Cortisol Regulation in Polycystic Ovary Syndrome (PCOS)

Polycystic Ovary Syndrome Clinical Trial

Official title:

Cortisol Regulation in Polycystic Ovary Syndrome

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00694759
• Other study ID #: OHSUIRB00002532
• Status: Completed
• Phase: N/A
• Start date: October 2006
• Est. completion date: July 2011

Study information

• Verified date: September 2019
• Source: Oregon Health and Science University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 37
• Est. completion date: July 2011
• Est. primary completion date: June 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 45 Years

Eligibility

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.

Related Conditions & MeSH terms

• Polycystic Ovary Syndrome
• Syndrome

Intervention

Drug:
• pioglitazone
30 mg for 2 weeks, then 45 mg daily
• metformin
500mg twice daily for 1 week, then 1000 mg twice daily
• placebo
capsule twice daily

Locations

Country	Name	City	State
United States	Oregon Health & Science University	Portland	Oregon

Sponsors (1)

Lead Sponsor	Collaborator
Oregon Health and Science University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Comparisons of 24-hour values for adrenocorticotropic hormone , free-cortisol, and cortisol binding globulin.		Before 6 months of insulin sensitizing therapy
Secondary	Comparisons of 24-hour values for adrenocorticotropic hormone , free-cortisol, and cortisol binding globulin.		After 6 months of insulin sensitizing therapy