The Impact of Androgen Receptor CAG Repeat Polymorphism on Andropausal Symptoms in Different Serum Testosterone Levels

Introduction. In addition to a depletion of androgen, attenuated action of androgen receptor (AR) might also contribute to andropausal symptoms. Aim. To evaluate the interaction of AR cytosine adenine guanine (CAG) repeat polymorphism and serum testosterone levels and their effect on andropausal symptoms in aging Taiwanese men. Methods. From August 2007 to April 2008, a free health screening for men older than 40 years was conducted by a medical center in Kaohsiung City, Taiwan. All participants received physical examination, answered questionnaires to collect their demographic information and medical histories, completed the Androgen Deficiency in the Aging Male (ADAM) questionnaire, and provided 20-cm³ whole blood samples for biochemical and genetic evaluation. Main Outcome Measures. The ADAM questionnaire was used to evaluate andropausal symptoms. Serum albumin, total testosterone (TT), and sex hormone-binding globulin levels were measured. Free testosterone level was calculated. AR gene CAG repeat polymorphism was determined by direct sequencing. Results. Seven hundred two men with the mean age of 57.2±6.5 years were included. There was no significant association between TT levels and the distribution of AR CAG repeat polymorphism. When TT levels were above 340ng/dL, subjects with AR CAG repeat lengths ≧25 showed significantly higher risk of developing andropausal symptoms, as compared with those with AR CAG repeat lengths ≦22 (P=0.006), but this was not observed when TT levels were 340ng/dL or below. Age and number of comorbidities were also independent risk factors for andropausal symptoms. Conclusion. In subjects with normal TT concentration, those with longer AR CAG repeat lengths have a higher risk of developing andropausal symptoms. Age and number of comorbidities can also influence the appearance of andropausal symptoms. In clinical practice, a multifactorial approach to evaluate andropausal symptoms and the interactions between those risk factors is suggested.