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Cited by 30Ovarian function and disordersHormonal and reproductive studiesAdrenal Hormones and Disorders

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

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Antonio, L., Pauwels, S., Laurent, M. R., Vanschoubroeck, D., Jans, I., Billen, J., Claessens, F., Decallonne, B. +3 more·2018·International Journal of Endocrinology
DOI 10.1155/2018/7956951PMC PMC6151847
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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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  • In PCOS and obesity, the fall in SHBG is unable to buffer rising free T concentration, leading to androgen excess and clinical consequences.

    “In PCOS and obesity setting, this fall in SHBG is unable to buffer rising free T concentration, leading to androgen excess and clinical consequences in these women [197].”

    From Role of sex hormone-binding globulin in the free hormone hypothesis and the relevance of free testosterone in androgen physiology (2022) · cites this paper as [197]

    The Discussion says that as BMI rises and SHBG falls, its buffering capacity is breached, leading to higher free testosterone and androgen excess. It says clinical consequences are likely or possible, rather than establishing that they occur; the cited discussion also concerns women with subfertility and oligomenorrhea, not all women with PCOS. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • Androgen excess disturbs the hypothalamic-pituitary-ovarian axis, hindering cyclic production of estradiol and progesterone, causing oligomenorrhea and ovulatory dysfunction.

    “Favoring LH over FSH synthesis in the pituitary gland, this disturbance of the hypothalamic–pituitary–ovarian axis by androgen excess hinders cyclic production of estradiol and progesterone, causing oligomenorrhea and ovulatory dysfunction [197, 240].”

    From Role of sex hormone-binding globulin in the free hormone hypothesis and the relevance of free testosterone in androgen physiology (2022) · cites this paper as [197]

    The Discussion links androgen excess to disrupted hypothalamic–pituitary–ovarian function, increased LH relative to FSH, and hampered cyclic estradiol and progesterone production. It says androgen excess *can* cause this disruption and that oligomenorrhea and ovulatory dysfunction *may* be early signs; the citing sentence presents the causal sequence more definitively. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • In oligomenorrheic subfertile women with suspected PCOS, total T and calculated free T correlate closely with ovarian volume and antral follicle count.

    “For example, in oligomenorrheic subfertile women with a suspicion of PCOS, total T as well as calculated free T correlated closely with ovarian volume and antral follicle count.”

    From Role of sex hormone-binding globulin in the free hormone hypothesis and the relevance of free testosterone in androgen physiology (2022) · cites this paper as [197]

  • In the evaluation of androgen excess in women suspected with PCOS, it is important to evaluate both free T and SHBG, as they reflect both metabolic and ovarian disturbances associated with this disease.

    “In the evaluation of androgen excess in women suspected with PCOS, it is thus important to evaluate both free T and SHBG, as they reflect both metabolic and ovarian disturbances associated with this disease [197].”

    From Role of sex hormone-binding globulin in the free hormone hypothesis and the relevance of free testosterone in androgen physiology (2022) · cites this paper as [197]

  • Free T positively correlates with LH and the LH/FSH ratio, independent of BMI.

    “Additionally, free T positively correlated with LH as well as the LH/follicle stimulating hormone (FSH)-ratio, independent of BMI.”

    From Role of sex hormone-binding globulin in the free hormone hypothesis and the relevance of free testosterone in androgen physiology (2022) · cites this paper as [197]

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Authors
Antonio, L., Pauwels, S., Laurent, M. R., Vanschoubroeck, D., Jans, I., Billen, J., Claessens, F., Decallonne, B., De Neubourg, D., Vermeersch, P., & Vanderschueren, D.
Affiliations
  • Universitair Ziekenhuis Leuven (BE)
  • KU Leuven (BE)
  • Department of Reproductive Medicine, Antwerp University Hospital, Edegem, Belgium
Corresponding author
Vanderschueren, D.
ORCID
Venue
International Journal of Endocrinology
Publisher
Wiley
Published
2018-09-10
Volume
2018
Pages
1-8
ISSN
  • 1687-8337 (ISSN-L)
  • 1687-8345
DOI
10.1155/2018/7956951
PMC
PMC6151847
OpenAlex
W2892306803
Cited by
30
References
8
Citations by year
2026: 4 · 2025: 2 · 2024: 2 · 2023: 5 · 2022: 5 · 2021: 7 · 2020: 3 · 2019: 1 · 2018: 1
FWCI
3.22
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Endocrinology (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Lirias (submittedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • University Hospitals Leuven (GOA/15/017, G085413N)
  • University of Leuven (GOA/15/017, G085413N)
  • Fonds Wetenschappelijk Onderzoek (GOA/15/017, G085413N)
Topics
  • Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
Keywords
free testosterone, polycystic ovary syndrome, oligomenorrhea, subfertility, sex hormone-binding globulin, hyperandrogenism, insulin resistance, antral follicle count, ovarian volume, body mass index, ovulatory dysfunction

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