Cortisol Regulation in Polycystic Ovary Syndrome (PCOS)

Overview[ - collapse ][ - ]

Purpose 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.
ConditionPolycystic Ovary Syndrome
InterventionDrug: pioglitazone
Drug: metformin
Drug: placebo
PhaseN/A
SponsorOregon Health and Science University
Responsible PartyOregon Health and Science University
ClinicalTrials.gov IdentifierNCT00694759
First ReceivedJune 6, 2008
Last UpdatedAugust 3, 2010
Last verifiedAugust 2010

Tracking Information[ + expand ][ + ]

First Received DateJune 6, 2008
Last Updated DateAugust 3, 2010
Start DateOctober 2006
Estimated Primary Completion DateJuly 2011
Current Primary Outcome MeasuresThe comparison of body surface area adjusted cortisol production rate (CPR/BSA) before and after insulin sensitizing therapy in women with PCOS. [Time Frame: Before and after 6 months of insulin sensitizing therapy] [Designated as safety issue: No]
Current Secondary Outcome MeasuresComparisons of 24-hour values for adrenocorticotropic hormone , free-cortisol, and cortisol binding globulin. [Time Frame: Before and after 6 months of insulin sensitizing therapy] [Designated as safety issue: No]

Descriptive Information[ + expand ][ + ]

Brief TitleCortisol Regulation in Polycystic Ovary Syndrome (PCOS)
Official TitleCortisol Regulation in Polycystic Ovary Syndrome
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 TypeInterventional
Study PhaseN/A
Study DesignAllocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Basic Science
ConditionPolycystic Ovary Syndrome
InterventionDrug: pioglitazone
30 mg for 2 weeks, then 45 mg daily
Other Names:
ActosDrug: metformin
500mg twice daily for 1 week, then 1000 mg twice daily
Other Names:
  • Glucophage
  • Glucophage XR
Drug: placebo
capsule twice daily
Study Arm (s)
  • 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.
  • 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.
  • 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.

Recruitment Information[ + expand ][ + ]

Recruitment StatusRecruiting
Estimated Enrollment107
Estimated Completion DateJuly 2011
Estimated Primary Completion DateJune 2011
Eligibility 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.
GenderFemale
Ages18 Years
Accepts Healthy VolunteersAccepts Healthy Volunteers
ContactsContact: Bethany J Klopfenstein, MD
503-494-4020
klopfens@ohsu.edu
Location CountriesUnited States

Administrative Information[ + expand ][ + ]

NCT Number NCT00694759
Other Study ID NumbersOHSUIRB00002532
Has Data Monitoring CommitteeNo
Information Provided ByOregon Health and Science University
Study SponsorOregon Health and Science University
CollaboratorsNot Provided
Investigators Principal Investigator: Bethany J. Klopfenstein, MD Oregon Health and Science University
Verification DateAugust 2010

Locations[ + expand ][ + ]

Oregon Health & Science University
Portland, Oregon, United States, 97239
Principal Investigator: Bethany J. Klopfenstein, MD
Recruiting