Increased 5 alpha-reductase activity and adrenocortical drive in women with polycystic ovary syndrome.

CONTEXT: Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism, anovulation, and susceptibility to the metabolic syndrome. Altered peripheral cortisol metabolism has been reported in PCOS, but also in simple obesity. OBJECTIVE: The aim of the study was to describe cortisol metabolis...

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Autores principales: Vassiliadi, D, Barber, T, Hughes, B, McCarthy, M, Wass, J, Franks, S, Nightingale, P, Tomlinson, J, Arlt, W, Stewart, P
Formato: Journal article
Lenguaje:English
Publicado: 2009
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author Vassiliadi, D
Barber, T
Hughes, B
McCarthy, M
Wass, J
Franks, S
Nightingale, P
Tomlinson, J
Arlt, W
Stewart, P
author_facet Vassiliadi, D
Barber, T
Hughes, B
McCarthy, M
Wass, J
Franks, S
Nightingale, P
Tomlinson, J
Arlt, W
Stewart, P
author_sort Vassiliadi, D
collection OXFORD
description CONTEXT: Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism, anovulation, and susceptibility to the metabolic syndrome. Altered peripheral cortisol metabolism has been reported in PCOS, but also in simple obesity. OBJECTIVE: The aim of the study was to describe cortisol metabolism and metabolic characteristics of a large PCOS cohort and to delineate the effect of obesity by comparison to body mass index (BMI)-matched controls. DESIGN AND SETTING: We conducted an observational, cross-sectional study at outpatient clinics of two secondary/tertiary care centers. PATIENTS OR OTHER PARTICIPANTS: A total of 178 PCOS patients fulfilling Rotterdam criteria and 100 BMI-matched controls participated in the study. INTERVENTION: The study included 24-h urine collection for steroid metabolite excretion and fasting blood samples, followed by an oral glucose tolerance test. MAIN OUTCOME MEASURES: We measured urinary steroid metabolites including glucocorticoids and androgens and the ratios reflecting enzymatic activities involved in peripheral cortisol and androgen metabolism, 5 alpha-reductase, and 11 beta-hydroxysteroid dehydrogenase types 1 and 2. We also measured circulating levels of glucose, insulin, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and testosterone and calculated homeostasis model assessment. RESULTS: Total androgen metabolites were higher in PCOS patients compared to BMI-matched controls (4,105 +/- 2,047 vs. 2,532 +/- 1,610 microg/24 h for the nonobese; 5,547 +/- 2,911 vs. 2,468 +/- 1,794 microg/24 h for the obese; both P < 0.001). Total glucocorticoid metabolites were higher in obese PCOS vs. controls (10,786 +/- 3,852 vs. 8,834 +/- 4,487 microg/24 h; P = 0.001). 5 alpha-Reductase activity correlated with BMI, insulin levels, and homeostasis model assessment. Both obese and nonobese PCOS patients had higher 5 alpha-reductase activity than controls (all P < 0.05). 11 beta-Hydroxysteroid dehydrogenase activities did not differ between PCOS and controls. CONCLUSIONS: PCOS is associated with enhanced androgen and cortisol metabolite excretion and increased 5 alpha-reductase activity that cannot be explained by obesity alone. Increased adrenal corticosteroid production represents an important pathogenic pathway in PCOS.
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spelling oxford-uuid:b0f8eac1-636d-4e41-89c2-007be44644552022-03-27T04:00:27ZIncreased 5 alpha-reductase activity and adrenocortical drive in women with polycystic ovary syndrome.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:b0f8eac1-636d-4e41-89c2-007be4464455EnglishSymplectic Elements at Oxford2009Vassiliadi, DBarber, THughes, BMcCarthy, MWass, JFranks, SNightingale, PTomlinson, JArlt, WStewart, P CONTEXT: Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism, anovulation, and susceptibility to the metabolic syndrome. Altered peripheral cortisol metabolism has been reported in PCOS, but also in simple obesity. OBJECTIVE: The aim of the study was to describe cortisol metabolism and metabolic characteristics of a large PCOS cohort and to delineate the effect of obesity by comparison to body mass index (BMI)-matched controls. DESIGN AND SETTING: We conducted an observational, cross-sectional study at outpatient clinics of two secondary/tertiary care centers. PATIENTS OR OTHER PARTICIPANTS: A total of 178 PCOS patients fulfilling Rotterdam criteria and 100 BMI-matched controls participated in the study. INTERVENTION: The study included 24-h urine collection for steroid metabolite excretion and fasting blood samples, followed by an oral glucose tolerance test. MAIN OUTCOME MEASURES: We measured urinary steroid metabolites including glucocorticoids and androgens and the ratios reflecting enzymatic activities involved in peripheral cortisol and androgen metabolism, 5 alpha-reductase, and 11 beta-hydroxysteroid dehydrogenase types 1 and 2. We also measured circulating levels of glucose, insulin, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and testosterone and calculated homeostasis model assessment. RESULTS: Total androgen metabolites were higher in PCOS patients compared to BMI-matched controls (4,105 +/- 2,047 vs. 2,532 +/- 1,610 microg/24 h for the nonobese; 5,547 +/- 2,911 vs. 2,468 +/- 1,794 microg/24 h for the obese; both P < 0.001). Total glucocorticoid metabolites were higher in obese PCOS vs. controls (10,786 +/- 3,852 vs. 8,834 +/- 4,487 microg/24 h; P = 0.001). 5 alpha-Reductase activity correlated with BMI, insulin levels, and homeostasis model assessment. Both obese and nonobese PCOS patients had higher 5 alpha-reductase activity than controls (all P < 0.05). 11 beta-Hydroxysteroid dehydrogenase activities did not differ between PCOS and controls. CONCLUSIONS: PCOS is associated with enhanced androgen and cortisol metabolite excretion and increased 5 alpha-reductase activity that cannot be explained by obesity alone. Increased adrenal corticosteroid production represents an important pathogenic pathway in PCOS.
spellingShingle Vassiliadi, D
Barber, T
Hughes, B
McCarthy, M
Wass, J
Franks, S
Nightingale, P
Tomlinson, J
Arlt, W
Stewart, P
Increased 5 alpha-reductase activity and adrenocortical drive in women with polycystic ovary syndrome.
title Increased 5 alpha-reductase activity and adrenocortical drive in women with polycystic ovary syndrome.
title_full Increased 5 alpha-reductase activity and adrenocortical drive in women with polycystic ovary syndrome.
title_fullStr Increased 5 alpha-reductase activity and adrenocortical drive in women with polycystic ovary syndrome.
title_full_unstemmed Increased 5 alpha-reductase activity and adrenocortical drive in women with polycystic ovary syndrome.
title_short Increased 5 alpha-reductase activity and adrenocortical drive in women with polycystic ovary syndrome.
title_sort increased 5 alpha reductase activity and adrenocortical drive in women with polycystic ovary syndrome
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