Male hypogonadism is the result of a deficiency in the male sex hormone: testosterone. This leads to loss of libido and sexual function, delayed puberty, osteoporosis and may also result in an inability to produce sperm.
What is Male Hypogonadism?
Male hypogonadism describes a state of low testosterone levels in men. Testosterone is produced in the testicles and is important in the development of male characteristics such as deepening of the voice, development of facial and pubic hair, and growth of the penis and testicles during puberty. Pituitary gonadotropin-releasing hormone, produced in the hypothalamus, stimulates the pituitary gland to produce luteinizing hormone and follicle-stimulating hormone (gonadotropins), which then act on the testicles, allowing them to produce testosterone. Low testosterone levels can occur due to pathologies affecting the testicles or conditions affecting the hypothalamus or pituitary gland. Men can be affected at any age and experience different symptoms depending on when the disease occurs relative to the onset of puberty.
What Causes Male Hypogonadism?
Male hypogonadism can be divided into two groups. Classical hypogonadism; low testosterone levels are caused by a specific underlying medical condition, for example Klinefelter syndrome, Kallmann syndrome or a pituitary tumor. Late hypogonadism; declining testosterone levels are linked to general aging and/or age-related diseases, particularly obesity. Late-onset hypogonadism is thought to affect only a minority of men over the age of 40.
There are two types of classic male hypogonadism: primary and secondary. Hypogonadism is said to be primary when the low level of testosterone is due to conditions affecting the testicles. Primary hypogonadism is also called hypergonadotrophic hypogonadism, characterized by excessive production of luteinizing hormone and follicle-stimulating hormone (gonadotropins) by the pituitary gland, in an attempt to stimulate the testicles to produce more testosterone. However, as the testicles are affected or missing, they are unable to respond to the increased levels of gonadotropins and little or no testosterone is produced.
Examples of conditions affecting the testes that lead to low testosterone levels:
– inflammation due to infections such as mumps – chemotherapy or radiotherapy to the testicles – failure of the testicles to descend into the scrotum – absence of the testicles (anorchidism) – Klinefelter syndrome – a genetic condition in which men are born with an extra X chromosome; characterized by large size, reduced fertility and development of breast tissue – certain types of tumors – certain types of autoimmune disorders.
Secondary hypogonadism results from conditions affecting the function of the hypothalamus and/or pituitary gland. It is also known as hypogonadotrophic hypogonadism due to low levels of luteinizing hormone and follicle-stimulating hormone, resulting in decreased testosterone production. Secondary hypogonadism often occurs as part of a larger syndrome of hypopituitarism. Causes may include:
– pituitary tumors and their treatment – isolated hypogonadotrophic hypogonadism (low GnRh levels since birth) – Kallmann's syndrome – a rare genetic disease, which causes loss of development of nerve cells in the hypothalamus that produce GnRH. This results in an absence of puberty, sexual maturation and non-development of the testicles – use of anabolic steroids – obesity – Prader-Willi Syndrome – head trauma
What are the signs and symptoms of male hypogonadism?
Signs and symptoms depend on the phase at which hypogonadism occurs in relation to sexual maturity. If testosterone deficiency occurs before or during puberty, signs and symptoms are likely to include:
Delayed puberty:
– lack of development of the testicles and lack of growth of the penis – lack of pubic and facial hair – no worsening of the voice – absence of sperm production in the testicles, leading to infertility. – delayed bone age (when the maturity of the skeleton is several years behind the age).
At the time of puberty, boys with insufficient testosterone may also have subnormal strength and endurance, and their arms and legs may continue to grow disproportionately to the rest of the body.
In men who have already reached sexual maturity, symptoms are likely to include:
– insufficient erections, loss of libido and poor sexual performance – fatigue – loss of motivation and concentration – loss of pubic and facial hair- decreased sperm count – small and flabby testicles – mood changes – increased body fat – gynecomastia – growth of breast tissue – thinning of bones (osteoporosis) – reduced muscle mass and physical strength – skin wrinkled like a "parchment"
As some of these symptoms (eg, fatigue, mood swings) can have multiple causes, male hypogonadism can sometimes go unnoticed at first visit.
How common is male hypogonadism?
Male hypogonadism is more common in aging men. Testosterone levels in men begin to decline after age 40. It is estimated that 8.4% of men between the ages of 50 and 79 suffer from testosterone deficiency. Male hypogonadism is also linked to type 2 diabetes: it is estimated that around 17% of men with type 2 diabetes have low testosterone levels.
Is male hypogonadism hereditary?
Male hypogonadism is not hereditary. There are genetic causes of hypogonadism, which include Klinefelter syndrome and Kallmann syndrome; however, these diseases occur sporadically, they are not inherited from parents.
How is male hypogonadism diagnosed?
A detailed medical history should be taken. Of particular importance is whether virilization was complete at birth, whether the testicles descended, and whether the patient reached puberty at the same time as his peers. The patient should be carefully examined, the presence and size of the testicles recorded, and whether they are properly seated in the scrotum.
Many of the symptoms of male hypogonadism are nonspecific and can be caused by different pathologies. Therefore, when diagnosing hypogonadism, it is important that biochemical tests are performed to assess blood testosterone levels and confirm the diagnosis. Blood tests are done to measure testosterone levels. The blood sample should preferably be taken at 9 am (because testosterone levels fluctuate throughout the day), the sample can be taken on an outpatient basis. If the result of the first test shows low testosterone, the test should be repeated after two or three weeks to confirm the result. Other hormones are also tested after the second blood draw, such as luteinizing hormone, follicle-stimulating hormone and prolactin (produced by the pituitary gland). The results of these blood tests will help distinguish between primary (low testosterone and high gonadotropins) and secondary (low testosterone and normal or low gonadotropins) hypogonadism.
Depending on the results of the above tests, further investigations may be conducted, such as: bone densitometry test to assess the impact of testosterone deficiency on bones; semen analysis; genetic studies; and ultrasound of the testicles to detect the presence of any nodules or growths.
What are the treatments for male hypogonadism?
Treatment for classic hypogonadism involves testosterone substitution with the goal of restoring normal testosterone levels in the blood. Treatment will vary between patients and will be tailored to their individual needs. Different testosterone preparations are available:
1- Injectable form – these are preparations that can be administered every three to four weeks or every three months, intramuscularly.
2- Daily application (in the morning) of testosterone gel on the skin.
3- Oral Testosterone – tablet placed on the upper gum in the mouth.
4- Testosterone implants – small pellets placed under the skin.
All of these treatments are outpatient and should be discussed with a healthcare professional so that the most appropriate treatment is chosen. During testosterone replacement therapy, regular blood tests should be done to monitor testosterone levels and adjust the dose if necessary to maintain normal levels. Oral testosterone tablets are not recommended due to possible liver damage.
Testosterone should not be administered if the patient has prostate cancer. Before starting testosterone treatment, a blood test to measure a hormone produced by the prostate called PSA (prostate specific antigen) is done (PSA levels are elevated in prostate cancer). The prostate may also be examined (via digital rectal examination) to rule out prostate cancer.
For patients who have been diagnosed with late hypogonadism, there are currently not enough studies to know if treatment with testosterone is safe and effective in the long term. Although there are short-term studies that indicate it may benefit these patients over a short period of time, long-term clinical trials are needed. These should involve the follow-up of a large number of patients, to assess the long-term impact of testosterone treatment in patients with late-onset hypogonadism. Areas that require particular attention are assessing the effects of treatment on the likelihood of developing cardiovascular disease, prostate cancer and secondary polycythaemia (a condition where too many red blood cells are present in the blood).
Are there any side effects to this treatment?
There may be mild side effects depending on the form used: injectable forms may cause pain and bruising at the injection site; the gel can cause skin irritation; and the tablets can cause gum irritation.
Treatment with testosterone can cause an increase in red blood cells (known as polycythemia), which increases the risk of thrombosis. Regular blood tests should be carried out during treatment to detect any increase in the number of red blood cells. Another serious side effect that should be watched for is prostate enlargement. Prostate examination and a PSA blood test should be done every three months for the first year, then once a year in men over 40 from the start of treatment. If patients are concerned about these possible side effects, they should discuss them with their treating physician.
What are the long-term implications of male hypogonadism?
Symptoms of male hypogonadism, such as lack of libido, insufficient erections, and infertility, can cause low self-esteem and lead to depression. Psychological support is advised to help cope with these side effects; patients should speak to their doctor for more information. Patients generally notice an improvement in their libido and self-esteem after replacement therapy.
Male hypogonadism has been shown to increase the risk of developing heart disease (low testosterone levels can lead to increased cholesterol levels). Studies have shown that testosterone levels may be lower in men with type 2 diabetes and in overweight men. Thus, exercising more and losing weight can increase testosterone levels in men with diabetes.
Testosterone levels in men naturally decline as they age. In the media, we sometimes talk about male menopause (andropause). Low testosterone levels can also cause difficulty concentrating, memory loss, and trouble sleeping. Current research suggests that these effects are only seen in a minority of older men. However, there is a lot of ongoing research aimed at learning more about the effects of testosterone in older men and the possible benefits of testosterone replacement therapy.