Testosterone is a male sex hormone that plays a key role in reproductive and sexual function. It is predominantly produced in the testes and in small amounts by the adrenal glands. Testosterone is responsible for the development of the male secondary sexual characteristics (such as facial and body hair) during puberty. It also stimulates the testes to produce sperm. Testosterone is also important for overall good health. It has an important role in the growth of bones and muscles, and stimulates the bone marrow to make red blood cells. Testosterone affects one’s sex drive (libido), mood and some aspects of mental ability.
How is low testosterone categorised?
When the body does not produce enough testosterone for it to function normally, one is said to have low testosterone levels or testosterone deficiency or hypogonadism. This lack of production is categorised as:
- Primary (due to diseases of the testes) or
- Secondary (due to diseases of parts of the brain – hypothalamus and pituitary gland).
Primary hypogonadism is more common in younger men and is often due to genetic abnormalities. Late onset or secondary hypogonadism is more common in older men.
How common is it?
Low testosterone becomes more common with age. The prevalence varies in specific studies due to the different population studied and the definition used. The Bach studies and the Mass Male Aging studies at the New England Research Institute quote the prevalence of hypogonadism at about 6%.
What are the symptoms of low testosterone?
The symptoms are different depending on the age of the patient.
In a teenager with primary hypogonadism, symptoms are:
- Failure to go through with normal puberty.
- Poor development of facial, body or pubic hair.
- Breast development.
- The voice does not deepen.
- Poor muscle development.
- Poor growth in height.
In an adult, the symptoms are:
- Sexual symptoms are characterised by diminished libido or impaired sexual performance like erectile dysfunction.
- Mood changes (irritability).
- Low energy.
- Reduced muscle strength.
- Breast development.
- Low semen volume.
- Reduced bodily hair growth.
- Thinning of the bones.
Is there such a thing as a male menopause?
The term ‘male menopause’ is not accurate. Menopause is the cessation of menstruation (periods) in women. In men, the testosterone levels do not drop off suddenly and instead, do so slowly with age.
What medical conditions are associated with low testosterone?
Obesity, type 2 diabetes and metabolic syndrome (hypertension, high cholesterol) have been shown to be associated with low testosterone levels. Some epidemiologic studies suggest a link between low testosterone and cardiovascular disease and death, but this has never really been confirmed with a randomised controlled trial.
Does testosterone replacement therapy (TRT) increase one’s cardiovascular risks?
This association has been suggested by a recent small study that was published in the New England Journal of Medicine (Testosterone and Mobility study). However, this study’s primary endpoint was looking at how TRT improves a patient’s mobility, and not the cardiovascular risks. Moreover, the study subjects were of an older, frail group with multiple medical problems and the sample size was small. There are other small studies in the UK looking at patients with heart failure and angina, and they found that TRT actually improved these heart conditions. Therefore, the association of TRT and cardiovascular risks is not conclusive, and one should still monitor for these complications.
How is it diagnosed?
The diagnosis is based on two things – symptoms or signs of low testosterone levels and also a blood test. Blood measurements of testosterone levels should be done in the morning (between 0800 and 1000) because there is a natural peak in the morning. At least two blood samples on different days are taken to measure total testosterone levels. A normal testosterone reference range for healthy young adult men is between 8 and 27 nanomolar but this may differ slightly between different laboratories.
The Androgen deficiency in aging men (ADAM) Questionnaire is useful for assessing men with symptoms of low testosterone.
What other tests may be done?
Other hormone tests (FSH and LH) may be needed to differentiate between primary and secondary hypogonadism. Other measurements of testosterone such as free testosterone levels may also be done. Genetic testing may be done to look for genetic problems. A sperm analysis can be done to check for fertility. A CT or MRI is useful to look for brain abnormalities (pituitary gland problems). Prolactin (another hormone) levels are elevated in the presence of a benign tumour of the pituitary.
What are the main forms of testosterone replacement therapy?
In Australia, testosterone injections, implants, capsules, gels and patches are available. Treatment is generally life-long.
Testosterone injections are given into the muscle usually every 2 to 3 weeks. There may be a wide variation (initial spike then sudden drop off) in the testosterone levels from this route of administration. A longer-acting (up to 14 weeks) injectable form (Reandron) is now approved in Australia. The testosterone is released slowly so that men are less likely to experience the high or low levels of testosterone that are common with standard injections.
Small pellets are placed under the skin of the abdomen or buttock under local anaesthetic. These are long-acting and can last between 4 to 6 months and are not removable. About 10% of the pellets may get pushed out of the skin eventually.
One or two capsules are normally taken 3 times a day, with fatty food or drink to help absorption. This form of treatment does not usually fully replace testosterone levels and is chosen when other forms of treatment are not suitable.
This is a popular form of treatment. The gel is rubbed into the skin once a day and results in a relatively constant concentration of testosterone over 24 hours. Men should avoid physical contact with others for 4 hours after applying the gel to avoid transferring the testosterone.
These patches are usually put on at night and worn at all times. About 10% of men develop a skin rash when using the patch.
What are the risks and side effects of testosterone replacement?
Side effects include:
- Increased risk of prostate cancer.
- Increase in prostatic growth and worsening symptoms related to benign enlargement of the prostate.
- Impaired sperm production.
- Increase red blood cell production (haematocrit) causing problems with blood circulation and increasing cardiovascular risks.
- Uncommonly mild acne, weight gain, breast development, hair loss, aggressive mood swings. sleep apnoea, migraines.
Who should not get testosterone replacement therapy (TRT)?
- Men with prostate cancer or those suspected of having prostate cancer should not have TRT.
- Men who are still planning to have children should defer TRT as it can affect fertility. If sperm production was previously normal, it usually recovers several months after stopping treatment. Men with primary hypogonadism (testicular problem) may already be infertile before TRT starts.
- Men who have normal levels of testosterone. If these men receive TRT, their own testes will stop producing testosterone and this may take a long time to reverse after stopping TRT.
- Men with breast cancer.
How are patients who are having treatment monitored?
- PSA blood tests and prostate examinations should be done regularly to monitor for the development of prostate cancer.
- Blood tests looking at haematocrit (HCT) should be done to assess the risks of cardiovascular and clotting events.
- Measuring testosterone levels to adjust treatment dosing.
- For those men with thin bones, regular bone density checks (DEXA scan) will be needed to see if there is improvement after TRT.