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Cited by 110Ovarian function and disordersAdrenal Hormones and DisordersSexual Differentiation and Disorders

Increased 5α-Reductase Activity and Adrenocortical Drive in Women with Polycystic Ovary Syndrome

Vassiliadi, Dimitra A., Barber, Thomas M., Hughes, Beverly A., McCarthy, Mark I., Wass, John A. H., Franks, Stephen, Nightingale, Peter, Tomlinson, Jeremy W. +2 more·2009·The Journal of Clinical Endocrinology & Metabolism
DOI 10.1210/jc.2009-0837
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Abstract

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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Crossref · 10.1210/jc.2009-0837

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  • Systemic upregulation of 5α-reductase activity is observed in women with PCOS leading to enhanced glucocorticoid clearance and enhanced androgen activation in peripheral tissues.

    “Systemic upregulation of 5α-reductase activity is observed in women with PCOS leading to enhanced glucocorticoid clearance and enhanced androgen activation in peripheral tissues (Fassnacht et al., 2003, Stewart et al., 1990, Vassiliadi et al., 2009)”

    From Intracrine androgen biosynthesis, metabolism and action revisited (2018) · cites this paper as Vassiliadi et al., 2009

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Authors
Vassiliadi, D. A., Barber, T. M., Hughes, B. A., McCarthy, M. I., Wass, J. A. H., Franks, S., Nightingale, P., Tomlinson, J. W., Arlt, W., & Stewart, P. M.
Affiliations
  • University of Birmingham (GB)
  • University of Oxford (GB)
  • Imperial College London (GB)
  • National Health Service (GB)
Corresponding author
Stewart, Paul M.
ORCID
Venue
The Journal of Clinical Endocrinology & Metabolism
Publisher
The Endocrine Society
Published
2009-09-01
Volume
94
Issue
9
Pages
3558-3566
ISSN
  • 0021-972X (ISSN-L)
  • 1945-7197
DOI
10.1210/jc.2009-0837
OpenAlex
W2153159631
Cited by
110
References
37
Citations by year
2025: 5 · 2024: 3 · 2023: 5 · 2022: 6 · 2021: 4 · 2020: 7 · 2019: 7 · 2018: 5 · 2017: 9 · 2016: 13 · 2015: 9 · 2014: 13 · 2013: 4 · 2012: 5
FWCI
7.39
Type
journal article
Language
en
Open access
closed
Locations
  • The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
  • PubMed (publishedVersion)
  • University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
Funders
  • Wellcome Trust (082809/Z/07/Z, 075322/Z/04/Z)
  • National Institute for Health and Care Research (NF-SI-0508-10356)
  • Novo Nordisk UK Research Foundation
  • University of Oxford
  • Novo Nordisk
  • Medical Research Council
Topics
  • Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
Keywords
polycystic ovary syndrome, 5alpha-reductase activity, 11β-hydroxysteroid dehydrogenase, cortisol metabolism, glucocorticoid metabolism, androgen metabolism, obesity, hyperandrogenism, insulin resistance, HOMA, urinary steroid metabolites, dehydroepiandrosterone sulfate, dehydroepiandrosterone
MeSH terms
Adolescent, Adult, Androgens, Cross-Sectional Studies, Female, Glucocorticoids, Humans, Hydrocortisone, Middle Aged, Obesity, Polycystic Ovary Syndrome, Cholestenone 5 alpha-Reductase

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