Symptoms and General Pathology

All Conditions

Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Syndrome

Polycystic Ovary Syndrome

Cysts

Ovarian Cysts

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Gonadal Disorders

Endocrine System Diseases

Anti-Inflammatory Agents

Antineoplastic Agents

Antiemetics

Gastrointestinal Agents

All Drugs and Chemicals

Antihypertensive Agents

Vasodilator Agents

Reproductive Control Agents

Dexamethasone

Androgens

Hormones

Follicle Stimulating Hormone

Dexamethasone acetate

Diazoxide

Cosyntropin

Chorionic Gonadotropin

Adrenocorticotropic Hormone

Melanocyte-Stimulating Hormones

beta-Endorphin

Endorphins

Glucocorticoids

Hormone Antagonists

Antineoplastic Agents, Hormonal

Neurotransmitter Agents

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.

3-D Ultrasound

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

recombinant human chorionic gonadotropin

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

Recombinant human follicle stimulating hormone

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

Adrenocorticotropin

Dexamethasone will be given prior to ACTH infusion test.

Each subject will undergo 3 oral glcuose tolerance tests.

Glucose

R. Jeffrey Chang, M.D.

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

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.

Mechanisms of Increased Androgen Production Among Women With Polycystic Ovary Syndrome

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

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

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.

University of California, San Diego

Principal Investigator

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

PCOS Women

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

Normal Women

Total

Age, Categorical

Sex: Female, Male

United States

Region of Enrollment

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.

NR-PCOS Women

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.

HR-PCOS Women

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.

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

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

17 Hydroxyprogesterone Response to hCG Injection After Lowered Insulin Levels.

Anti-Mullerian Hormone (AMH)

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

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.

Ovarian Response to hCG

Adrenal Response ot ACTH

Skin and Connective Tissue Diseases

Breast Neoplasms

Breast Diseases

Skin Diseases

Patients receive recombinant human chorionic gonadotropin subcutaneously three times weekly. Treatment continues weekly for 90 days in the absence of unacceptable toxicity.

microarray analysis

immunohistochemistry staining method

laboratory biomarker analysis

needle biopsy

Jose Russo, MD, FCAP

RATIONALE: Chemoprevention is the use of certain drugs to keep cancer from forming. The use of recombinant human chorionic gonadotropin may prevent breast cancer in premenopausal women with BRCA1 mutations.

PURPOSE: This clinical trial is studying recombinant human chorionic gonadotropin in preventing breast cancer in premenopausal women with BRCA1 mutations.

OBJECTIVES:

Primary

* Determine whether the genomic profiles of breast epithelial cells of high-breast cancer-risk women, as defined by their positive BRCA1 status and nulliparous condition, express a signature indicative of high-risk.

Secondary

* Determine whether women identified to express a "high-breast cancer-risk" signature will revert it to a "low-risk" signature after a 90-day treatment with r-hCG, which should have induced breast differentiation and genomic changes that would serve as biomarkers indicative of decreased breast cancer risk.

OUTLINE: Patients receive recombinant human chorionic gonadotropin subcutaneously three times weekly. Treatment continues weekly for 90 days in the absence of unacceptable toxicity.

Benign breast tissue specimens are collected by core needle biopsy at baseline, day 90, and day 270. Tissue samples are analyzed by cytopathology for epithelial normality, Ki67 immunohistochemical staining for cell proliferation, cDNA microarray for gene expression, and serum studies for hormone levels and biomarker determinations.

After completion of study treatment, patients are followed for 24 weeks.

Recombinant Human Chorionic Gonadotropin in Preventing Breast Cancer in Premenopausal Women With BRCA1 Mutations

Genomic Markers of Breast Cancer Prevention Induced by HCG in Women at High Risk

National Cancer Institute (NCI)

Fox Chase Cancer Center

Patients receive recombinant human chorionic gonadotropin subcutaneously three times weekly. Treatment continues weekly for 90 days in the absence of unacceptable toxicity.

recombinant human chorionic gonadotropin

microarray analysis

immunohistochemistry staining method

laboratory biomarker analysis

needle biopsy

Recombinant Human Chorionic Gonadotropin

Austria

Dr. Jose Russo

Measurement of Gene Expression in Breast Epithelial Cells Obtained for Asymptomatic High Breast Cancer Risk Nulliparous Premenopausal Women at Baseline, After Treatment With r-hCG at 90 Days, and at 270 Days From Baseline

Overall Study

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Mechanisms of Increased Androgen Production Among Women With Polycystic Ovary Syndrome	NCT00989781	Polycystic Ovar...	3-D Ultrasound recombinant hum... Recombinant hum... Adrenocorticotr... Dexamethasone Glucose	18 Years - 37 Years	University of California, San Diego
Mechanisms of Increased Androgen Production Among Women With Polycystic Ovary Syndrome	NCT00989781	Polycystic Ovar...	3-D Ultrasound recombinant hum... Recombinant hum... Adrenocorticotr... Dexamethasone Glucose	18 Years - 37 Years	University of California, San Diego
Recombinant Human Chorionic Gonadotropin in Preventing Breast Cancer in Premenopausal Women With BRCA1 Mutations	NCT00700778	BRCA1 Mutation Breast Cancer	recombinant hum... microarray anal... immunohistochem... laboratory biom... needle biopsy	20 Years - 40 Years	Fox Chase Cancer Center
Recombinant Human Chorionic Gonadotropin in Preventing Breast Cancer in Premenopausal Women With BRCA1 Mutations	NCT00700778	BRCA1 Mutation Breast Cancer	recombinant hum... microarray anal... immunohistochem... laboratory biom... needle biopsy	20 Years - 40 Years	Fox Chase Cancer Center
Mechanisms of Increased Androgen Production Among Women With Polycystic Ovary Syndrome	NCT00989781	Polycystic Ovar...	3-D Ultrasound recombinant hum... Recombinant hum... Adrenocorticotr... Dexamethasone Glucose	18 Years - 37 Years	University of California, San Diego
Mechanisms of Increased Androgen Production Among Women With Polycystic Ovary Syndrome	NCT00989781	Polycystic Ovar...	3-D Ultrasound recombinant hum... Recombinant hum... Adrenocorticotr... Dexamethasone Glucose	18 Years - 37 Years	University of California, San Diego

Spots Global Cancer Trial Database for recombinant human chorionic gonadotropin