European Consensus Statement on congenital hypogonadotropic hypogonadism—pathogenesis, diagnosis and treatment

Congenital hypogonadotropic hypogonadism (CHH)—a rare disorder caused by deficient production, secretion or action of gonadotropin-releasing hormone—results in an absence of puberty and infertility. Here, Ulrich Boehm and colleagues summarize approaches for the diagnosis and treatment of CHH in light of recent discoveries. This Consensus Statement differs from existing guidelines for the treatment of hypogonadism as it focuses exclusively on CHH. Congenital hypogonadotropic hypogonadism (CHH) is a rare disorder caused by the deficient production, secretion or action of gonadotropin-releasing hormone (GnRH), which is the master hormone regulating the reproductive axis. CHH is clinically and genetically heterogeneous, with >25 different causal genes identified to date. Clinically, the disorder is characterized by an absence of puberty and infertility. The association of CHH with a defective sense of smell (anosmia or hyposmia), which is found in ∼50% of patients with CHH is termed Kallmann syndrome and results from incomplete embryonic migration of GnRH-synthesizing neurons. CHH can be challenging to diagnose, particularly when attempting to differentiate it from constitutional delay of puberty. A timely diagnosis and treatment to induce puberty can be beneficial for sexual, bone and metabolic health, and might help minimize some of the psychological effects of CHH. In most cases, fertility can be induced using specialized treatment regimens and several predictors of outcome have been identified. Patients typically require lifelong treatment, yet ∼10–20% of patients exhibit a spontaneous recovery of reproductive function. This Consensus Statement summarizes approaches for the diagnosis and treatment of CHH and discusses important unanswered questions in the field.