Mechanisms of Increased Androgen Production Among Women With Polycystic Ovary Syndrome

Polycystic Ovary Syndrome Clinical Trial

Official title:

Mechanisms of Increased Androgen Production Among Women With Polycystic Ovary Syndrome

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00989781
• Other study ID #: 090560
• Status: Completed
• Phase: N/A
• Start date: September 2009
• Est. completion date: September 2013

Study information

• Verified date: May 2018
• Source: University of California, San Diego
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 41
• Est. completion date: September 2013
• Est. primary completion date: September 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 37 Years

Eligibility

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.

Related Conditions & MeSH terms

• Polycystic Ovary Syndrome
• Syndrome

Intervention

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
• Recombinant human follicle stimulating hormone
Recombinant human follicle stimulating hormone will be given iv and blood samples obtained before and 24 hr later.
• Adrenocorticotropin
Each subject will receive a 7 hr dose-response infusion of Adrenocorticotropin.
• Dexamethasone
Dexamethasone will be given prior to ACTH infusion test.
• Glucose
Each subject will undergo 3 oral glcuose tolerance tests.

Locations

Country	Name	City	State
United States	UCSD Medical Center	San Diego	California

Sponsors (1)

Lead Sponsor	Collaborator
University of California, San Diego

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Follicle Count on 3-D Ultrasound in PCOS Women and Normal Controls	3-D ultrasound was not assessed; instead 2-D ultrasound was performed	baseline
Primary	17-hydroxyprogesterone Responses to hCG in PCOS Women and Normal Controls	Change from baseline in 17-hydroxyprogesterone at 24 hours after hCG injection	Baseline and 24 hours after hCG
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.	Baseline and 1, 2, 3, 4, 5, and 6 hours after ACTH
Secondary	17 Hydroxyprogesterone Response to hCG Injection After Lowered Insulin Levels.	17 hydroxyprogesterone levels	Baseline and 24 after hCG
Secondary	Anti-Mullerian Hormone (AMH)		Baseline