The serum steroid signature of PCOS hints at the involvement of novel pathways for excess androgen biosynthesis
Open accessAbstract
CONTEXT: Polycystic ovary syndrome (PCOS) is defined by androgen excess and ovarian dysfunction in the absence of a specific physiological diagnosis. The best clinical marker of androgen excess is hirsutism, while the best biochemical parameter is still a matter of debate. Current consensus guidelines recommend, among other hormones, serum free testosterone as an important serum parameter to measure androgen excess. Recently, however, novel active androgens and androgen metabolic pathways have been discovered. OBJECTIVE: To assess the contribution of novel androgens and related steroid biosynthetic pathways to the serum steroid pool in PCOS women in comparison to healthy controls. DESIGN: This is a case control study, wherein PCOS was diagnosed according to the AE-PCOS 2009 criteria. Serum steroid profiling was performed by liquid chromatography high-resolution mass spectrometry. SETTING: Yeditepe University and associated clinics in Istanbul, Turkey, together with Bern University Hospital Inselspital, Bern, Switzerland. PARTICIPANTS: 42 PCOS women and 42 matched, healthy control women. MAIN OUTCOME MEASURES: Assessment of 34 steroids compartmentalized in four androgen related pathways: the classic androgen pathway, the backdoor pathway, the C11-oxy backdoor pathway, and the C11-oxy (11β-hydroxyandrostenedione) pathway. RESULTS: Metabolites of all four pathways were identified in healthy and PCOS women. Highest concentrations were found for progesterone in controls and androstenedione in PCOS. Lowest levels were found for 11-ketotestosterone in controls compared to PCOS, and for 20α-hydroxyprogesterone in PCOS compared to controls. PCOS also had higher serum testosterone levels compared to the controls. PCOS women had overall higher levels of steroid metabolites of all four androgen pathways compared to healthy controls. CONCLUSIONS: Novel alternative pathways contribute to the androgen production in healthy and PCOS women. Hyperandrogenism in PCOS is characterized by an overall increase of serum androgens in the classic, backdoor and C11-oxy pathways. While monogenetic disorders of steroid biosynthesis can be recognized by a specific pattern in the steroid profile, no diagnostic pattern or classifier was found in the serum for PCOS.
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Methods allowing measurement of comprehensive steroid panels comprising multiple steroid metabolites obtained by single runs are ideal for recognizing patterns of steroid disorders such as CAH or PCOS.
“Methods allowing the measurement of comprehensive steroid panels comprising multiple steroid metabolites obtained by single runs are ideal for recognizing patterns of steroid disorders such as CAH or PCOS [33,37,38].”
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- Authors
- Altinkilic, E. M., du Toit, T., Sakin, Ö., Attar, R., Groessl, M., & Flück, C. E.
- Affiliations
- Acıbadem University (TR)
- University of Bern (CH)
- Corresponding author
- Flück, Christa E.
- Venue
- The Journal of Steroid Biochemistry and Molecular Biology
- Publisher
- Elsevier BV
- Published
- 2023-10
- Volume
- 233
- Pages
- 106366
- ISSN
- 0960-0760 (ISSN-L)
- OpenAlex
- W4385248933
- Cited by
- 22
- References
- 62
- Citations by year
- 2026: 7 · 2025: 6 · 2024: 8 · 2023: 1
- FWCI
- 5.27
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- The Journal of Steroid Biochemistry and Molecular Biology (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Yeditepe University Institutional Repository (submittedVersion, other-oa)
- Funders
- University of Bern
- H2020 Marie Skłodowska-Curie Actions (101023999)
- 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, androgen production, 11β-hydroxyandrostenedione, androstenedione, 11-ketotestosterone, 20alpha-dihydroprogesterone, free testosterone, steroid metabolites
- MeSH terms
- Androgens, Female, Humans, Polycystic Ovary Syndrome, Steroids, Testosterone, Case-Control Studies, Hyperandrogenism
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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