Mechanisms of Increased Androgen Production Among Women With Polycystic Ovary Syndrome

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2013 by University of California, San Diego
Sponsor:
Information provided by (Responsible Party):
Jeffrey Chang, MD, University of California, San Diego
ClinicalTrials.gov Identifier:
NCT00989781
First received: October 5, 2009
Last updated: January 14, 2013
Last verified: January 2013
  Purpose

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 Intervention
Polycystic Ovary Syndrome
Radiation: 3-D Ultrasound
Drug: recombinant human chorionic gonadotropin
Drug: Recombinant follicle stimulating hormone
Drug: Dexamethasone
Drug: Adrenocorticotropin
Drug: Glucose

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Mechanisms of Increased Androgen Production Among Women With Polycystic Ovary Syndrome

Resource links provided by NLM:


Further study details as provided by University of California, San Diego:

Primary Outcome Measures:
  • 17-hydroxyprogesterone responses to hCG with and without FSH in PCOS women and normal controls [ Time Frame: up to 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Follicle count on 3-D Ultrasound in PCOS women and normal controls [ Time Frame: up to 2 years ] [ Designated as safety issue: No ]
  • Adrenal androgen response to ACTH in PCOS women and normal controls [ Time Frame: up to 2 years ] [ Designated as safety issue: No ]
  • 17-hydroxyprogesterone response to hCG in the setting of reduced insulin secretion in PCOS women [ Time Frame: 09/2013 ] [ Designated as safety issue: No ]

Estimated Enrollment: 60
Study Start Date: September 2009
Estimated Study Completion Date: September 2013
Estimated Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 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: Dexamethasone
Dexamethasone will be given prior to ACTH infusion test.
Drug: Adrenocorticotropin
Each subject will receive a 7 hr dose-response infusion of adrenocorticotropin (ACTH.
Other Names:
  • Cosyntropin
  • ACTH
Drug: Glucose
Each subject will undergo 3 oral glcuose tolerance tests.
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 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: Dexamethasone
Dexamethasone will be given prior to ACTH infusion test.
Drug: Adrenocorticotropin
Each subject will receive a 7 hr dose-response infusion of adrenocorticotropin (ACTH.
Other Names:
  • Cosyntropin
  • ACTH
Drug: Glucose
Each subject will undergo 3 oral glcuose tolerance tests.

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.

  Eligibility

Ages Eligible for Study:   18 Years to 37 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00989781

Contacts
Contact: Kevin Maas, M.D., Ph.D. 858-534-8930 khmaas2@gmail.com
Contact: R. Jeffrey Chang, M.D. 858-534-8930 rjchang@ucsd.edu

Locations
United States, California
UCSD Medical Center Recruiting
San Diego, California, United States, 92103
Contact: Kevin Maas, M.D., Ph.D.    858-534-8930    khmaas2@gmail.com   
Contact: R. Jeffrey Chang, M.D.    858-534-8930    rjchang@ucsd.edu   
Principal Investigator: R. Jeffrey Chang, M.D.         
Sponsors and Collaborators
University of California, San Diego
Investigators
Principal Investigator: R. Jeffrey Chang, M.D. Professor
  More Information

No publications provided

Responsible Party: Jeffrey Chang, MD, Principal Investigator, University of California, San Diego
ClinicalTrials.gov Identifier: NCT00989781     History of Changes
Other Study ID Numbers: 090560
Study First Received: October 5, 2009
Last Updated: January 14, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by University of California, San Diego:
PCOS, Androgens, ovary, polycystic

Additional relevant MeSH terms:
Syndrome
Polycystic Ovary Syndrome
Disease
Pathologic Processes
Ovarian Cysts
Cysts
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Gonadal Disorders
Endocrine System Diseases
Hormones
Dexamethasone
Dexamethasone 21-phosphate
Follicle Stimulating Hormone
Adrenocorticotropic Hormone
Dexamethasone acetate
BB 1101
Androgens
Chorionic Gonadotropin
Beta-Endorphin
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents

ClinicalTrials.gov processed this record on October 16, 2014