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].

Tsampoukas 等人的综合综述概述了当代男科的一个令人担忧的现实：对于睾酮缺乏症（testosterone deficiciecy， TD）的定义和男性性腺功能减退症的诊断/治疗缺乏共识[1]。他们对九项主要指南的分析揭示了差异，这些差异超出了单纯的阈值差异，可能会影响临床决策。这些变化凸显了未来解决这些问题的必要性。在这方面，作者确定了从“男性性腺功能减退症”到“睾酮缺乏症”再到“功能性性腺功能减退症”的术语不一致。因此，这种语言异质性反映了关于低睾酮的病理生理学基础的潜在分歧。这反映了对临床综合征的不同看法。例如，欧洲泌尿外科协会（European Association of Urology， EAU）指南强调对睾丸功能障碍的更全面定义，包括雄激素性衰竭和生精性衰竭[2]。相比之下，美国泌尿外科协会（American Urological Association， AUA）的指南主要关注有症状的 TD[2,3]。欧洲男科学会引入“功能性性腺功能减退症”增加了另一层复杂性，试图区分可逆抑制和不可逆器质性病因[4,5]。在此背景下，这种性腺功能减退症的分类系统缺乏普遍接受和明确的管理策略。

也许最令人担忧的是诊断生化临界值的可变性。总睾酮阈值已被确定为 8 nmol/L （231 ng/dL） 至 12 nmol/L （346 ng/dL）;这不可避免地会产生一个“灰色地带”，影响到不可忽视的比例接受 TD 评估的男性 [2， 3， 6]。这种变异不能仅仅归因于测定差异或种群特征;相反，它反映了对性腺功能减退症状出现的总睾酮水平的不确定性。保险提供商和监管机构对于使用什么下限来承保规定的睾酮治疗存在分歧，有些要求水平低于 300 ng/dL，而另一些则使用 250 ng/dL 作为阈值。作者正确地强调，虽然大多数社会都趋同于游离睾酮临界值在 220-225 pmol/L 左右，但游离睾酮的作用仍然存在争议。异质性是惊人的：AUA 指南没有提及游离睾酮测量，而内分泌学会建议在总睾酮处于临界值时进行游离睾酮评估 [3， 6]。EAU 和英国性医学学会主张在总睾酮在 8-12 nmol/L 之间，特别是当怀疑 SHBG 异常时，应进行免费睾酮测量[2,7]。国际性医学学会同样支持对临界病例进行游离睾酮评估，而意大利学会（Società Italiana di Andrologia e Medicina della Sessualità和 Società Italiana Endocrinologia）正式将游离睾酮纳入其诊断算法[8]。 值得注意的是，内分泌学会对游离睾酮测量的怀疑与其他学会在临界病例的这一参数上形成鲜明对比[9]。