Endocrine Abstracts (2009) 20 S4.2

Pharmacogenetics of androgen action

D Canale, C Caglieresi, S Gavioli, A Moscatelli, E Martino & P Vitti

Department of Endocrinology, University of Pisa Medical School and Hospitals, Pisa, Italy.

Hypogonadism is still a poorly-defined clinical entity. Recently approved and published guidelines to diagnosis and treatment of hypogonadism claim the necessity of accompanying biochemical thresholds with clinical symptoms and monitoring under treatment a specific aspect of the ‘wide spectrum’ hypogonadism (libido, erection, bone mass, muscle strength and so on). This is due both to different levels of thresholds for different tissues and to individual variability.

Most part of interindividual variability relies on androgen receptor (AR) polymorphism linked to variations in the length of CAG repeats (CAGr) in exon 1. Many studies have shown that the longer the CAGr the weaker the androgen action and viceversa. This is true both for endogenous and exogenous androgens. In presence of similar testosterone (T) plasma levels, the final phenotypic androgenic effect or ‘androgenicity’ is mainly due to CAGr length. This is particularly relevant when exogenous T is administered. Data are emerging that androgen replacement treatment (ART) should be tailored on AR polymorphism to balance between clinical benefits and risks. Moreover, specific patient categories, such as obese men or patients with metabolic syndrome, represent clinical conditions that should deserve particular attention during ART, since shorter CAGr could amplify a clinical effect, such as polycitemia or sleep apnea.

It is rather strange to believe nowadays that strict diagnostic criteria and strict scheduled treatments could apply to all the spectrum of hypogonadal patients. Pharmacogenetically tailored diagnosis and treatment should be considered in this field of medicine.

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