Endocrine Abstracts

In addition to symptoms of androgen deficiency induced by low serum testosterone concentrations (i.e. classical hypogonadism), also variable phenotypes of androgen insensitivity exist in humans, mainly owing to defective, mutated androgen receptors. A more subtle modulation of androgen effects has been related to the CAG repeat polymorphism (CAGn) in exon 1 of the androgen receptor gene: in vitro, transcription of androgen-dependent target genes is attenuated with increasing length of triplets. As a clinical entity, the CAG repeat polymorphism is, in healthy males, compensated for by an increased release of LH and, hence, testosterone. In men with an affected hypothalamic–pituitary–gonadal signal chain, however, it can relate to variations of androgenicity in (apparantly) eugonadal men in various tissues and psychological traits: the longer the CAGn, the less prominent is the androgen effect when individuals with similar testosterone concentrations are compared. A strictly defined threshold to hypogonadism might then be replaced by a continuum originating fom genetics, hormone concentrations as well as symptom specificity. In addition, effects of externally applied testosterone can be markedly influenced by the CAGn and respective pharmacogenetic implications are likely influence indications as well as modalities of testosterone treatment of hypogonadal men.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.