Virtual Medical Centre

Testosterone Deficiency (Primary Hypogonadism and Secondary/Hypogonadotrophic Hypogonadism)

• What is Testosterone Deficiency?
• Who gets Testosterone Deficiency?
• Predisposing Factors
• Progression
• Probable Outcomes
• How Will Testosterone Deficiency Affect Me?
• Clinical Examination
• How is Testosterone Deficiency Diagnosed?
• How is Testosterone Deficiency treated?
• Testosterone Deficiency References
• Drugs/Products Associated with Testosterone Deficiency

What is Testosterone Deficiency?

Male hypogonadism is a disorder in which a man has testosterone deficiency, that is, he produces abnormally low levels of the male sex hormone testosterone. As testosterone plays an important role in regulating the male sex drive, supporting the development of sperm and developing male sex characteristics (e.g. deep voice, facial hair), testosterone deficiency often results in symptoms such as reduced sex drive and infertility. These symptoms can also affect a man's self esteem and his overall sense of well-being.

Testosterone in males is produced in the testicles. Testosterone deficiency arises when the testicles fail to produce enough testosterone. There are two causes of testosterone deficiency:

1. Impaired testicular function: Referred to by health professionals as primary hypogonadism or testicular failure. This condition arises because the man's testicles have some abnormality preventing them from producing testosterone; and
2. Impaired pituitary or hypothalamus function: Referred to by health professionals as hypogonadotrophic or secondary hypogonadism. This condition arises because the function of the pituitary and/or hypothalamus (the two glands in the brain that regulate hormone production) is impaired.

Who gets Testosterone Deficiency?

Estimates of the proportion of men who experience hypogonadism vary considerably, from 0.5% to 50%. The large differences in prevalence estimates are mainly caused by differences between the groups of men studied. For example, some studies have been conducted amongst older men, who are more likely to have hypogonadism than younger men. Therefore these studies would be likely to over-estimate the proportion of men who are testosterone deficient.

Differences also arise because of the different ways in which testosterone deficiency is diagnosed. Some studies use clinical indicators (symptoms such as lack of body hair or low sex drive) to diagnose testosterone deficiency, and these studies consider all men with clinical symptoms to be testosterone deficient. Others diagnose testosterone deficiency based on the levels of testosterone a man has in his blood. However, many men with abnormally low levels of testosterone in their blood do not have clinical symptoms of hypogonadism, while many of those with normal levels of blood testosterone have symptoms that suggest they are testosterone deficient. Studies that measure blood testosterone usually report a lower prevalence of testosterone deficiency than studies that use clinical symptoms as the measure.

The best available evidence about the prevalence of hypogonadism comes from a large study of men of various ages in a community in the United States. That study reported that 5.6% of men aged 30–79 years of age were testosterone deficient. Prevalence of testosterone deficiency increases in men aged over 50, of whom about 20% are testosterone deficient.

For more information on testosterone deficiency in men > 40 years of age, see Andropause.

Predisposing Factors

There are a number of factors that increase the likelihood of a man experiencing hypogonadism. These factors vary depending on whether the testosterone deficiency is caused by primary testicular failure or secondary hypogonadism (pituitary or hypothalamus failure).

Primary testicular failure

Primary testicular failure can result from numerous causes, including:

• Klinefelter's syndrome: Klinefelter's syndrome is a congenital syndrome in which males have an abnormal number of chromosomes in their cells. Normally, there are 46 chromosomes in each cell, including two sex chromosomes (either X or Y). Men with Klinefelter's syndrome have 47 chromosomes per cell, three of which are sex chromosomes (XXY). This chromosomal abnormality is the most common cause of primary testicular failure, and affects around 1 in 600 men;
• Bilateral orchiectomy: Bilateral orchiectomy, the removal of both testicles, for example due to testicular cancer;
• Cancer treatment: Either radiotherapy or chemotherapy can induce testicular failure because the medication used to treat cancer damages the testes. of reproductive age may choose to cryopreserve sperm before undergoing cancer treatment, so that they can use assisted reproduction techniques to have children later in their life;
• Cryptorchidism: Cryptorchidism is condition in which the testicles fail to descend from the abdominal cavity into the scrotum during infancy. Other childhood conditions in which the testicles fail to develop normally can also cause primary testicular failure;
• Testicular trauma: For example, an injury in which the testicles were crushed or constricted;
• Orchitis: Orchitis, or inflammation of the testicles, may be induced by mumps or infectious conditions of the genitourinary system;²
• Age: Testosterone levels decrease by approximately 1% each year once a man reaches his late thirties, and the rate of decline may increase to 2–3% per annum as he ages. Chronic health conditions (which increase in prevalence with age), such as diabetes, and the medications used to treat them further reduce testosterone levels;
• Obesity: Obese men have lower testosterone levels than their non-obese counterparts and are more likely to be testosterone deficient. A study of Australian men aged 54–89 years reported that obese men were almost twice as likely to have low levels of testosterone in their blood compared to their non-obese counterparts;
• Diabetes;
• Metabolic syndrome;
• Environmental exposure: To anti-androgens and xenoestrogens, for example by men who work with chemicals containing these compounds.

Secondary hypogonadism or hypogonadotrophic hypogonadism

Secondary hypogonadism arises from conditions that affect the functioning of either the hypothalamus or pituitary gland. These conditions include:

• Pituitary tumours: In particular prolactinoma (a benign pituitary tumour that produces the hormone prolactin). Such tumours are the most common cause of secondary hypogonadism. Tumours arising in the cranio-pharyngeal pouch are also associated with testosterone deficiency caused by hypothalamic or pituitary failure;
• Iron overload disorders: Including thalassaemia (a genetic condition predisposing an individual to anaemia) and haemochromatosis (a genetic condition in which iron from the blood is deposited into organs, including the heart, liver and pancreas);
• Genetic causes: Other genetic conditions affecting the production of hormones;
• Illness: Illnesses, including acute critical and chronic illness and their treatments, may induce temporary or ongoing secondary hypogonadism;
• Substance abuse: Substance abuse, including excessive consumption of opiates and steroids, is associated with an increased likelihood of testosterone deficiency.

Progression

Some 95% of the testosterone in a man's body is produced in the Leydig cells, which are found in the testes. Hypogonadism arises when the testicles fail to produce sufficient testosterone. Testosterone production occurs in response to hormonal signals from the hypothalamus and pituitary glands in the brain. These glands produce gonadotrophin releasing hormone (GnRH), follicle stimulating hormone (FSH) and luteinising hormone (LH).

GnRH is produced by the hypothalamus. Its role in sperm production is to trigger the production of FSH by the pituitary. FSH triggers the production of sperm by the testicles. The produced sperm requires LH (also produced by the pituitary) to properly develop and mature. These hormones also stimulate the testes to produce testosterone, which, along with LH, supports the development and maturation of sperm. Testosterone is also responsible for the development of secondary sex characteristics in men, including the development of adult-sized genital organs, facial hair growth, bone and muscle growth, and a deep voice.

Because testosterone is responsible for the development of secondary sex characteristics, hypogonadism can lead to the non-expression or under-expression of these characteristics. Testosterone deficiency is therefore associated with a number of visible features, including:

• Small, firm or undescended testes;
• Small penis size;
• Absent or decreased facial, pubic and body hair; and
• Gynaecomastia (breast growth).

Hypogonadism is further characterised by lower than normal levels of testosterone in the blood. Because testosterone is necessary for sperm production, hypogonadism can also lead to infertility caused by non-obstructive azoospermia (absence of sperm in the semen despite no obstructions in the ducts that transport sperm out of the testicles).