Pharmacogenetic aspects of testosterone therapy

Considering observations in eugonadal men, one can assume that testosterone therapy in hypogonadal men should have a differential impact on androgen target tissue, depending on the number of CAG repeats. In a longitudinal pharmaco-gentic study in 131 hypogonadal men, prostate volume was assessed before and during androgen substitution. Considered were the length of CAG repeats, sex hormone levels and anthropometric measures. Initial prostate size of hypogonadal men was dependent on age and baseline testosterone levels, but not the CAG repeat polymorphism. However, when prostate size increased significantly during therapy, prostate growth per year and absolute prostate size under substituted testosterone levels were strongly dependent on the AR polymorphism, with lower treatment effects in longer repeats. Other modulators of prostate growth were age and testosterone levels during treatment. The odds ratio for men with repeats < 20 compared to those with > 20 to develop a prostate size of at least 30 ml under testosterone substitution was 8.7 (95% CI 3.1 - 24.3, p < 0.001). This first pharmacoge-netic study on androgen substitution in hypogonadal men demonstrates a marked influence of the CAG repeat polymorphism on prostate growth (Zitzmann et al. 2003b).

Another retrospective approach concerning pharmacogenetic influences in hormonal male contraception demonstrated sperm counts to be more easily suppressed by various pharmacological regimens in men with longer CAG repeats as spermato-genesis is partially dependent on intratesticular androgen activity. This was only observed in the subgroup with residual gonadotropin activity, causing stimulatory effects on spermatogenesis and Leydig cell production of testosterone which can bind to intratesticular androgen receptors, hence making differences caused by the CAG polymorphism visible (von Eckardstein etal. 2002). When the distinction in regard to gonadotropin secretion is not made, the difference between individuals with long or short CAG repeats cannot be observed, as testicular androgen receptors will not be activated in persons lacking LH and, hence, intratesticular testosterone (Yu and Handelsman 2001).

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Hair Loss Prevention

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