Congenital combined pituitary hormone deficiency patients have better responses to gonadotrophin-induced spermatogenesis than idiopathic hypogonadotropic hypogonadism patients

STUDYQUESTION: Dopatients with congenital combined pituitary hormone deficiency(CCPHD) have different responses to gonadotrophin- induced spermatogenesis compared with those with idiopathic hypogonadotropic hypogonadism (IHH)? SUMMARY ANSWER: CCPHD patients have a better response to gonadotrophin therapy than IHH patients. WHAT IS KNOWN ALREADY: Gonadotrophins are effective in inducing spermatogenesis in patients with hypogonadotropic hypogonadism. DESIGN, SIZE AND DURATION: This retrospective cohort study included 75 patients, 53 of whom had IHH and 22 CCPHD. They were diagnosed, treated and followed up between January 2008 and December 2013. PARTICIPANTS/MATERIALS, SETTING AND METHODS: Combined gonadotrophin therapy, consisting of human chorionic gonadotrophin and human menopausal gonadotrophin, was administered for 24 months. The success rate of spermatogenesis (>= 1 sperm in ejaculate), serum total testosterone level, testicle size and spermconcentration during the treatment, as well as the first time sperm were detected in the ejaculate, were compared between the two diagnostic groups. All patients were treated in Peking Union Medical College Hospital. MAIN RESULTS AND THE ROLE OF CHANCE: Spermatogenesis was successfully induced in 85% of IHH patients and 100% of CCPHD patients after 24-month combined gonadotrophin treatment (P = 0.03). In comparison with IHH, CCPHD patients had larger mean testicle sizes during the gonadotrophin treatment at 6, 12, 18 and 24 months (all P< 0.05). The initial time for sperm appearance in IHH group (n = 45) and CCPHD group (n = 22) was 13.2 +/- 5.9 versus 10.4 +/- 3.8 months (P = 0.045). Generally, CCPHD patients had higher sperm counts [median (quartiles)] than IHH patients during the treatment, but the difference was only statistically significant at 12 months of treatment, 3.3 (1.8, 12.0) versus 1.0 (0.0, 4.6) million/ml, P = 0.001. There was a higher level of serum total testosterone [mean (SD)] in the CCPHD group than the IHH group (676 +/- 245 versus 555 +/- 209 ng/dl, P = 0.035). LIMITATIONS, REASONS FOR CAUTION: First, the inherent nature of a retrospective designed studywas a main shortcoming. Secondly, pathological genemutations in IHH and CCPHDpatients should be further investigated. Clarification of the underlyingmechanisms between cryptorchidismandmutatedgenesmayprovidemore informationfor thedivergent therapeutic responsesbetween twogroups. Only aminorityofpatients were actively seeking to have children so information about fertility is limited. WIDER IMPLICATIONS OF THE FINDINGS: CCPHDpatients had a lower incidence of cryptorchidismand a better response to gonadotrophin therapy than IHHpatients, reflectingmultiple defects on the different levels of reproduction axis in IHH. Furthermore, growth hormone is not indispensable for spermatogenesis in CCPHD patients.