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Cortisol Regulation in Polycystic Ovary Syndrome (PCOS)

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ClinicalTrials.gov Identifier: NCT00694759
Recruitment Status : Completed
First Posted : June 10, 2008
Last Update Posted : September 9, 2019
Sponsor:
Information provided by (Responsible Party):
Bethany Klopfenstein, Oregon Health and Science University

Brief Summary:
The purpose of this study is to determine if insulin resistance (how well the body uses insulin and clears sugar) can affect cortisol levels in normal healthy women and women with polycystic ovary syndrome of all body weights.

Condition or disease Intervention/treatment Phase
Polycystic Ovary Syndrome Drug: pioglitazone Drug: metformin Drug: placebo Not Applicable

Detailed Description:

PCOS is a common clinical problem affecting young women, characterized by oligomenorrhea and hyperandrogenism. Central obesity and insulin resistance are also prominent features of PCOS, and in addition are important risk factors for development of hypertension, hyperlipidemia and atherosclerotic heart disease. Previous studies have suggested that cortisol is dysregulated in PCOS, primarily through increased hypothalamic-pituitary-adrenal (HPA) axis activity and enhanced cortisol secretion. Increased adrenocorticotropic hormone (ACTH) secretion could also potentially lead to elevated adrenal androgen production in PCOS. Techniques used in previous studies have been inconsistent, however, and a link between increased HPA axis activity and the phenotypic changes in PCOS has not been clearly demonstrated. Cortisol is also produced from cortisone in peripheral adipose tissue by the enzyme 11beta-hydroxysteroid dehydrogenase type 1 (HSD 1), suggesting another potential point of dysregulation that may contribute to central obesity and insulin resistance in PCOS. Further investigation of both central and peripheral regulation of cortisol is necessary to better understand the pathophysiology of PCOS.

Specific Aim 1: To perform a cross-sectional study of women with PCOS and normal controls matched for age and body mass index, and measure insulin sensitivity and visceral fat, as well as (a) 24-hour CPR, ACTH, free cortisol, and cortisol binding globulin (CBG), (b) adipocyte, liver, and whole body HSD 1 activity, and (c) androgen levels.

Specific Aim 2: To prospectively administer pioglitazone or metformin to women with PCOS in a placebo-controlled trial, and after one month and six months of therapy measure (a) 24-hour CPR, ACTH, free cortisol, and CBG, (b) adipocyte, liver, and whole body HSD 1 activity, and (c) insulin sensitivity, visceral fat, and androgen levels.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 37 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Cortisol Regulation in Polycystic Ovary Syndrome
Study Start Date : October 2006
Actual Primary Completion Date : June 2011
Actual Study Completion Date : July 2011


Arm Intervention/treatment
Active Comparator: A
Pioglitazone will be given to women with PCOS. After one month and six months of therapy, measure (a) 24-hour CPR, ACTH, free cortisol, and CBG, (b) adipocyte, liver, and whole body HSD 1 activity, and (c) insulin sensitivity, visceral fat, and androgen levels.
Drug: pioglitazone
30 mg for 2 weeks, then 45 mg daily
Other Name: Actos

Active Comparator: B
Metformin will be given to women with PCOS. After one month and six months of therapy, measure (a) 24-hour CPR, ACTH, free cortisol, and CBG, (b) adipocyte, liver, and whole body HSD 1 activity, and (c) insulin sensitivity, visceral fat, and androgen levels.
Drug: metformin
500mg twice daily for 1 week, then 1000 mg twice daily
Other Names:
  • Glucophage
  • Glucophage XR

Placebo Comparator: C
Placebo will be given to women with PCOS. After one month and six months of therapy, measure (a) 24-hour CPR, ACTH, free cortisol, and CBG, (b) adipocyte, liver, and whole body HSD 1 activity, and (c) insulin sensitivity, visceral fat, and androgen levels.
Drug: placebo
capsule twice daily




Primary Outcome Measures :
  1. The comparison of body surface area adjusted cortisol production rate (CPR/BSA) before insulin sensitizing therapy in women with PCOS. [ Time Frame: Before 6 months of insulin sensitizing therapy ]
  2. The comparison of body surface area adjusted cortisol production rate (CPR/BSA) after insulin sensitizing therapy in women with PCOS. [ Time Frame: After 6 months of insulin sensitizing therapy ]

Secondary Outcome Measures :
  1. Comparisons of 24-hour values for adrenocorticotropic hormone , free-cortisol, and cortisol binding globulin. [ Time Frame: Before 6 months of insulin sensitizing therapy ]
  2. Comparisons of 24-hour values for adrenocorticotropic hormone , free-cortisol, and cortisol binding globulin. [ Time Frame: After 6 months of insulin sensitizing therapy ]


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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria (Healthy controls):

  • Healthy
  • At lifetime maximal weight
  • Weight stable for at least 6 months prior to study entry
  • Willing to commit to not making significant changes to their diet or daily activities while enrolled.
  • Premenopausal
  • Have regular menstrual cycles
  • No evidence of hirsutism

Additional Inclusion Criteria (Subjects with PCOS):

  • Clinical findings of amenorrhea or oligomenorrhea dating from menarche
  • Clinical and/or biochemical evidence of hyperandrogenism
  • Exclusion of related disorders

Exclusion Criteria (Healthy controls):

  • Less than 18 years of age
  • Exercise > 30 minutes/day, 3 times a week
  • Smokers
  • Heavy alcohol drinkers (> 2 drinks/day)
  • Type 2 diabetes
  • Medical diagnoses including heart disease and cancer
  • Psychiatric illness (i.e.depression, psychosis, bipolar, schizophrenia)
  • Body weight > 136 kg
  • Pregnant
  • Endocrine diseases affecting body composition or androgen levels

Additional Exclusion Criteria (Subjects with PCOS):

  • Laboratory evidence of hyperprolactinemia, thyroid dysfunction, or 21-hydroxylase-deficient nonclassic CAH
  • Contraindication to pioglitazone (i.e. CHF, impaired liver function, anemia, depressed leukocyte counts, pulmonary disease, known sensitivity to thiazolidinediones.

Information from the National Library of Medicine

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): NCT00694759


Locations
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United States, Oregon
Oregon Health & Science University
Portland, Oregon, United States, 97239
Sponsors and Collaborators
Oregon Health and Science University
Investigators
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Principal Investigator: Bethany J. Klopfenstein, MD Oregon Health and Science University

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Responsible Party: Bethany Klopfenstein, MD, Oregon Health and Science University
ClinicalTrials.gov Identifier: NCT00694759    
Other Study ID Numbers: OHSUIRB00002532
First Posted: June 10, 2008    Key Record Dates
Last Update Posted: September 9, 2019
Last Verified: September 2019
Keywords provided by Bethany Klopfenstein, Oregon Health and Science University:
Polycystic ovary syndrome
insulin
PCOS
cortisol regulation
regulation
Additional relevant MeSH terms:
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Polycystic Ovary Syndrome
Syndrome
Disease
Pathologic Processes
Ovarian Cysts
Cysts
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Gonadal Disorders
Endocrine System Diseases
Insulin
Metformin
Pioglitazone
Hydrocortisone
Hydrocortisone 17-butyrate 21-propionate
Hydrocortisone acetate
Hydrocortisone hemisuccinate
Hypoglycemic Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents