Cortisol Regulation in Polycystic Ovary Syndrome (PCOS)

September 5, 2019 updated by: Bethany Klopfenstein, Oregon Health and Science University

Cortisol Regulation in Polycystic Ovary Syndrome

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

37

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Oregon
      • Portland, Oregon, United States, 97239
        • Oregon Health & Science University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years to 41 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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 Names:
  • 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
Before 6 months of insulin sensitizing therapy
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
After 6 months of insulin sensitizing therapy

Secondary Outcome Measures

Outcome Measure
Time Frame
Comparisons of 24-hour values for adrenocorticotropic hormone , free-cortisol, and cortisol binding globulin.
Time Frame: Before 6 months of insulin sensitizing therapy
Before 6 months of insulin sensitizing therapy
Comparisons of 24-hour values for adrenocorticotropic hormone , free-cortisol, and cortisol binding globulin.
Time Frame: After 6 months of insulin sensitizing therapy
After 6 months of insulin sensitizing therapy

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Oregon Health and Science University

Investigators

  • Principal Investigator: Bethany J. Klopfenstein, MD, Oregon Health and Science University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2006

Primary Completion (Actual)

June 1, 2011

Study Completion (Actual)

July 1, 2011

Study Registration Dates

First Submitted

June 6, 2008

First Submitted That Met QC Criteria

June 9, 2008

First Posted (Estimate)

June 10, 2008

Study Record Updates

Last Update Posted (Actual)

September 9, 2019

Last Update Submitted That Met QC Criteria

September 5, 2019

Last Verified

September 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • OHSUIRB00002532

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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