Predictors of pilosebaceous unit responsiveness to testosterone therapy in patients with hypogonadotrophic hypogonadism

Testosterone replacement therapy is the mainstay of treatment in male patients with isolated hypogonadotrophic hypogonadism (HH) to achieve virilisation. However, responsiveness of pilosebaceous unit (PSU) to testosterone replacement therapy in these patients is quite variable. Androgen action is inversely proportional to the number of CAG repeats in exon 1 of androgen receptor gene; therefore, we hypothesised that CAG repeat length contributes to testosterone responsiveness in patients with HH. The CAG repeat length in 21 well-virilised men (hair score > 30, responders) and 25 poorly virilised men (hair score ≤ 30, non-responders) with HH on optimal testosterone replacement therapy at least for a period of 1 year was analysed. Serum LH, FSH, testosterone and 17 β oestradiol were estimated. Polymerase chain reaction (PCR) amplification of exon 1 of androgen receptor gene was performed from genomic DNA, and these PCR-amplified products were sequenced for the number of CAG repeats. The difference between number of CAG repeats in responders and non-responders was statistically significant (19.19 ± 3.25 and 22.24 ± 2.65, P = 0.001) and showed a strong negative correlation with total body hair score (r = -0.538 and P = 0.0001). In conclusion, these results suggest that the number of CAG repeats influences the responsiveness of PSU to testosterone treatment in patients with HH.