The Paradox Dividing Testosterone Deficiency Symptoms and Androgen Assays: A Closer Look at the Cellular and Molecular Mechanisms of Androgen Action

Abstract

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: 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.

International web survey shows high prevalence of symptomatic testosterone deficiency in men

“…However it has been found that the AMS scale can be used to measure and compare the health-related quality of life in those of less than 40 years of age on the basis of similar European normative values [16]. The surprisingly high prevalence of raised scores in the younger age groups may be due to the increasing impact of work stress in these age groups, which has been shown to decrease testosterone synthesis [17,18] and increase resistance to its action [19]. …”

“…The uniform and sustained relief of these symptoms given by testosterone treatment has been confirmed by the experience over more than 15 years in 1700 men in the UKAS treated predominantly on the basis of their symptoms rather than androgen levels [19]. …”

“…This can be explained by the concept of ‘androgen resistance’ [19]. 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.…”

Measurement of testosterone in the diagnosis of hypogonadism in the ageing male

“…More controversially Carruthers 35 suggests that the symptoms are more important than the biochemistry suggesting that a male may be ‘hypogonadal’ at the tissue level while having a normal T level. Reduced arterial flow and pre‐DHT receptor events are suggested 36 . Proper clinical trails are required to support these suggestions.…”

“…Reduced arterial flow and pre-DHT receptor events are suggested. 36 Proper clinical trails are required to support these suggestions.…”