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Steroid profiles in ovarian follicular fluid in women with and without polycystic ovary syndrome, analyzed by liquid chromatography-tandem mass spectrometry.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. (Gynekologisk endokrinologi/Naessén)
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
Donetsk State Medical University, Ukraine.
Donetsk State Medical University, Ukraine.
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2010 (English)In: Fertility and Sterility, ISSN 0015-0282, Vol. 94, no 6, 2228-2233 p.Article in journal (Refereed) Published
Abstract [en]


To compare steroid concentrations and steroid product-to-precursor ratios in ovarian follicular fluid (FF) from women with polycystic ovary syndrome (PCOS) and from regularly menstruating women in their early follicular phase, using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Polycystic ovary syndrome involves abnormal regulation of the steroidogenic enzymes, leading to arrest of follicle development.


Case-control study.


University hospital clinic.


Follicular fluid from size-matched ovarian follicles (5-8 mm) in 27 nonstimulated women with PCOS and in 21 women without PCOS was sampled. Thirteen steroids were quantitated from 40 muL of FF, using LC-MS/MS.




Concentrations of steroids in the FF and product-to-precursor ratios (enzyme activity) were compared between the groups.


In women with PCOS, ovarian FF contained higher concentrations of individual and total androgens, lower individual and total estrogens (E), and a lower total E-to-androgen ratio, compared with regularly menstruating women. The product-to-precursor concentration ratios indicated higher CYP17-linked and lower CYP19-linked (aromatase) enzyme activity. Receiver operating characteristic plots indicated the early CYP17 step (17-OH5P/5P) being highly important for the prevalence of PCOS (c = 0.95).


The women with PCOS had higher ovarian CYP17-linked and lower CYP19-linked (aromatase) enzyme activity, confirming previous data. Multiple steroid assessments from minute volumes including FF from nonstimulated ovaries, using LC-MS/MS, might be useful in research, clinical endocrinology, and in IVF.

Place, publisher, year, edition, pages
2010. Vol. 94, no 6, 2228-2233 p.
Keyword [en]
Androgens, CYP17, CYP19, estrogens, follicular fluid, LC-MS/MS, mass spectrometry, PCOS, Polycystic ovary syndrome, steroid hormones
National Category
Engineering and Technology Obstetrics, Gynecology and Reproductive Medicine Other Basic Medicine
URN: urn:nbn:se:uu:diva-126541DOI: 10.1016/j.fertnstert.2009.12.081ISI: 000283441400054PubMedID: 20171618OAI: oai:DiVA.org:uu-126541DiVA: diva2:324701
Published online 19 February 2010Available from: 2010-06-16 Created: 2010-06-16 Last updated: 2011-08-04Bibliographically approved
In thesis
1. Mass Spectrometric Applications for Diagnosing Metabolic and Endocrine Diseases
Open this publication in new window or tab >>Mass Spectrometric Applications for Diagnosing Metabolic and Endocrine Diseases
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Disease-specific compounds (biomarkers) are analyzed in clinical laboratories to assist with diagnosing diseases. This thesis describes development and validation of liquid chromatography tandem mass spectrometry (LC-MS/MS) based tests for diagnosing a diverse group of endocrine and metabolic diseases. The analytical methods used on-line and off-line sample extraction and analytical derivatization as means of enhancing the analytical sensitivity, specificity and clinical utility. All developed methods were extensively validated and reference intervals for the biomarker concentrations were established in blood samples of healthy adults and children. Advantages of the LC-MS/MS as an analytical technique include possibility of simultaneous measurement of multiple analytes and ability of confirming their identity. In this thesis we proposed and evaluated approaches for the assessment of the specificity of analysis in the methods that use tandem mass spectrometry detection. To enhance throughput of the LC-MS/MS tests for the biomarkers that have endogenous or exogenous isomers an approach was developed for quantitation of isomers from unresolved chromatographic peaks. Using methods developed in this thesis we performed a study of the steroidogenesis in ovarian follicles of healthy women and women with polycystic ovary syndrome (PCOS). Obtained data on the steroid concentrations and associations between the steroid metabolites in the pathway would be helpful for better understanding of the ovarian pathophysiology. Potential biomarkers of PCOS were identified in the thesis; further studies will be necessary to confirm their clinical utility.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2008. 80 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 426
Analytical chemistry, biomarker, liquid chromatography, tandem mass spectrometry, LC-MS/MS, sample preparation, isomers, steroid hormones, congenital adrenal hyperplasia, polycystic ovary syndrome, Analytisk kemi
urn:nbn:se:uu:diva-8658 (URN)978-91-554-7172-9 (ISBN)
Public defence
2008-05-16, BMC B:41, BMC, Husargatan 3, SE-751 24, Uppsala, Sweden, 10:15
Available from: 2008-04-22 Created: 2008-04-22 Last updated: 2011-05-10Bibliographically approved

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Naessén, TordBergquist, JonasKirilovas, Dmitrijus
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