Cortisol Regulation in Polycystic Ovary Syndrome
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.
Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Basic Science
The comparison of body surface area adjusted cortisol production rate (CPR/BSA) before and after insulin sensitizing therapy in women with PCOS.
Before and after 6 months of insulin sensitizing therapy
Bethany J. Klopfenstein, MD
Oregon Health and Science University
United States: Institutional Review Board
|Oregon Health & Science University||Portland, Oregon 97201|