madman
Super Moderator
Abstract
INTRODUCTION AND OBJECTIVES:
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 the severity of hypogonadism and associated symptoms like erectile dysfunction. This study sought to establish a correlation between hypogonadism severity, TRT efficacy, and number of CAG trinucleotide repeats in the AR gene.METHODS:
164 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’ baseline and follow-up testosterone (T) levels were measured before and after starting TRT, respectively. CAG repeat length was determined via polymerase chain reaction (PCR) followed by Sanger sequencing. Linear regression and t–test (RStudio) were performed.RESULTS:
Average patient age was 52. Average number of CAG repeats found was 22 ± 3.1, which is within the normal range as described by current literature. Patients whose T levels superseded 700 ng/dL following TRT demonstrated a higher average CAG repeat length than those who did not (p=0.05). A very loose, but statistically significant correlation (R2=0.03, p = 0.04) was found between T levels following TRT and CAG repeat number (Figure 1). Additionally, hypogonadal patients with a baseline T value above 300 ng/dL demonstrated a higher average CAG repeat length than those below 300, though this did not reach significance (p=0.06). No correlation was found between: PHQ-9 score and CAG repeat length (p=0.61), IIEF-15 score and CAG repeat length (p=0.89), [EF] subscore and CAG repeat length (p=0.64), or baseline T levels and CAG repeat length (p=0.91).CONCLUSIONS:
These data suggest that CAG repeat length may serve as an accurate measure of TRT efficacy and hypogonadism severity. Patients with longer CAG repeat lengths may, therefore, exhibit hypogonadal symptoms despite seemingly eugonadal T levels and require more exogenous T to effectively treat symptoms. More research with a larger sample size and further analysis is needed to fully explore the relationship between CAG repeat length and hypogonadism.
