE
Age
18 Years to 37 Years
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.

Design outcomes

Primary

MeasureTime frameDescription
17-hydroxyprogesterone Responses to hCG in PCOS Women and Normal ControlsBaseline and 24 hours after hCGChange from baseline in 17-hydroxyprogesterone at 24 hours after hCG injection

Secondary

MeasureTime frameDescription
Anti-Mullerian Hormone (AMH)Baseline
Adrenal 17-hydroxyprogesterone Response to ACTH in PCOS Women and Normal ControlsBaseline and 1, 2, 3, 4, 5, and 6 hours after ACTH17-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.
17 Hydroxyprogesterone Response to hCG Injection After Lowered Insulin Levels.Baseline and 24 after hCG17 hydroxyprogesterone levels

Other

MeasureTime frameDescription
Follicle Count on 3-D Ultrasound in PCOS Women and Normal Controlsbaseline3-D ultrasound was not assessed; instead 2-D ultrasound was performed

Countries

United States

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 details

41 subjects recruited. 5 dropped out prior to study. Of 36 eligible for adrenal study, 8 dropped out before study,

Participants by arm

ArmCount
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.
21
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.
20
Total41

Withdrawals & dropouts

PeriodReasonFG000FG001
Ovarian Response to hCGLost to Follow-up32

Baseline characteristics

CharacteristicPCOS WomenNormal WomenTotal
Age, Categorical
<=18 years
0 Participants0 Participants0 Participants
Age, Categorical
>=65 years
0 Participants0 Participants0 Participants
Age, Categorical
Between 18 and 65 years
21 Participants20 Participants41 Participants
Region of Enrollment
United States
21 participants20 participants41 participants
Sex: Female, Male
Female
21 Participants20 Participants41 Participants
Sex: Female, Male
Male
0 Participants0 Participants0 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
deaths
Total, all-cause mortality
— / —— / —
other
Total, other adverse events
0 / 210 / 20
serious
Total, serious adverse events
0 / 210 / 20

Outcome results

Primary

17-hydroxyprogesterone Responses to hCG in PCOS Women and Normal Controls

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

Time frame: Baseline and 24 hours after hCG

ArmMeasureValue (MEAN)Dispersion
NR-PCOS Women17-hydroxyprogesterone Responses to hCG in PCOS Women and Normal Controls1.3 ng/mlStandard Error 0.2
HR-PCOS Women17-hydroxyprogesterone Responses to hCG in PCOS Women and Normal Controls3 ng/mlStandard Error 1
Normal Women17-hydroxyprogesterone Responses to hCG in PCOS Women and Normal Controls1.1 ng/mlStandard Error 0.2
Secondary

17 Hydroxyprogesterone Response to hCG Injection After Lowered Insulin Levels.

17 hydroxyprogesterone levels

Time frame: Baseline and 24 after hCG

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
NR-PCOS Women17 Hydroxyprogesterone Response to hCG Injection After Lowered Insulin Levels.0 Participants
HR-PCOS Women17 Hydroxyprogesterone Response to hCG Injection After Lowered Insulin Levels.0 Participants
Normal Women17 Hydroxyprogesterone Response to hCG Injection After Lowered Insulin Levels.0 Participants
Secondary

Adrenal 17-hydroxyprogesterone Response to ACTH in PCOS Women and Normal Controls

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

ArmMeasureValue (MEAN)Dispersion
NR-PCOS WomenAdrenal 17-hydroxyprogesterone Response to ACTH in PCOS Women and Normal Controls6.0 ng/mlStandard Error 0.8
HR-PCOS WomenAdrenal 17-hydroxyprogesterone Response to ACTH in PCOS Women and Normal Controls8.1 ng/mlStandard Error 0.4
Normal WomenAdrenal 17-hydroxyprogesterone Response to ACTH in PCOS Women and Normal Controls6.2 ng/mlStandard Error 0.4
Secondary

Anti-Mullerian Hormone (AMH)

Time frame: Baseline

ArmMeasureValue (MEAN)Dispersion
NR-PCOS WomenAnti-Mullerian Hormone (AMH)16.0 ng/mlStandard Error 1.5
HR-PCOS WomenAnti-Mullerian Hormone (AMH)6.7 ng/mlStandard Error 1.5
Normal WomenAnti-Mullerian Hormone (AMH)5.3 ng/mlStandard Error 1
Other Pre-specified

Follicle Count on 3-D Ultrasound in PCOS Women and Normal Controls

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

Time frame: baseline

ArmMeasureValue (MEAN)Dispersion
NR-PCOS WomenFollicle Count on 3-D Ultrasound in PCOS Women and Normal Controls64.4 Antral Follicle CountStandard Error 9.5
HR-PCOS WomenFollicle Count on 3-D Ultrasound in PCOS Women and Normal Controls49.3 Antral Follicle CountStandard Error 5.6
Normal WomenFollicle Count on 3-D Ultrasound in PCOS Women and Normal Controls31.8 Antral Follicle CountStandard Error 3.4

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026