The paradox dividing testosterone deficiency symptoms and androgen assays: A closer look at the cellular and molecular mechanisms of androgen action
The paradox dividing testosterone deficiency symptoms and androgen assays: A closer look at the cellular and molecular mechanisms of androgen action
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DOI：
10.1111/j.1743-6109.2007.00721.x
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发表时间：
2008-04-01
影响因子：
3.5
通讯作者：
Carruthers, Malcolm
中科院分区：
文献类型：
--
作者：
Carruthers, Malcolm
导论.成年男性睾酮缺乏综合征的诊断和治疗的核心是一个显著的悖论，即特征性症状与血清雄激素水平之间的相关性非常差。由于雄激素缺乏症可能与严重的前列腺疾病以及冠心病、糖尿病和代谢综合征等多种疾病相关，因此本研究旨在提出一种基于证据的工作假设，以解决这一令人困惑的临床矛盾。在睾酮缺乏综合征的可能机制进行了审查，并建立了一个假说来解释这个悖论和相关的问题，在诊断和临床管理雄激素缺乏症的文献综述的基础上。雄激素缺乏症可能出现的机制进行了研究，在五个不同的水平：1。雄激素合成或调节受损。增加雄激素结合。3.降低组织反应性。4.雄激素受体活性降低。转录和转录受损。与成熟型糖尿病中的胰岛素一样，可能存在对体内多个水平的雄激素作用的生产不足和不同程度的抵抗，这些因素随着年龄的增长、不良的生活方式、其他疾病过程和广泛的药物治疗而逐渐恶化。使用这个模型，雄激素缺乏症可以被重新定义为雄激素或其代谢物的绝对或相对缺乏，根据个人在他生命中的那个时候的需要。这一假说提出的考虑因素影响雄激素缺乏状态的病因学、术语学、诊断和治疗的重要方式。
Introduction. Central to the diagnosis and treatment of testosterone deficiency syndrome in the adult male is the remarkable paradox that there is a very poor correlation between the characteristic symptoms and levels of serum androgens.Aim. Because androgen deficiency can be associated with severe symptomatology, as well as diverse conditions such as coronary heart disease, diabetes, and metabolic syndrome, the aim was to present an evidence-based working hypothesis to resolve this confusing clinical paradox.Methods. A review of the possible mechanisms in testosterone deficiency syndrome was carried out, and a hypothesis to explain this paradox and associated problems in the diagnosis and clinical management of androgen deficiency was established on the basis of a review of the literature.Main Outcome Measures. The mechanisms by which androgen deficiency could arise were studied at five different levels:1. Impaired androgen synthesis or regulation.2. Increased androgen binding.3. Reduced tissue responsiveness.4. Decreased androgen receptor activity.5. Impaired transcription and translation.Results. As with insulin in maturity onset diabetes mellitus, there can be both insufficient production and variable degrees of resistance to the action of androgens operating at several levels in the body simultaneously, with these factors becoming progressively worse with aging, adverse lifestyle, other disease processes, and a wide range of medications.Conclusions. Using this model, androgen deficiency can be redefined as an absolute or relative deficiency of androgens or their metabolites according to the needs of that individual at that time in his life. There are important ways in which the considerations raised by this hypothesis affect the etiology, terminology, diagnosis, and treatment of androgen-deficient states.