Theca Cell Function in Women With Polycystic Ovary Syndrome (PCOS)

NCT00747617 | Completed Phase 3 Results DMC

• 1 other identifier: 060679
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Polycystic Ovary Syndrome

Keywords

polycystic ovary syndrome; androgens; ovary; LH

Outcome Measures

Primary Outcomes (1)

• Serum 17OHP Responses to hCG

  Assess serum 17OHP levels following each dose of hCG adminstration in PCOS and normal subjects

  24 hrs post dose

Secondary Outcomes (1)

• Serum Testosterone Responses to hCG

  -0.5, 0, 24 hrs

Study Arms (2)

PCOS group

ACTIVE COMPARATOR

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

Control group

ACTIVE COMPARATOR

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

Interventions

recombinant human chorionic gonadotropin DRUG

Each subject will receive a dose (1, 10, 25, 100, or 250 micrograms) of human chorionic gonadotropin administered intravenously on 5 separate occasions.

Also known as: Ovidrel

Control group; PCOS group

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of California, San Diego: lead

Study Sites (1)

University of California, San Diego, School of Medicine

La Jolla, California, 92093, United States

Location

Related Publications (11)

• Chang RJ. The reproductive phenotype in polycystic ovary syndrome. Nat Clin Pract Endocrinol Metab. 2007 Oct;3(10):688-95. doi: 10.1038/ncpendmet0637.

  PMID: 17893687 BACKGROUND

• 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.

  PMID: 18285408 BACKGROUND

• 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. doi: 10.1210/jc.2006-0442. Epub 2006 May 23.

  PMID: 16720653 BACKGROUND

• 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. doi: 10.1210/jc.2006-0752. Epub 2006 Jun 27.

  PMID: 16804036 BACKGROUND

• 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. doi: 10.1210/jc.2004-1040. Epub 2005 Jan 11.

  PMID: 15644405 BACKGROUND

• Chang RJ. A practical approach to the diagnosis of polycystic ovary syndrome. Am J Obstet Gynecol. 2004 Sep;191(3):713-7. doi: 10.1016/j.ajog.2004.04.045.

  PMID: 15467530 BACKGROUND

• Maas KH, Chuan S, Harrison E, Cook-Andersen H, Duleba AJ, Chang RJ. Androgen responses to adrenocorticotropic hormone infusion among individual women with polycystic ovary syndrome. Fertil Steril. 2016 Oct;106(5):1252-1257. doi: 10.1016/j.fertnstert.2016.06.039. Epub 2016 Jul 26.

  PMID: 27473350 DERIVED

• 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.

  PMID: 25313914 DERIVED

• 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.

  PMID: 25303490 DERIVED

• Shayya RF, Rosencrantz MA, Chuan SS, Cook-Andersen H, Roudebush WE, Irene Su H, Shimasaki S, Chang RJ. Decreased inhibin B responses following recombinant human chorionic gonadotropin administration in normal women and women with polycystic ovary syndrome. Fertil Steril. 2014 Jan;101(1):275-9. doi: 10.1016/j.fertnstert.2013.09.037. Epub 2013 Nov 1.

  PMID: 24188875 DERIVED

• 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.

  PMID: 21270326 DERIVED

MeSH Terms

Conditions

Polycystic Ovary Syndrome

Interventions

Chorionic Gonadotropin; Ovidrel

Condition Hierarchy (Ancestors)

Ovarian Cysts; Cysts; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Gonadal Disorders; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Gonadotropins; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Placental Hormones; Peptides; Amino Acids, Peptides, and Proteins; Pregnancy Proteins; Proteins

Results Point of Contact

• Title: R. Jeffrey Chang, M.D.
• Organization: UCSD School of Medicine

rjchang@ucsd.edu

858-534-8930

Study Officials

• R, Jeffrey Chang, M.D.

  UCSD SChool of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator

Study Record Dates

• First Submitted: September 4, 2008
• First Posted: September 5, 2008
• Study Start: September 1, 2007
• Primary Completion: April 1, 2010
• Study Completion: September 1, 2010
• Last Updated: November 21, 2018
• Results First Posted: January 29, 2013

Record last verified: 2018-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)