Endocrine Abstracts

CHH is a rare disease with a relevant genetic background, and is characterized by a failure to enter (complete forms) or to complete (partial forms) pubertal development. It requires a treatment to allow the completion of puberty, and in male this goal can be achieved either using testosterone replacement therapy or administering gonadotropins (Gn); the latter allows both testicular development and the endogenous testosterone production. There are few studies evaluating the therapy with Gn in CHH pubertal induction and there is no consensus on the protocol to be used. In this retrospective analysis we aimed to (i) investigate clinical and biochemical predictors of testicular response to Gn-induced puberty in CHH; (ii) study the non-reproductive outcomes of this treatment (height, body proportions) and their determinants. We retrospectively studied 19 CHH male patients, undergoing two years of Gn-mediated puberty induction with FSH and hCG, started between the ages of 14 and 23 years. For each patient clinical history, physical examination, hormonal evaluation, and genetic analysis using Targeted Next Generation Sequencing for CHH genes were performed; 8 patients performed a semen analysis (SA) at the end of their treatment. The Mann-Whitney test and multiple regression analysis showed a lesser increase in testicular volume after 24 months of induction, to be significantly associated with: (i) cryptorchidism; (ii) a positive genetic background; (iii) a complete form of CHH. We found no significant correlation with the cumulative dose of hCG administered in 24 months. We found no association with the results of SA, probably due to the low numerosity. The multiple regression analyses investigating the eunuchoid habitus and a measure of the difference of subject’s final height from his target (deltaSDSth), found a significant relation with: (i) the age at the beginning of the induction; (ii) the duration of growth during the induction; (iii) for deltaSDSth, also the bone age before the induction. The duration of growth during induction resulted to be associated with previous testosterone priming and with partial forms of CHH. In conclusion, this study shows that genetic forms of CHH, as well as cryptorchidism, are negative predictors of testicular response. This could be because they determine a complete GnRH deficiency since intrauterine life. We also found that the eunuchoid habitus and deltaSDSth are associated not only with a delay in the treatment, but also with the duration of growth during the induction, which is apparently related to previous androgenization.