Hyperandrogenemia in Polycystic Ovary Syndrome: Exploration of the Role of Free Testosterone and Androstenedione in Metabolic Phenotype

Lerchbaum, Elisabeth; Schwetz, Verena; Rabe, T.; Giuliani, Albrecht; Obermayer–Pietsch, Barbara

doi:10.1371/journal.pone.0108263

Cited by 87 publications

(76 citation statements)

References 40 publications

(51 reference statements)

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“…In fact, it is well know that insulin excess is able to stimulate theca cell steroidogenesis and reduces hepatic SHBG synthesis, thereby leading to hyperandrogenemia (8). This has been confirmed by a long list of studies showing a significant association between insulin and androgens, particularly testosterone and androstenedione (13,14,18). In addition, there is a general consensus that in most women with PCOS, a mild-tomoderate insulin resistance may be responsible for the high prevalence of the metabolic syndrome (39) and that insulin sensitizers, such as metformin, may improve total and free testosterone in these women (1,8).…”

Section: Severe Insulin-resistant Syndrome and Pcosmentioning

confidence: 91%

“…In fact, increasing evidence supports that androgen excess represents a constitutive biomarker of PCOS. As expected, an androgen profile rather than testosterone alone should be used, as documented by several recent studies (12,13,14,15,16,18). A fundamental prerequisite is represented by the fact that if different androgens are needed to fully define hyperandrogenemia in these women, it could be that different mechanisms may be involved in regulating the enzyme activity involved in the androgen production rate or in their metabolic clearance rate (18).…”

Section: Arguments In Favor Of the Definition Of Secondary Pcosmentioning

confidence: 96%

“…Several recent studies have shown that extremely accurate and sensitive technologies in the detection and analysis of steroids, such as liquid chromatography-tandem mass spectrometry (LC-MS/MS) (8), have significantly improved the definition of the androgenemic blood pattern in women with PCOS (11,12,13,14,15,16,17,18). These studies have clearly shown that a steroid profile, including not only testosterone blood levels but also androstenedione and the free androgen index (FAI), may optimize the diagnosis of hyperandrogemia in women with PCOS, therefore improving our understanding on the heterogeneity of its phenotypes.…”

Section: Arguments In Favor Of the Definition Of Secondary Pcosmentioning

confidence: 99%

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MANAGEMENT OF ENDOCRINE DISEASE: Secondary polycystic ovary syndrome: theoretical and practical aspects

Pasquali

Diamanti-Kandarakis

Gambineri

2016

European Journal of Endocrinology

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PCOS is a clinical heterogeneous entity of female androgen excess diagnosed by exclusion of other disorders responsible for androgen excess. The concept of secondary PCOS implies that there is a primary well-defined cause leading to the PCOS phenotype with underlying androgen overproduction, regardless of the origin. In these cases, we presume the term of 'secondary PCOS' could be used. In all these conditions, the potential complete recovery of the hyperandrogenemic state as well as the remission of the PCOS phenotype should follow the removal of the cause. If accepted, these concepts could help clinicians to perform in-depth investigations of the potential factors or disorders responsible for the development of these specific forms of secondary PCOS. Additionally, this could contribute to develop further research on factors and mechanisms involved in the development of the classic and the nonclassic PCOS phenotypes. Invited author's profileRenato Pasquali is full professor of Endocrinology & Metabolism and Director of the division of Endocrinology of the S.Orsola-Malpighi Hospital, Bologna, Italy. He also heads the School of Specialization in Endocrinology and Metabolism, University Alma Mater Studiorum of Bologna, Italy. He is a member of numerous national and international scientific societies and serves on the editorial boards of international journals. His scientific interests relate to (i) the pathophysiology and treatment of the polycystic ovary syndrome; (ii) the endocrinology of obesity (sex hormones, the hypothalamic-pituitary-adrenal axis, and the endocannabinoid system).

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Section: Severe Insulin-resistant Syndrome and Pcosmentioning

confidence: 91%

Section: Arguments In Favor Of the Definition Of Secondary Pcosmentioning

confidence: 96%

Section: Arguments In Favor Of the Definition Of Secondary Pcosmentioning

confidence: 99%

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MANAGEMENT OF ENDOCRINE DISEASE: Secondary polycystic ovary syndrome: theoretical and practical aspects

Pasquali

Diamanti-Kandarakis

Gambineri

2016

European Journal of Endocrinology

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“…They also reported a strong negative association between serum androstenedione and insulin sensitivity, and a high incidence of glucose intolerance correlating with the severity of the androgen phenotype. Interestingly, Lerchbaum et al (76) reported that elevated free testosterone, unlike isolated androstenedione elevation, was associated with an adverse metabolic phenotype.…”

Section: Alternative Approach: Measuring Androstenedionementioning

confidence: 99%

“…The combination of total testosterone, androstenedione and free testosterone provides good accuracy for diagnosis of PCOS and its hyperandrogenemic sub-phenotypes (76,77,78). However, application for predicting metabolic risk in PCOS needs further investigation (79).…”

Section: Alternative Approach: Measuring Androstenedionementioning

confidence: 99%

MANAGEMENT OF ENDOCRINE DISEASE Hyperandrogenic states in women: pitfalls in laboratory diagnosis

Pugeat

Plotton

Perrière

et al. 2018

European Journal of Endocrinology

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Measuring total testosterone level is the first-line approach in assessing androgen excess in women.The main pitfalls in measuring testosterone relate to its low concentration and to the structural similarity between circulating androgens and testosterone, requiring accurate techniques with high specificity and sensitivity. These goals can be achieved by immunoassay using a specific antitestosterone monoclonal antibody, ideally after an extraction step. Liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) will be commonly used for measuring testosterone, providing optimal accuracy with a low limit of detection. Yet, the pitfalls of these two techniques are well identified and must be recognized and systematically addressed. In general, laboratories using direct testosterone immunoassay and mass spectrometry need to operate within a quality framework and be actively engaged in external quality control processes and standardization, so as to ensure appropriate interpretation irrespective of the particular laboratory. Circulating testosterone is strongly bound to sex-hormone binding-globulin (SHBG), and SHBG levels are typically low in overweight hyperandrogenic patients. Thus, low SHBG may decrease circulating testosterone to normal values, which will mask androgen excess status. One way to avoid this pitfall, awaiting direct free-testosterone assays that are yet to be developed, is to measure SHBG and calculate free testosterone. A few other pitfalls will be discussed in this review, including those of adrenal androgen exploration, with the aim of helping clinicians to better handle laboratory investigation of androgen excess disorders in women.

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Role of androgen ratios in the prediction of the metabolic phenotype in polycystic ovary syndrome

Minooee

Tehrani

Tohidi

et al. 2017

Int J Gynecol Obstet

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Hyperandrogenemia in Polycystic Ovary Syndrome: Exploration of the Role of Free Testosterone and Androstenedione in Metabolic Phenotype

Cited by 87 publications

References 40 publications

MANAGEMENT OF ENDOCRINE DISEASE: Secondary polycystic ovary syndrome: theoretical and practical aspects

MANAGEMENT OF ENDOCRINE DISEASE: Secondary polycystic ovary syndrome: theoretical and practical aspects

MANAGEMENT OF ENDOCRINE DISEASE Hyperandrogenic states in women: pitfalls in laboratory diagnosis

Role of androgen ratios in the prediction of the metabolic phenotype in polycystic ovary syndrome

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