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      Free Testosterone Reflects Metabolic as well as Ovarian Disturbances in Subfertile Oligomenorrheic Women

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          Abstract

          Background

          Diagnosing polycystic ovary syndrome (PCOS) is based on ovulatory dysfunction, ovarian ultrasound data, and androgen excess. Total testosterone is frequently used to identify androgen excess, but testosterone is mainly bound to sex hormone-binding globulin (SHBG) and albumin. Only 1-2% of nonprotein-bound testosterone (so-called free testosterone) is biologically active and responsible for androgen action. Moreover, automated immunoassays which are frequently used for female testosterone measurements are inaccurate.

          Objective

          To assess the clinical usefulness of liquid chromatography-tandem mass spectrometry measured testosterone and calculated free testosterone in subfertile women attending a fertility clinic with oligomenorrhea and suspected PCOS.

          Methods

          Hormonal and metabolic parameters were evaluated, and ovarian ultrasound was performed. Total testosterone was measured by liquid chromatography-tandem mass spectrometry. Free testosterone was calculated from total testosterone and SHBG.

          Results

          Sixty-six women were included in the study. Total testosterone was associated with ovarian volume and antral follicle count but not with metabolic parameters. However, SHBG and calculated free testosterone were associated with both ovarian ultrasound and metabolic parameters, such as BMI and insulin resistance.

          Conclusions

          Assessing SHBG and free testosterone is important in evaluating androgen excess in subfertile women with ovulatory dysfunction and suspected PCOS, as it reflects both ovarian and metabolic disturbances.

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          Most cited references19

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          Position statement: Utility, limitations, and pitfalls in measuring testosterone: an Endocrine Society position statement.

          William Rosner, Richard Auchus, Ricardo Azziz … (2007)
          The objective of the study was to evaluate the current state of clinical assays for total and free testosterone. The five participants were appointed by the Council of The Endocrine Society and charged with attaining the objective using published data and expert opinion. Data were gleaned from published sources via online databases (principally PubMed, Ovid MEDLINE, Google Scholar), the College of American Pathologists, and the clinical and laboratory experiences of the participants. The statement was an effort of the committee and was reviewed in detail by each member. The Council of The Endocrine Society reviewed a late draft and made specific recommendations. Laboratory proficiency testing should be based on the ability to measure accurately and precisely samples containing known concentrations of testosterone, not only on agreement with others using the same method. When such standardization is in place, normative values for total and free testosterone should be established for both genders and children, taking into account the many variables that influence serum testosterone concentration.
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            The polycystic ovary syndrome: a position statement from the European Society of Endocrinology.

            Gerard Conway, Didier Dewailly, Evanthia Diamanti-Kandarakis … (2014)
            Polycystic ovary syndrome (PCOS) is the most common ovarian disorder associated with androgen excess in women, which justifies the growing interest of endocrinologists. Great efforts have been made in the last 2 decades to define the syndrome. The presence of three different definitions for the diagnosis of PCOS reflects the phenotypic heterogeneity of the syndrome. Major criteria are required for the diagnosis, which in turn identifies different phenotypes according to the combination of different criteria. In addition, the relevant impact of metabolic issues, specifically insulin resistance and obesity, on the pathogenesis of PCOS, and the susceptibility to develop earlier than expected glucose intolerance states, including type 2 diabetes, has supported the notion that these aspects should be considered when defining the PCOS phenotype and planning potential therapeutic strategies in an affected subject. This paper offers a critical endocrine and European perspective on the debate on the definition of PCOS and summarises all major aspects related to aetiological factors, including early life events, potentially involved in the development of the disorder. Diagnostic tools of PCOS are also discussed, with emphasis on the laboratory evaluation of androgens and other potential biomarkers of ovarian and metabolic dysfunctions. We have also paid specific attention to the role of obesity, sleep disorders and neuropsychological aspects of PCOS and on the relevant pathogenetic aspects of cardiovascular risk factors. In addition, we have discussed how to target treatment choices based according to the phenotype and individual patient's needs. Finally, we have suggested potential areas of translational and clinical research for the future with specific emphasis on hormonal and metabolic aspects of PCOS.
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              PCOS according to the Rotterdam consensus criteria: Change in prevalence among WHO-II anovulation and association with metabolic factors.

              F Broekmans, Marinus Eijkemans, Erik Knauff … (2006)
              The current report aims to compare the prevalence of polycystic ovary syndrome (PCOS) diagnosed according to the new Rotterdam criteria (Rott-PCOS) versus the previous criteria as formulated by the National Institutes of Health (NIH) (NIH-PCOS) in women with normogonadotropic (WHO-II) anovulation and assess the frequency of obesity and related factors determined in these women. Cohort study based on large anovulation screening database. Two large tertiary referral centres for reproductive medicine. WHO-II normogonadotropic, anovulatory, infertility cases. WHO-II cases were extracted from the screening database and classified according to both the Rotterdam and NIH criteria for PCOS. Within these two classes, the prevalence of obesity, hyperglycaemia and insulin resistance was assessed and compared and their relation to the difference in diagnostic criteria applied was analysed. Prevalence of diagnosis PCOS in the WHO-II anovulation group. Prevalence of obesity, hyperglycaemia and insulin resistance in the two diagnostic classes. The Rott-PCOS group appeared to be more than 1.5 times larger than the group classified as NIH-PCOS (91 versus 55% of the WHO-II cohort). Especially, women with ovarian dysfunction and polycystic ovaries at ultrasound scan, but without hyperandrogenism, were added to the PCOS diagnostic group. The Rott-PCOS exhibited a lower frequency of obesity, hyperglycaemia and insulin resistance compared with the NIH-PCOS group. Obese women in the Rott-PCOS group without androgen excess had a different metabolic profile compared with obese women in the NIH-PCOS group, with lower rates of hyperglycaemia and hyperinsulinism, despite comparable distributions of body weight. The present findings indicate that with the new Rotterdam consensus criteria, oligo/anovulatory women with less severe metabolic derangement will be added to the heterogeneous group of women with PCOS.
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                Author and article information

                Contributors
                D. Vanderschueren:
                ORCID: http://orcid.org/0000-0003-1395-0104
                Journal
                Journal ID (nlm-ta): Int J Endocrinol
                Journal ID (iso-abbrev): Int J Endocrinol
                Journal ID (publisher-id): IJE
                Title: International Journal of Endocrinology
                Publisher: Hindawi
                ISSN (Print): 1687-8337
                ISSN (Electronic): 1687-8345
                Publication date Collection: 2018
                Publication date (Electronic): 10 September 2018
                Volume: 2018
                Electronic Location Identifier: 7956951
                Affiliations
                1Department of Chronic Diseases, Metabolism and Ageing (CHROMETA), Laboratory of Clinical and Experimental Endocrinology, KU Leuven, Leuven, Belgium
                2Department of Endocrinology, University Hospitals Leuven, Leuven, Belgium
                3Department of Laboratory Medicine, University Hospitals Leuven, Leuven, Belgium
                4Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium
                5Department of Cellular and Molecular Medicine, Laboratory of Molecular Endocrinology, KU Leuven, Leuven, Belgium
                6Department of Obstetrics and Gynecology, University Hospitals Leuven, Leuven, Belgium
                7Department of Reproductive Medicine, Antwerp University Hospital, Edegem, Belgium
                Author notes

                Academic Editor: Amerigo Vitagliano

                Author information
                http://orcid.org/0000-0002-1079-2860
                http://orcid.org/0000-0002-8676-7709
                http://orcid.org/0000-0003-4153-4757
                http://orcid.org/0000-0003-1395-0104
                Article
                DOI: 10.1155/2018/7956951
                PMC ID: 6151847
                PubMed ID: 30275830
                SO-VID: f10e9352-956e-4fdd-939e-f73f2b809784
                Copyright © Copyright © 2018 L. Antonio et al.
                License:

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 27 November 2017
                Date revision received : 8 February 2018
                Date accepted : 28 June 2018
                Funding
                Funded by: University Hospitals Leuven
                Funded by: University of Leuven
                Award ID: GOA/15/017
                Funded by: Fonds Wetenschappelijk Onderzoek
                Award ID: G085413N
                Categories
                Subject: Research Article

                ScienceOpen disciplines: Endocrinology & Diabetes
                Data availability:
                ScienceOpen disciplines: Endocrinology & Diabetes

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