(211) EFFECT OF ANDROGEN RECEPTOR POLYMORPHISM ON HYPOGONADISM SEVERITY

Abstract Introduction The preferred treatment for hypogonadism, testosterone replacement therapy (TRT), has a varying efficacy that is currently not understood. This observation may be explained by polymorphism of the androgen receptor (AR), a ligand-binding transcription factor whose polyglutamine tract length affects various health conditions and androgen sensitivity. It has been theorized that this polymorphism may also affect severity of hypogonadism. Objective This study sought to determine a correlation between hypogonadism severity and number of CAG trinucleotide repeats in the AR gene. Methods 17 males presenting to Baylor College of Medicine with symptoms of hypogonadism were recruited for this study. PHQ-9 and IIEF-15 surveys were taken upon initial visit. Patients’ testosterone (T) levels were measured before starting TRT. CAG repeat length was determined via polymerase chain reaction (PCR) followed by Sanger sequencing. Linear regression and nonparametric Wilcoxon testing (RStudio) were performed to test for a correlation between measured parameters. Results Average number of CAG repeats found was 23 ± 3.1, which is within the normal range as described by current literature. No correlation was found between: PHQ-9 score and CAG repeat length (p = 0.8543), PHQ-9 score and baseline (endogenous) T levels (p = 0.1680), IIEF-15 score and CAG repeat length (p = 0.4650), IIEF-15 score and baseline T levels (p = 0.9301), [EF] subscore and CAG repeat length (p = 0.5404), [EF] subscore and baseline T levels (p = 0.9159), or T levels and CAG repeat length (p = 0.3624). Half of the patients (n = 8) had [EF] subscores <14, indicating erectile dysfunction. However, Wilcoxon testing reveals that this difference is not significantly less than the cutoff (p = 0.4375), a result likely due to the small sample size. These findings are consistent with the literature, which suggests that a correlation between CAG repeat length and erectile function only exists in eugonadal men. Conclusions These data suggest that CAG repeat length may not serve as an accurate measure of hypogonadism severity. Additionally, baseline T levels did not significantly correlate with symptom severity in this small population. More research with a larger sample size is needed to determine the relationship between CAG repeat length, hypogonadism, and TRT efficacy. Additionally, genotyping of the polyglycine tract, another repeat region downstream of the polyglutamine tract, is ongoing, which may reveal more about this novel approach to understanding the mechanism behind TRT. Disclosure No.