Theca Cell Function in Women With Polycystic Ovary Syndrome (PCOS) - Full Text View

Purpose

The mechanism for increased androgen production in women with polycystic ovary syndrome (PCOS) is not well understood. Excess androgen production by the ovary is stimulated by increased pituitary luteinizing hormone (LH) secretion in this disorder. The investigators hypothesize that in PCOS women ovarian theca cells, which are responsible for androgen synthesis, are more sensitive to LH stimulation compared to that of theca cells from normal women. To test this hypothesis, the investigators propose to conduct a dose-response study in which androgen responses to multiple doses of human chorionic gonadotgropin (hCG), an LH surrogate, will be assessed in PCOS and normal women.

Condition	Intervention	Phase
Polycystic Ovary Syndrome	Drug: recombinant human chorionic gonadotropin	Phase 3


Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Diagnostic
Official Title:	Theca Cell Function in Women With Polycystic Ovary Syndrome

Resource links provided by NLM:

MedlinePlus related topics: Polycystic Ovary Syndrome

Drug Information available for: Chorionic Gonadotropin Choriogonadotropin Alfa

U.S. FDA Resources

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

Primary Outcome Measures:

Serum 17OHP Responses to hCG [ Time Frame: 24 hrs post dose ] [ Designated as safety issue: No ]
Assess serum 17OHP levels following each dose of hCG adminstration in PCOS and normal subjects

Secondary Outcome Measures:

Serum Testosterone Responses to hCG [ Time Frame: -0.5, 0, 0.5, 24 hrs ] [ Designated as safety issue: No ]


Enrollment:	25
Study Start Date:	September 2007
Study Completion Date:	September 2010
Primary Completion Date:	April 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: PCOS group Each subject will receive a dose (1, 10, 25, 100, or 250 micrograms) of recombinant human chorionic gonadotropin administered iv on 5 separate occasions.	Drug: recombinant human chorionic gonadotropin Each subject will receive a dose (1, 10, 25, 100, or 250 micrograms) of human chorionic gonadotropin administered intravenously on 5 separate occasions. Other Name: Ovidrel
Active Comparator: Control group Each subject will receive a dose (1, 10, 25, 100, or 250 micrograms) of recombinant human chorionic gonadotropin administered iv on 5 separate occasions.	Drug: recombinant human chorionic gonadotropin Each subject will receive a dose (1, 10, 25, 100, or 250 micrograms) of human chorionic gonadotropin administered intravenously on 5 separate occasions. Other Name: Ovidrel

Detailed Description:

Each subject (normal and PCOS women) will be admitted to the UCSD General Clinical Research Center (GCRC) for study on 5 occasions. All subjects will receive an intravenous injection of hCG dose of 1, 10, 25, 100, and 250 micrograms, each of which will be given on one of 5 different days each separated by at least two weeks at 8 AM. Blood samples will be obtained at t -0.5, 0, 0.5,and 24 hours after injection. All visits to the GCRC will be done as out patients. The total amount of blood withdrawn will be about 35 teaspoons. For normal control subjects this will be over a period of about 4-6 months and for PCOS subjects this will be over a period of about 6-10 weeks.

Eligibility


Ages Eligible for Study:	18 Years to 35 Years (Adult)
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

Normal CBC (Hemoglobin must be at least 11mg/dl)
Normal renal and liver function tests
Normal vital signs including normal blood pressure

Exclusion Criteria:

No oral contraceptives
No insulin lowering drugs
No anti-androgens (i.e., spironolactone, flutamide, finasteride, etc)
No medications that will influence androgen metabolism or clearance
No medications that will inhibit the cytochrome P450 enzyme system (cimetidine, ketoconozole, etc)
No use of clomiphene citrate within 3 months prior to study

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: NCT00747617

Locations


United States, California
University of California, San Diego, School of Medicine
La Jolla, California, United States, 92093

Sponsors and Collaborators

University of California, San Diego

Investigators


Principal Investigator:	R, Jeffrey Chang, M.D.	UCSD SChool of Medicine

More Information

Publications:

Chang RJ. The reproductive phenotype in polycystic ovary syndrome. Nat Clin Pract Endocrinol Metab. 2007 Oct;3(10):688-95. Review.

Wachs DS, Coffler MS, Malcom PJ, Shimasaki S, Chang RJ. Increased androgen response to follicle-stimulating hormone administration in women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2008 May;93(5):1827-33. doi: 10.1210/jc.2007-2664. Epub 2008 Feb 19.

Wachs DS, Coffler MS, Malcom PJ, Chang RJ. Comparison of follicle-stimulating-hormone-stimulated dimeric inhibin and estradiol responses as indicators of granulosa cell function in polycystic ovary syndrome and normal women. J Clin Endocrinol Metab. 2006 Aug;91(8):2920-5. Epub 2006 May 23.

Mehta RV, Malcom PJ, Chang RJ. The effect of androgen blockade on granulosa cell estradiol production after follicle-stimulating hormone stimulation in women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2006 Sep;91(9):3503-6. Epub 2006 Jun 27.

Mehta RV, Patel KS, Coffler MS, Dahan MH, Yoo RY, Archer JS, Malcom PJ, Chang RJ. Luteinizing hormone secretion is not influenced by insulin infusion in women with polycystic ovary syndrome despite improved insulin sensitivity during pioglitazone treatment. J Clin Endocrinol Metab. 2005 Apr;90(4):2136-41. Epub 2005 Jan 11.

Chang RJ. A practical approach to the diagnosis of polycystic ovary syndrome. Am J Obstet Gynecol. 2004 Sep;191(3):713-7. Review.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Maas KH, Chuan SS, Cook-Andersen H, Su HI, Duleba A, Chang RJ. Relationship between 17-hydroxyprogesterone responses to human chorionic gonadotropin and markers of ovarian follicle morphology in women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2015 Jan;100(1):293-300. doi: 10.1210/jc.2014-2956.

Cook-Andersen H, Chuan SS, Maas K, Rosencrantz MA, Su HI, Lawson M, Mason HD, Chang RJ. Lack of Serum anti-Mullerian hormone responses after recombinant human chorionic gonadotropin stimulation in women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2015 Jan;100(1):251-7. doi: 10.1210/jc.2014-2948.

Rosencrantz MA, Coffler MS, Haggan A, Duke KB, Donohue MC, Shayya RF, Su HI, Chang RJ. Clinical evidence for predominance of delta-5 steroid production in women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2011 Apr;96(4):1106-13. doi: 10.1210/jc.2010-2200. Epub 2011 Jan 26.


Responsible Party:	Jeffrey Chang, MD, Principal investigator, University of California, San Diego
ClinicalTrials.gov Identifier:	NCT00747617 History of Changes
Other Study ID Numbers:	060679
Study First Received:	September 4, 2008
Results First Received:	August 4, 2011
Last Updated:	February 9, 2016
Health Authority:	United States: Food and Drug Administration
Individual Participant Data
Plan to Share IPD:	No

Keywords provided by University of California, San Diego:


polycystic ovary syndrome androgens ovary LH

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 Chorionic Gonadotropin Reproductive Control Agents Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 30, 2016