madman
Super Moderator
* The particular threshold of 700 ng/dL chosen for this study demonstrated the greatest, most significant difference in CAG repeat length between the two groups.
* In the cohort with complete follow-up data (n=75), patients whose testosterone levels superseded 700 ng/dL following therapy demonstrated a higher average CAG repeat length (22.5 codons) than those who did not (21.4 codons), though this result did not reach significance (P=0.11) (Table 2).
Figure 2 Final testosterone levels loosely correlate with CAG repeat length (R2=0.0631, P=0.02). Gray shading denotes 95% confidence interval. T, testosterone; TRT, testosterone replacement therapy.
Figure 1 CAG repeat distribution among hypogonadal patients. The average number was 21.7±3.1 codons, and the range was 11–29 codons.
Table 2 Mean CAG repeat lengths of groups divided by testosterone levels
* This study sought to compare the CAG repeat length of patients undergoing TRT to the treatment’s efficacy. Of the 162 patients, the average number of CAG repeats found was 21.7±3.1 codons (Figure 1), which falls within the typical range of 10–36 codons.
* In the cohort with complete follow-up data (n=75), patients whose testosterone levels superseded 700 ng/dL following therapy demonstrated a higher average CAG repeat length (22.5 codons) than those who did not (21.4 codons), though this result did not reach significance (P=0.11) (Table 2).
* The data from this cohort of 162 hypogonadal males suggest that there exists a relationship between CAG repeat length and hypogonadism severity. Current AUA guidelines denote 300 ng/dL as the serum testosterone cutoff for diagnosis of hypogonadism (20), but clinical data demonstrate that this criterion fails to account for a subset of the population who experiences hypogonadal symptoms despite serum testosterone levels exceeding the 300 ng/dL threshold. The data from this study provide a plausible explanation for why this subset exists. Hypogonadal males with baseline testosterone levels greater than 300 ng/dL demonstrated a significantly higher average CAG repeat length (22.1 codons) than those below 300 ng/dL (20.9 codons) (P=0.02). Previous research has demonstrated that CAG repeat length inversely correlates with the AR’s transcriptional activity (19). Therefore, these data suggest that males with longer CAG repeat regions exhibit a higher androgen insensitivity that manifests in hypogonadal symptoms at higher testosterone level.
* Additionally, patients with final testosterone levels exceeding 700 ng/dL following therapy demonstrated a higher average CAG repeat length (22.5 codons) than those who did not (21.4 codons) (P=0.11). It should also be noted that, in an earlier cohort (n=44), the difference between those who required testosterone levels exceeding 700 ng/dL to achieve symptomatic relief and those who did not (23.9 vs. 21.8 codons) was significant (P=0.02) (23). These data complicate the aforementioned notion that alleviation of hypogonadal symptoms can be categorized by universal thresholds, such as 600 ng/dL to fully improve symptoms of sexual dysfunction (21). Rather, these data demonstrate that supplementing testosterone past 700 ng/dL is necessary for some patients to achieve meaningful symptomatic relief. The particular threshold of 700 ng/dL chosen for this study demonstrated the greatest, most significant difference in CAG repeat length between the two groups. Therefore, further research should seek to more accurately determine where the cut-off lies and how CAG repeat length may be useful as a predictor for each patient’s ideal testosterone levels to achieve symptomatic relief.
Conclusions
Based on the results of this study, increased CAG repeat length correlates with symptoms of hypogonadism at serum testosterone levels exceeding 300 ng/dL. When used as a predictor alongside diabetes mellitus type 2 and ED, CAG repeat length demonstrates a significant linear correlation with serum testosterone levels needed for symptomatic relief. Therefore, providers should consider usage of CAG repeat length alongside patient reported symptoms when creating a treatment plan for hypogonadism.
* In the cohort with complete follow-up data (n=75), patients whose testosterone levels superseded 700 ng/dL following therapy demonstrated a higher average CAG repeat length (22.5 codons) than those who did not (21.4 codons), though this result did not reach significance (P=0.11) (Table 2).
Figure 2 Final testosterone levels loosely correlate with CAG repeat length (R2=0.0631, P=0.02). Gray shading denotes 95% confidence interval. T, testosterone; TRT, testosterone replacement therapy.
Figure 1 CAG repeat distribution among hypogonadal patients. The average number was 21.7±3.1 codons, and the range was 11–29 codons.
Table 2 Mean CAG repeat lengths of groups divided by testosterone levels
* This study sought to compare the CAG repeat length of patients undergoing TRT to the treatment’s efficacy. Of the 162 patients, the average number of CAG repeats found was 21.7±3.1 codons (Figure 1), which falls within the typical range of 10–36 codons.
* In the cohort with complete follow-up data (n=75), patients whose testosterone levels superseded 700 ng/dL following therapy demonstrated a higher average CAG repeat length (22.5 codons) than those who did not (21.4 codons), though this result did not reach significance (P=0.11) (Table 2).
* The data from this cohort of 162 hypogonadal males suggest that there exists a relationship between CAG repeat length and hypogonadism severity. Current AUA guidelines denote 300 ng/dL as the serum testosterone cutoff for diagnosis of hypogonadism (20), but clinical data demonstrate that this criterion fails to account for a subset of the population who experiences hypogonadal symptoms despite serum testosterone levels exceeding the 300 ng/dL threshold. The data from this study provide a plausible explanation for why this subset exists. Hypogonadal males with baseline testosterone levels greater than 300 ng/dL demonstrated a significantly higher average CAG repeat length (22.1 codons) than those below 300 ng/dL (20.9 codons) (P=0.02). Previous research has demonstrated that CAG repeat length inversely correlates with the AR’s transcriptional activity (19). Therefore, these data suggest that males with longer CAG repeat regions exhibit a higher androgen insensitivity that manifests in hypogonadal symptoms at higher testosterone level.
* Additionally, patients with final testosterone levels exceeding 700 ng/dL following therapy demonstrated a higher average CAG repeat length (22.5 codons) than those who did not (21.4 codons) (P=0.11). It should also be noted that, in an earlier cohort (n=44), the difference between those who required testosterone levels exceeding 700 ng/dL to achieve symptomatic relief and those who did not (23.9 vs. 21.8 codons) was significant (P=0.02) (23). These data complicate the aforementioned notion that alleviation of hypogonadal symptoms can be categorized by universal thresholds, such as 600 ng/dL to fully improve symptoms of sexual dysfunction (21). Rather, these data demonstrate that supplementing testosterone past 700 ng/dL is necessary for some patients to achieve meaningful symptomatic relief. The particular threshold of 700 ng/dL chosen for this study demonstrated the greatest, most significant difference in CAG repeat length between the two groups. Therefore, further research should seek to more accurately determine where the cut-off lies and how CAG repeat length may be useful as a predictor for each patient’s ideal testosterone levels to achieve symptomatic relief.
Conclusions
Based on the results of this study, increased CAG repeat length correlates with symptoms of hypogonadism at serum testosterone levels exceeding 300 ng/dL. When used as a predictor alongside diabetes mellitus type 2 and ED, CAG repeat length demonstrates a significant linear correlation with serum testosterone levels needed for symptomatic relief. Therefore, providers should consider usage of CAG repeat length alongside patient reported symptoms when creating a treatment plan for hypogonadism.
