Testosterone production declines naturally with age. Testosterone deficiency (TD) may result from disease or damage to the hypothalamus, pituitary gland, or testicles that inhibits hormone secretion and testosterone production, also known as hypogonadism. Depending on age, insufficient testosterone production can lead to abnormalities in muscle and bone development, underdeveloped genitalia, and diminished virility.

Testosterone is the androgenic hormone primarily responsible for normal growth and development of male sex and reproductive organs, including the penis, testicles, scrotum, prostate, and seminal vesicles. It facilitates the development of secondary male sex characteristics such as musculature, bone mass, fat distribution, hair patterns, laryngeal enlargement, and vocal chord thickening. Additionally, normal testosterone levels maintain energy level, healthy mood, fertility, and sexual desire.

The testes produce testosterone regulated by a complex chain of signals that begins in the brain. This chain is called the hypothalamic-pituitary-gonadal axis. The hypothalamus secretes gonadotropin-releasing hormone (GnRH) to the pituitary gland in carefully timed pulses (bursts), which triggers the secretion of leutenizing hormone (LH) from the pituitary gland. Leutenizing hormone stimulates the Leydig cells of the testes to produce testosterone. Normally, the testes produce 4–7 milligrams (mg) of testosterone daily.

Incidence and Prevalence

Testosterone production increases rapidly at the onset of puberty and decreases rapidly after age 50 (to 20% to 50% of peak level by age 80). Approximately 8 million men in the United States experience testosterone deficiency; approximately 600,000 receive treatment.

Types and Causes

Hypogonadsim is classified by the location of its cause along the hypothalamic-pituitary-gonadal axis:

• Primary, disruption in the testicles

• Secondary, disruption in the pituitary

• Tertiary, disruption in the hypothalamus

Signs and Symptoms

Signs depend on the age of onset and the duration of hormonal deficiency. Congenital hypogonadism is generally characterized by underdeveloped genitalia (testes that do not descend into the scrotum) and, occasionally, undeterminable genitalia. The development of hypogonadism near puberty can result in gynecomastia (enlargement of breast tissue), sparse or absent pubic and body hair, and underdeveloped penis, testes, and muscle. Adult men may experience diminished libido, erectile dysfunction, muscle weakness, loss of body hair, depression, and other mood disorders.

Complications

Testosterone deficiency has been linked to muscle weakness and osteoporosis. In one study, proximal and distal muscle weakness was detected in 68% of men with primary or secondary hypogonadism. Spinal, trabecular, and radial cortical bone density may also be significantly reduced in testosterone-deficient men. Thirty percent of men with spinal osteoporosis have long-standing testosterone deficiency, and one-third of men have subnormal bone density that puts them at risk for fracture.