Etiological Factors of Obesity-Associated Hyperandrogenemia in Peripubertal Girls (CRM002)
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|ClinicalTrials.gov Identifier: NCT00928759|
Recruitment Status : Recruiting
First Posted : June 26, 2009
Last Update Posted : October 11, 2019
|Condition or disease|
|Obesity Hyperandrogenemia Polycystic Ovary Syndrome|
A number of pathophysiological mechanisms underlie the polycystic ovary syndrome (PCOS). Neuroendocrine abnormalities play a significant role in most women with PCOS, and PCOS is associated with relative resistance of the gonadotropin releasing hormone (GnRH) pulse generator to negative feedback by progesterone and estradiol. This hypothalamic resistance to negative feedback appears to be a result of hyperandrogenemia (HA), and can also occur in adolescents with HA. We have hypothesized that peripubertal HA (which can represent a forerunner of adult PCOS) can promote the development of PCOS in part via induction of hypothalamic resistance to negative feedback. However, the cause of peripubertal HA remains largely unknown. Obesity is a well-recognized pathophysiological factor in the HA of adult PCOS; and recent data demonstrate that peripubertal obesity is associated with HA. However, the mechanisms underlying the relationship between peripubertal obesity and HA—and the marked variability of androgen levels observed among obese girls—are unknown. We have gathered preliminary data that suggests that obese pre- and early pubertal girls with high androgen levels also exhibit greater degrees of insulin resistance compared to obese girls with lower androgens.
The primary goal of this pilot project is to begin to establish the relationship between insulin resistance (as determined by insulin clamp studies) and free testosterone concentrations in obese peripubertal girls. Secondarily, the aim is to assess the contributions of elevated luteinizing hormone (determined by frequent blood sampling for LH) in obesity-associated HA across puberty.
Subjects will be admitted to the General Clinical Research Center at 1600 h after 4 hours of fasting. We will measure luteinizing hormone every 10 minutes from 1800 h to 0900 h; other hormones (e.g., testosterone) will be assessed as well. Measurements of insulin and glucose will occur before and after a standardized mixed meal (eaten at 1900 h) and while fasting the following morning. A standard hyperinsulinemic euglycemic clamp procedure will be performed from 0900-1100 h.
Characterization of the factors underlying peripubertal HA may permit prediction of which pre- and early pubertal girls will subsequently go on to develop symptoms of PCOS. Data generated by this project will prompt novel future studies to investigate the complex interactions among metabolic and classical endocrine pathways that lead to PCOS.
|Study Type :||Observational|
|Estimated Enrollment :||40 participants|
|Official Title:||Etiological Factors of Obesity-Associated Hyperandrogenemia in Peripubertal Girls|
|Study Start Date :||March 2008|
|Estimated Primary Completion Date :||December 2020|
|Estimated Study Completion Date :||July 2021|
peripubertal obese girls
Peripubertal obese girls, aged 8 - 16 years, who are obese (BMI-for-age percentile greater or equal to 95)
- Morning free testosterone [ Time Frame: 0700 to 0900 hours ]
- Insulin-stimulated glucose disposal [ Time Frame: 0900 to 1100 hours ]
- Estimated 24-hour mean insulin concentration [ Time Frame: 24 hours ]
- Luteinizing hormone pulse frequency [ Time Frame: 1800 to 0900 hours ]
- Mean luteinizing hormone concentration [ Time Frame: 1800 to 0900 hours ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00928759
|Contact: Melissa Gilrainemail@example.com|
|Contact: Christopher McCartney, MDfirstname.lastname@example.org|
|United States, Virginia|
|University of Virginia||Recruiting|
|Charlottesville, Virginia, United States, 22908|
|Contact: Melissa Gilrain 434-243-6911 email@example.com|
|Principal Investigator: Christopher McCartney, MD|
|Principal Investigator:||Christopher McCartney, MD||University of Virginia|