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<p>The advent of liquid chromatography&#xa0;- mass spectrometry (LC-MS/MS) resulted in consolidating the importance of accurate measurements of steroid hormones in the diagnosis and management of female hyperandrogenisms. Moreover, this technique is boosting a renewed interest in non-canonical steroid pathways. Modern LC-MS/MS panels, which include a large number of steroids of different classes, offer great potential for the characterisation of female hyperandrogenisms. Hopefully, monitoring several pathways at the same time will help clarify the obscure aspects of various forms of hyperandrogenism as well as improving their diagnosis. We are facing an evolution of the current diagnostic paradigm, based on the evaluation of a few hormones interpreted with respect to rigid and unstandardised threshold values, in favour of a system vision more suitable for the characterisation of complex diseases with a high degree of phenotypic heterogeneity, in line with the modern concept of precision medicine. Other important applications of multisteroid LC-MS/MS panels involve the characterisation of drugs that act on steroidogenesis, and sports medicine. In recent years, 11-oxygenated-C19 androgens are attracting vast attention. Although the relevance of these androgens in some deficits of steroidogenesis is evident, data obtained so far do not show a clear link between 11-oxygenated-C19 androgens, clinical hyperandrogenism and dysmetabolism in other contexts, such as PCOS. Further studies in large and well characterised populations are required to unravel the role of non-canonical pathways in female pathophysiology, aided by the use of functional tests and by the definition of robust reference ranges. In particular, there is a need to clarify the trajectories of steroid flow through the different pathways during the complex period of sexual maturation, in order to establish early biomarkers of risk of premature adrenarche as well as of evolution towards hyperandrogenism and PCOS. These studies are also necessary to validate effective markers that would allow for recognition of non-classical and heterozygous forms of adrenal steroidogenesis deficits. Future evidence could, therefore, offer new pharmacological targets for prevention and control of hyperandrogenic diseases and dysmetabolic evolutions.</p>

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Lo steroidoma circolante negli iperandrogenismi femminili: il ruolo della cromatografia liquida abbinata a spettrometria di massa

  • 期刊论文

  • 发表日期：

    2025年2月5日

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  • Flaminia Fanelli,
  • Uberto Pagotto,
  • Alessandra Gambineri

摘要

The advent of liquid chromatography - mass spectrometry (LC-MS/MS) resulted in consolidating the importance of accurate measurements of steroid hormones in the diagnosis and management of female hyperandrogenisms. Moreover, this technique is boosting a renewed interest in non-canonical steroid pathways. Modern LC-MS/MS panels, which include a large number of steroids of different classes, offer great potential for the characterisation of female hyperandrogenisms. Hopefully, monitoring several pathways at the same time will help clarify the obscure aspects of various forms of hyperandrogenism as well as improving their diagnosis. We are facing an evolution of the current diagnostic paradigm, based on the evaluation of a few hormones interpreted with respect to rigid and unstandardised threshold values, in favour of a system vision more suitable for the characterisation of complex diseases with a high degree of phenotypic heterogeneity, in line with the modern concept of precision medicine. Other important applications of multisteroid LC-MS/MS panels involve the characterisation of drugs that act on steroidogenesis, and sports medicine. In recent years, 11-oxygenated-C19 androgens are attracting vast attention. Although the relevance of these androgens in some deficits of steroidogenesis is evident, data obtained so far do not show a clear link between 11-oxygenated-C19 androgens, clinical hyperandrogenism and dysmetabolism in other contexts, such as PCOS. Further studies in large and well characterised populations are required to unravel the role of non-canonical pathways in female pathophysiology, aided by the use of functional tests and by the definition of robust reference ranges. In particular, there is a need to clarify the trajectories of steroid flow through the different pathways during the complex period of sexual maturation, in order to establish early biomarkers of risk of premature adrenarche as well as of evolution towards hyperandrogenism and PCOS. These studies are also necessary to validate effective markers that would allow for recognition of non-classical and heterozygous forms of adrenal steroidogenesis deficits. Future evidence could, therefore, offer new pharmacological targets for prevention and control of hyperandrogenic diseases and dysmetabolic evolutions.