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Increased 5α-reductase activity and adrenocortical drive in women with polycystic ovary syndrome
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Vassiliadi, Dimitra A., Barber, T. M., Hughes, Beverly A., McCarthy, Mark I., Wass, John A. H., Franks, Stephen, Nightingale, Peter, Tomlinson, Jeremy W., Arlt, Wiebke and Stewart, Paul M. (2009) Increased 5α-reductase activity and adrenocortical drive in women with polycystic ovary syndrome. The Journal of Clinical Endocrinology & Metabolism, 94 (9). pp. 3558-3566. doi:10.1210/jc.2009-0837 ISSN 0021-972X.
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Official URL: http://dx.doi.org/10.1210/jc.2009-0837
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, 5α-reductase, and 11β-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 μg/24 h for the nonobese; 5,547 ± 2,911 vs. 2,468 ± 1,794 μg/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 μg/24 h; P = 0.001). 5α-Reductase activity correlated with BMI, insulin levels, and homeostasis model assessment. Both obese and nonobese PCOS patients had higher 5α-reductase activity than controls (all P < 0.05). 11β-Hydroxysteroid dehydrogenase activities did not differ between PCOS and controls.
Conclusions: PCOS is associated with enhanced androgen and cortisol metabolite excretion and increased 5α-reductase activity that cannot be explained by obesity alone. Increased adrenal corticosteroid production represents an important pathogenic pathway in PCOS.
| Item Type: | Journal Article | ||||
|---|---|---|---|---|---|
| Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine > Metabolic and Vascular Health (- until July 2016) Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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| Journal or Publication Title: | The Journal of Clinical Endocrinology & Metabolism | ||||
| Publisher: | The Endocrine Society | ||||
| ISSN: | 0021-972X | ||||
| Official Date: | 2009 | ||||
| Dates: |
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| Volume: | 94 | ||||
| Number: | 9 | ||||
| Page Range: | pp. 3558-3566 | ||||
| DOI: | 10.1210/jc.2009-0837 | ||||
| Status: | Peer Reviewed | ||||
| Publication Status: | Published | ||||
| Access rights to Published version: | Restricted or Subscription Access |
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