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Comment on: Variations in diagnostic criteria for male hypogonadism: is there a need for standardizing specialist society guidelines?

International Journal of Impotence Research (2025)Cite this article

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The comprehensive review by Tsampoukas et al., outlines a concerning reality in contemporary andrology: the absence of consensus regarding the definition of testosterone deficiency (TD) and male hypogonadism diagnosis/management [1]. Their analysis of nine major guidelines reveals discrepancies that extend beyond mere threshold differences, potentially affecting clinical decision-making. These variations highlight the need to address these issues in the future. In this regard, the authors identified terminological inconsistencies ranging from “male hypogonadism” to “testosterone deficiency” to “functional hypogonadism”. As such, this linguistic heterogeneity reflects potential disagreements about the pathophysiological basis of the low testosterone. This reflects varying perspectives on the clinical syndrome. For instance, the European Association of Urology (EAU) guidelines emphasize a more comprehensive definition of testicular dysfunction, encompassing both androgenic and spermatogenic failure [2]. In contrast, the American Urological Association (AUA) guidelines focus mainly on symptomatic TD [2, 3]. The introduction of “functional hypogonadism” by the European Academy of Andrology adds another layer of complexity, attempting to distinguish reversible suppression from irreversible organic etiology [4, 5]. In this context, this classification system of hypogonadism lacks universal acceptance and clear management strategies.

Perhaps most concerning is the variability in biochemical cutoffs for diagnosis. Total testosterone thresholds have been identified to range from 8 nmol/L (231 ng/dL) to 12 nmol/L (346 ng/dL); this inevitably creates a “gray zone” that affects a non-negligible proportion of men evaluated for TD [2, 3, 6]. This variation cannot be attributed solely to assay differences or population characteristics; rather, it reflects uncertainty about the total testosterone level below which symptoms of hypogonadism manifest. Insurance providers and regulatory agencies disagree on what lower limit to use to cover prescribed testosterone therapy, with some requiring levels below 300 ng/dL while others use 250 ng/dL as their threshold. The authors correctly highlight that while most societies converge on free testosterone cutoffs around 220–225 pmol/L, the role of free testosterone remains contentious. The heterogeneity is striking: the AUA guidelines make no mention of free testosterone measurements, while the Endocrine Society recommends free testosterone assessment when total testosterone is borderline [3, 6]. The EAU and British Society for Sexual Medicine advocate for free testosterone measurement in cases where total testosterone falls between 8 and 12 nmol/L, particularly when SHBG abnormalities are suspected [2, 7]. The International Society for Sexual Medicine similarly supports free testosterone evaluation for borderline cases, whereas the Italian societies (Società Italiana di Andrologia e Medicina della Sessualità and Società Italiana Endocrinologia) formally incorporate free testosterone into their diagnostic algorithm [8]. Notably, the Society for Endocrinology’s skepticism about free testosterone measurements contrasts with other societies on this parameter for borderline cases [9].

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References

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Authors and Affiliations

  1. Department of Urology, Vita-Salute San Raffaele University, Milan, Italy

    Edoardo Pozzi

  2. Division of Experimental Oncology, Unit of Urology, Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy

    Edoardo Pozzi

  3. Jumeirah American Clinic, Dubai, UAE

    Ranjith Ramasamy

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  1. Edoardo Pozzi
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  2. Ranjith Ramasamy
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Conception and design: EP and RR. Acquisition of data: EP and RR. Analysis and interpretation of data: EP and RR. Drafting of the manuscript: EP and RR. Critical revision of the manuscript for important intellectual content: EP and RR.

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Correspondence to Ranjith Ramasamy.

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EP is currently an Associate Editor for the International Journal of Impotence Research.

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Pozzi, E., Ramasamy, R. Comment on: Variations in diagnostic criteria for male hypogonadism: is there a need for standardizing specialist society guidelines?. Int J Impot Res (2025). https://doi.org/10.1038/s41443-025-01164-w

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