Cortisol Regulation in Polycystic Ovary Syndrome (PCOS)

NCT ID: NCT00694759

Last Updated: 2019-09-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 37 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-10-31
• Study Completion Date: 2011-07-31

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.

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.

Conditions

Polycystic Ovary Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

pioglitazone

Intervention Type: DRUG

30 mg for 2 weeks, then 45 mg daily

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.

Group Type: ACTIVE_COMPARATOR

metformin

Intervention Type: DRUG

500mg twice daily for 1 week, then 1000 mg twice daily

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.

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

capsule twice daily

Interventions

pioglitazone

30 mg for 2 weeks, then 45 mg daily

Intervention Type: DRUG

metformin

500mg twice daily for 1 week, then 1000 mg twice daily

Intervention Type: DRUG

placebo

capsule twice daily

Intervention Type: DRUG

Other Intervention Names

Actos; Glucophage; Glucophage XR

Eligibility Criteria

Inclusion Criteria

• 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

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

Exclusion Criteria

• 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

• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Oregon Health and Science University

OTHER

Sponsor Role: lead

Responsible Party

Bethany Klopfenstein

MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Bethany J. Klopfenstein, MD

Role: PRINCIPAL_INVESTIGATOR

Oregon Health and Science University

Locations

Oregon Health & Science University

Portland, Oregon, United States

Countries

United States

Other Identifiers

OHSUIRB00002532

Identifier Type: -

Identifier Source: org_study_id