Male Hypogonadism

Male hypogonadism refers to a decrease in one or both major functions of the testes — sperm production and testosterone production. The condition reflects the disruption of the hypothalamic-pituitary-gonadal axis: Pulsatile release of gonadotropin-releasing hormone (GnRH) every 60-90 minutes stimulates pulsatile release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from the pituitary into the blood stream. These hormones then stimulate production of testosterone (LH on Leydig cells) and spermatogenesis (FSH on Sertoli cells). Normally, the testes produce approximately 3-10 mg of testosterone daily. In male hypogonadism, the body does not produce enough testosterone or sperm. In this review, we discuss:

• Classification

• Presentation

• Diagnosis

• Treatment

Classification

Classification of hypogonadism is important when determining appropriate treatment and assessing fertility status. Hypogonadism can be classified as:

• primary hypogonadism or hypergonadotropic hypogonadism (testes are primarily affected)

• secondary hypogonadism or hypogonadotropic hypogonadism (pituitary axis is affected)

Presentation

Clinical signs and symptoms of hypogonadism are nonspecific and include:

• decreased libido

• decreased spontaneous erections

• fatigue

• hot flashes

• depressed mood

• difficulty with concentration

• decreased muscle mass

Diagnosis

• Diagnosis is based on clinical signs and symptoms of hypogonadism (see a diagnostic evaluation algorithm (Figure 1) here).

• Low serum testosterone should be checked in the morning and repeated on two occasions to confirm low levels:

  • Testosterone secretion peaks in the morning but the diurnal variation is blunted in men aged 60 years and older.

  • Total serum includes testosterone bound to albumin, sex hormone-binding globulin, and free testosterone (0.5%-2%).

  • Bioavailable testosterone includes testosterone loosely bound to albumin and free testosterone.

• Men should not be routinely screened for hypogonadism without clinical signs and symptoms.

Treatment

• In patients with confirmed hypogonadism, testosterone replacement therapy can be initiated to maintain secondary sexual characteristics, sexual function, and quality of life.

• Before starting treatment, patients should be assessed clinically for prostate cancer risk and obstructive sleep apnea symptoms. Laboratory evaluation should include prostate-specific antigen (PSA) and hematocrit.

• Choosing a testosterone formulation will depend on patient preference.

• Although some study results suggested that testosterone treatment increased cardiovascular risk, in the largest randomized controlled study to date, testosterone replacement did not increase the risk of cardiovascular events in men with hypogonadism.

• Testosterone therapy causes erythrocytosis through several mechanisms: It stimulates bone-marrow production and erythropoietin production, and it suppresses hepcidin, which increases iron availability.

• The prostate is an androgen-dependent tissue, but no association has been reported between testosterone therapy and prostate cancer.

• Testosterone therapy inhibits spermatogenesis. This should be considered in men with low testosterone who are interested in starting a family in the near future.