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Cited by 158Ovarian function and disordersAdrenal Hormones and DisordersSexual Differentiation and Disorders

Beyond Adrenal and Ovarian Androgen Generation: Increased Peripheral 5α-Reductase Activity in Women with Polycystic Ovary Syndrome

Fassnacht, Martin, Schlenz, Nadine, Schneider, Susanne B., Wudy, Stefan A., Allolio, Bruno, Arlt, Wiebke·2003·The Journal of Clinical Endocrinology & Metabolism
DOI 10.1210/jc.2002-021875
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Abstract

Hyperandrogenism, a main clinical feature of polycystic ovary syndrome (PCOS), is thought to result from enhanced ovarian and adrenal androgen generation. To investigate the contribution of peripheral steroidogenesis, we used an oral challenge with dehydroepiandrosterone (DHEA) and analyzed its downstream conversion toward androgens in eight women with PCOS (age, 20-32 yr; body mass index, 20-41 kg/m(2)) and eight healthy women matched for age and body mass index. They underwent frequent serum sampling and urine collection for 8 h on three occasions: at baseline, and after 4 d of dexamethasone (Dex; 4 x 0.5 mg/d), followed by ingestion of 100 mg DHEA or placebo. Dex induced similar significant suppression of circulating steroids in both groups. The oral DHEA challenge led to similar significant increases in the area under the concentration-time curve (0-8 h after Dex) of serum DHEA, DHEA sulfate, androstenedione, and testosterone. However, after oral DHEA, PCOS women had significantly higher increases in serum 5 alpha-dihydrotestosterone (P < 0.01), its main metabolite androstanediol glucuronide (P < 0.05), and the 5 alpha-reduced urinary androgen metabolite androsterone (P < 0.05). PCOS women also had significantly higher baseline excretion of 5 alpha-reduced glucocorticoid (P < 0.01) and mineralocorticoid metabolites (P < 0.05). Taken together, these data indicate enhanced peripheral 5 alpha-reductase activity in PCOS. Thus, not only ovary and adrenal, but also liver and peripheral target tissues, significantly contribute to steroid alterations in PCOS.

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Crossref · 10.1210/jc.2002-021875

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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 Fassnacht et al., 2003

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Authors
Fassnacht, M., Schlenz, N., Schneider, S. B., Wudy, S. A., Allolio, B., & Arlt, W.
Affiliations
  • University of Würzburg (DE)
  • Justus-Liebig-Universität Gießen (DE)
Corresponding author
Arlt, Wiebke
ORCID
Venue
The Journal of Clinical Endocrinology & Metabolism
Publisher
The Endocrine Society
Published
2003-06
Volume
88
Issue
6
Pages
2760-2766
ISSN
  • 0021-972X (ISSN-L)
  • 1945-7197
DOI
10.1210/jc.2002-021875
OpenAlex
W2071127270
Semantic Scholar
f71e52ebb8983b637159247bd4a1df1fb6efa0ec
Cited by
158
References
31
Citations by year
2026: 5 · 2025: 1 · 2024: 3 · 2023: 4 · 2022: 4 · 2021: 5 · 2020: 7 · 2019: 5 · 2018: 5 · 2017: 13 · 2016: 16 · 2015: 12 · 2014: 8 · 2013: 7 · 2012: 7
FWCI
6.43
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)
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, hyperandrogenism, 5α-reductase, dihydrotestosterone, androstanediol glucuronide, androsterone, glucocorticoid metabolites, dexamethasone suppression
MeSH terms
Adult, Androgens, Dehydroepiandrosterone, Dexamethasone, Female, Glucocorticoids, Hormones, Humans, Oxidoreductases, Polycystic Ovary Syndrome, Dihydrotestosterone, Cross-Over Studies, Cholestenone 5 alpha-Reductase

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