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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.
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, 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 The total amount of blood withdrawn will be about 35 teaspoons.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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Serum 17OHP Responses to hCG | Assess serum 17OHP levels following each dose of hCG adminstration in PCOS and normal subjects | 24 hrs post dose |
| Measure | Description | Time Frame |
|---|---|---|
| Serum Testosterone Responses to hCG | Mean serum testosterone levels before and after hCG injection. Serum testosterone levels before (-0.5 and 0 hrs) were averaged to achieve a single value | -0.5, 0, 24 hrs |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| R, Jeffrey Chang, M.D. | UCSD SChool of Medicine | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of California, San Diego, School of Medicine | La Jolla | California | 92093 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 17893687 | Background | Chang RJ. The reproductive phenotype in polycystic ovary syndrome. Nat Clin Pract Endocrinol Metab. 2007 Oct;3(10):688-95. doi: 10.1038/ncpendmet0637. | |
| 18285408 | 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. |
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Subjects involved women with PCOS and normal control women undergoing hCG stimulation
Subjects recruited from UCSD clinics and coal advertising beginning in 2009 and ending in 2010
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| ID | Title | Description |
|---|---|---|
| FG000 | PCOS | Each subject will receive a dose (1, 10, 25, 100, or 250 micrograms) of hCG administered intravenously on 5 separate occasions. |
| FG001 | Normal | Each subject will receive a dose (1, 10, 25, 100, or 250 micrograms) of hCG administered intravenously on 5 separate occasions. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | PCOS | Each subject will receive a dose (1, 10, 25, 100, or 250 micrograms) of hCG administered intravenously on 5 separate occasions. |
| BG001 | Normal | Each subject will receive a dose (1, 10, 25, 100, or 250 micrograms) of hCG administered intravenously on 5 separate occasions. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Serum 17OHP Responses to hCG | Assess serum 17OHP levels following each dose of hCG adminstration in PCOS and normal subjects | PCOS and Normal groups were analyzed according to peak 17OHP levels at each dose of r-hCG. | Posted | Mean | Standard Error | ng/ml | 24 hrs post dose |
|
2 years
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | PCOS | Each subject will receive a dose (1, 10, 25, 100, or 250 micrograms) of hCG administered intravenously on 5 separate occasions. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| R. Jeffrey Chang, M.D. | UCSD School of Medicine | 858-534-8930 | rjchang@ucsd.edu |
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| ID | Term |
|---|---|
| D011085 | Polycystic Ovary Syndrome |
| ID | Term |
|---|---|
| D010048 | Ovarian Cysts |
| D003560 | Cysts |
| D009369 | Neoplasms |
| D010049 | Ovarian Diseases |
| D000291 |
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| ID | Term |
|---|---|
| D006063 | Chorionic Gonadotropin |
| C412828 | Ovidrel |
| ID | Term |
|---|---|
| D006062 | Gonadotropins |
| D036361 | Peptide Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
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|
| 16720653 | 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. |
| 16804036 | 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. |
| 15644405 | 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. |
| 15467530 | 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. |
| 27473350 | Derived | 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. |
| 25313914 | 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. |
| 25303490 | 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. |
| 24188875 | 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. |
| 21270326 | 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. |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Units | Counts |
|---|---|
| Participants |
|
|
|
| Secondary | Serum Testosterone Responses to hCG | Mean serum testosterone levels before and after hCG injection. Serum testosterone levels before (-0.5 and 0 hrs) were averaged to achieve a single value | Posted | Mean | Standard Error | ng/ml | -0.5, 0, 24 hrs |
|
|
|
| 0 |
| 13 |
| 0 |
| 13 |
| 0 |
| 13 |
| EG001 | Normal | Each subject will receive a dose (1, 10, 25, 100, or 250 micrograms) of hCG administered intravenously on 5 separate occasions. | 0 | 12 | 0 | 12 | 0 | 12 |
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| Adnexal Diseases |
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D000091662 | Genital Diseases |
| D006058 | Gonadal Disorders |
| D004700 | Endocrine System Diseases |
| D010926 | Placental Hormones |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D011257 | Pregnancy Proteins |
| D011506 | Proteins |