Endocrine Abstracts

The Androgen receptor (AR) CAG repeat polymorphism in exon 1 within human populations encodes for a polyglutamine stretch which varies between 9 to 35 repeats. The greater the number of CAG repeats the less sensitive the receptor in relation to biological functions. It is known that lesser the AR sensitivity the higher the circulating testosterone levels are required to provide normal AR stimulation. Notably CAG repeat numbers are positively associated with LH, FSH, waist circumference, % body fat, leptin and insulin. In clinical practise some men with symptoms of hypogonadism may not be diagnosed or if diagnosed may not respond to testosterone therapy. The aim of this study was to examine the relationship between AR sensitivity, testosterone (total, free, bioavailable) and symptom response between men who were treatment responders vs non-responders. Hypogonadal men (n=32), diagnosed by clinical guideline criteria for testosterone deficiency were treated with transdermal gel and were assessed at 3, 6 and 12 months. Symptoms were assessed using the validated AMS (Aging Male Symptom) score which was correlated with TT, calculated freeT and BioT / CAG ratios. At 6 months the study cohort was divided into responders (AMS <33% improvement) and non-responders by AMS score (>33% improvement). Non-responders had ARCAG repeats mean 21.8+3.9 v responders 18.7+2.7 (P=0.03). ARCAG repeats showed significant potential (P= 0.028) in differentiating non-responders from responders to treatment with sensitivity of 95.2%, specificity of 50%. No correlation was found in relation to TT, freeT or BioT or T/CAG repeat ratios. This study showed that non-responders to treatment had significantly higher numbers of ARCAG repeats i.e. more insensitive AR. This study findings may indicate the need for higher post-treatment T levels in non-responders and / or men with a higher number of the ARCAG repeats >22. There is a clinical benefit of assessing the ARCAG.