From the Guidelines
Kallmann syndrome patients should be treated with human chorionic gonadotropin (hCG) and follicle-stimulating hormone (FSH) for fertility, as exogenous testosterone therapy can inhibit spermatogenesis and impair fertility. This approach is based on the most recent guidelines, which emphasize the importance of preserving fertility in patients with hypogonadotropic hypogonadism, such as those with Kallmann syndrome 1. The treatment typically involves hormone replacement therapy to induce puberty and maintain secondary sexual characteristics, with hCG and FSH therapy used to stimulate spermatogenesis and improve fertility.
Key considerations in the treatment of Kallmann syndrome include:
- The use of hCG injections (500-2500 IU, 2-3 times weekly) as the first-line treatment for restoration of testosterone production and spermatogenesis 1
- The addition of FSH injections after testosterone levels are normalized on hCG, to optimize sperm production 1
- The avoidance of exogenous testosterone therapy in males pursuing or planning to pursue family building in the near future, due to its inhibitory effects on spermatogenesis 1
- Regular monitoring of hormone levels, bone density, and development of secondary sexual characteristics to prevent complications like osteoporosis and psychological issues related to delayed puberty 1
In patients with non-obstructive azoospermia, such as those with Kallmann syndrome, clinicians may inform the patient of the limited data supporting pharmacologic manipulation with selective estrogen receptor modulators, aromatase inhibitors, and gonadotropins prior to surgical intervention 1. However, the use of hCG and FSH therapy remains the most effective approach for improving fertility in these patients.
From the Research
Definition and Characteristics of Kallmann Syndrome
- Kallmann syndrome (KS) is a genetic disorder characterized by hypogonadotropic hypogonadism and anosmia 2, 3.
- The syndrome is marked by delayed or absence of puberty and a reduced or absent sense of smell 3.
- KS is a form of hypogonadotropic hypogonadism due to lack of production of sex hormones, which is associated with development of secondary sexual characteristics 3.
Genetic Basis of Kallmann Syndrome
- Six genes are regarded as causal genes of KS, including KAL1, FGFR1, FGF8, CHD7, PROKR2, and PROK2 2.
- Germline mutations in the KAL1 gene can cause deficiency in GnRH hormone, leading to low levels of circulating gonadotropin and testosterone, and ultimately failure of puberty 3.
- KS can be inherited in several manners, including X-linked recessive, autosomal dominant, and autosomal recessive forms 3.
Clinical Manifestations and Diagnosis
- Cardinal features of patients with KS include hypogonadotropic hypogonadism and anosmia or hyposmia 2.
- Non-reproductive, non-olfactory symptoms can also be present, depending on the genetic form of the disease, such as midline cranial anomalies, dental agenesis, and optic problems 2.
- Diagnosis based on clinical findings is important, as the sensitivity of molecular testing of KS is only about 30% 2.
Treatment and Management
- The goal of treatment in women with KS depends on the goal of therapy, which can include inducing and maintaining secondary sex characteristics, and enabling fertility 2.
- Treatment options include estrogen-progestin therapy, gonadotropin, and gonadotropin-releasing hormone therapy 2, 3.
- Early diagnosis, diet supplementation, and medical therapy can help prevent complications associated with KS 3.
- Genetic molecular diagnostics, such as prenatal diagnosis and preimplantation genetic testing, can help reduce the risk of KS in the next generation 3.