Research Article: Predictors of early response to GnRH and gonadotropin therapy in pediatric patients with suspected dual congenital hypogonadotropic hypogonadism: a retrospective single-center study
Abstract:
Some patients with congenital hypogonadotropic hypogonadism (CHH) and suspected partial testicular impairment may show variable clinical responses to GnRH and gonadotropin therapy, but predictors of early treatment responsiveness remain unclear. This study aimed to investigate the predictive indicators of early clinical response to GnRH and gonadotropin therapy in pediatric patients with suspected dual CHH.
This retrospective, single-center study included a total of 37 male suspected dual CHH patients who received GnRH or gonadotropin therapy between January 1, 2010, and January 1, 2025. Based on their early treatment response, patients were divided into two groups: favorable early response (n=20) and suboptimal early response (n=17). Patients who failed to achieve a serum testosterone concentration of ?200 ng/dL after ?6 months therapy, had no increase in testicular volume or had no nocturnal emissions during longer follow-up were classified as exhibiting a suboptimal early response. Otherwise, they were classified as exhibiting a favorable early response.
Logistic regression analysis indicated that the level of baseline AMH was positively correlated with a favorable early response (odds ratio = 1.977; 95% confidence interval: 1.010–3.870; p = 0.047). The area under the curve of AMH and testosterone after the hCG prolongation stimulation test was higher, with better sensitivity, specificity, and positive likelihood ratio. When the cut-off value of AMH was 8.9 ng/ml, the sensitivity and specificity were 88.89% and 93.75%, respectively. When the cut-off value of testosterone after the hCG prolongation stimulation test was 51.95 ng/dl, the sensitivity and specificity were 87.5% and 88.89%, respectively.
In this exploratory pediatric cohort with suspected dual CHH, baseline AMH and testosterone after the hCG prolongation test were associated with early response to GnRH and gonadotropin therapy. These findings may help stratify treatment responsiveness, but require validation in larger cohorts with standardized treatment protocols and objective semen-based endpoints.
Introduction:
Congenital hypogonadotropic hypogonadism (CHH) is a disorder caused by impaired synthesis, secretion, or function of gonadotropin-releasing hormone (GnRH) ( 1 ), resulting in compromised gonadal activity and hypogonadism. Patients with CHH manifest with micropenis and/or cryptorchidism, absent or delayed puberty, or infertility ( 2 ). According to the findings of Sykiotis et al., based on different responses to long-term GnRH replacement therapy, CHH can be divided into three types: triple defect, dual defect…
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