Cortisol Regulation in Polycystic Ovary Syndrome (PCOS)

Not Applicable

Completed

• Conditions: Polycystic Ovary Syndrome
• Interventions: Drug: placebo; Drug: pioglitazone; Drug: metformin

• Registration Number: NCT00694759
• Lead Sponsor: 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.

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 Timeline

• Study Start: 2006-10
• Study First Submitted: 2008-06-06
• Study First Submitted QC: 2008-06-09
• Study First Posted: 2008-06-10
• Primary Completion: 2011-06
• Study Completion: 2011-07
• Status Verified: 2019-09
• Last Update Submitted: 2019-09-05
• Last Update Posted: 2019-09-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 37

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
C	placebo	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.
A	pioglitazone	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.
B	metformin	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.

Primary Outcome Measures

Name	Time	Method
The comparison of body surface area adjusted cortisol production rate (CPR/BSA) before insulin sensitizing therapy in women with PCOS.	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.	After 6 months of insulin sensitizing therapy

Secondary Outcome Measures

Name	Time	Method
Comparisons of 24-hour values for adrenocorticotropic hormone , free-cortisol, and cortisol binding globulin.	After 6 months of insulin sensitizing therapy

Trial Locations

Locations (1)

Oregon Health & Science University; 🇺🇸 Portland, Oregon, United States