Low Testosterone: The Health Implication of Testosterone Deficiency and What Can We Do

Testosterone is an essential sex hormone in men. It is regulated by the brain and produced in the testes. Men start producing testosterone during their pubertal period, and the level tends to decline in their 30s and 40s. Testosterone is vital in the development and maintenance of a male's characteristics. 

Testosterone deficiency affects 7% of males 50 years old and above, with cases increasing as they age. It occurs when the body is no longer able to produce a sufficient amount of testosterone hormone. Low testosterone can have a deleterious impact on a man's sexual well-being and general health, leading to a poor quality of life.

How common is testosterone deficiency?

The incidence of low testosterone increases with age. Based on health screening studies conducted between 2007 and 2009, it is estimated that about 26% of men after the age of 45 in Singapore suffer from testosterone deficiency. The average lifespan of men in Singapore as of 2021 is 83 years old. This means that about 1 in 4 men may experience some degree of health co-morbidities from low testosterone throughout half of their remaining time on earth.

What are the health implications of low testosterone?

Testosterone is a vital hormone that regulates a person's metabolism. It utilises and produces lipids (fats), protein, and carbohydrates. 

Most of us are aware that low testosterone can be associated with low sex drive and erectile dysfunction. We may not know that testosterone deficiency may affect other facets of a person’s physical well-being. A persistent low testosterone state can predispose the body to a constant ‘inflammatory’ state, leading to an increased risk of cardiovascular diseases. 

Health issues such as high cholesterol, heart disease, stroke, insulin resistance, diabetes, hypertension, and obesity are more common in people with testosterone deficiency. There is also medical literature that reveals an increased incidence of sudden death in patients with low testosterone.

The various associated health implications with low testosterone suggest the intricate, essential, and complex role of this male sex hormone in all organs of our body. 

What are the signs and symptoms of low testosterone?

Symptoms that can be associated with testosterone deficiency include:

• Lethargy
• Erectile dysfunction
• Low libido or sex drive
• Infertile
• Reduced energy level
• Poor attention span
• Low mood, depression
• Increased body fat
• Reduced muscle mass
• Reduced bone strength and density
• Reduced body hair or beard production
• Developing breast tissue
• Hot flushes

If you have any of the above symptoms, you might be experiencing testosterone deficiency. You are encouraged to discuss your concerns with your doctor.

How is testosterone produced?

To understand the causes of low testosterone, we must know how this hormone is produced.

The brain, specifically the hypothalamus and pituitary gland, regulates the testes, which control the amount of testosterone released in the bloodstream. The hypothalamus produces a hormone known as gonadotropin-releasing hormone (GnRH) to encourage the pituitary gland to produce luteinising hormone (LH), which in turn regulates the testicles to produce testosterone. 

Low testosterone can be secondary to any disruption of the hypothalamus-pituitary gland-testicles axis. 

What causes low testosterone?

Testosterone generally declines as we age, and this is a physiological progression in health. However, there are other causes associated with low testosterone.

Causes of low testosterone include: 

• Genetic and inborn:
  • Klinefelter syndrome (genetic condition where a male person is born with an extra chromosome gene of XXY rather than XY)
  • Inborn undescended testicles
  • Absence of testicles at birth
• Medical conditions affecting the brain structure and function:
  • Brain tumour/pituitary tumour/prolactinoma
• Medical conditions affecting the structure and function of testicles:
  • Trauma to testicles
  • STD infections, including chlamydia, gonorrhoea, HIV etc
• Underlying systemic illness:
  • Chronic kidney disease
  • Chronic liver disease such as cirrhosis
  • Uncontrolled diabetes mellitus
  • Obesity
  • Obstructive Sleep Apnoea
  • Major surgery
  • Recent cancer treatment, such as chemotherapy or radiotherapy
  • Emotional stress
• Medications:
  • Pain killers
  • Hormone medication

Your healthcare provider can guide you through the possible causes of low testosterone and recommend targeted tests based on your symptoms and past medical history.

How can I test for low testosterone?

Testosterone levels can be evaluated through a blood test. This is commonly done together with other sexual hormone levels, such as brain and testicular hormones, as well for underlying endocrine abnormalities. Depending on individual symptoms and concerns, your doctor may also advise further testing to evaluate the function and structure of the respective organs.

What is the treatment of low testosterone?

Low testosterone levels are usually replaced with hormonal medication in various forms. Currently, in the market, testosterone medications are available in the form of oral, injections, and a gel etc.

Speak to your doctor about which form of testosterone replacement option is more suitable for you and your lifestyle.

What are the potential side effects of testosterone replacement?

Common side effects of testosterone replacement include:

• Acne breakout, oily skin
• Skin irritation over the site of topical medication
• Mild ankle swelling
• Enlarged prostate with abnormal urinary symptoms such as increased nighttime urination, poor flow, hesitancy
• Enlarged breasts, breast tenderness
• Potential infertility (as testosterone replacement can reduce sperm count)

Testosterone replacement may not be suitable for all patients, in particular in those with a history of cancers such as prostate and breast cancers, a history of blood clotting disease, heart failure, or severe untreated obstructive sleep apnoea.

Testosterone replacement is generally safe under the strict titration and follow-up guidance of your doctor, though you should always consult your doctor before starting testosterone replacement. The risks and benefits of the treatment should be discussed prior to beginning the hormonal replacement. Regular follow-up and blood tests are encouraged during testosterone replacement.

Low testosterone with long-term testosterone replacement therapy…

• A controlled and stable testosterone level is achievable with consistent testosterone replacement.
• Replacing the testosterone level is useful in alleviating the negative symptoms of testosterone deficiency.
• A better quality of life with better sex, improved energy level, and better overall bone and muscle mass health may be seen following replacing testosterone level.

References

1. Al-Sharefi A, Wilkes S, Jayasena CN, Quinton R. How to manage low testosterone level in men: a guide for primary care. Br J Gen Pract. 2020 Jun 25;70(696):364-365.
2. Harris E. Meta-Analysis: Low Testosterone in Men Tied to Increased Risk of Death. JAMA. Published online June 07, 2024. doi:10.1001/jama.2024.10334.
3. Harris E. Testosterone Therapy Did Not Increase Major Cardiovascular Events. JAMA. 2023;330(3):211. doi:10.1001/jama.2023.11959
4. Goodale T, Sadhu A, Petak S, Robbins R. Testosterone and the Heart. Methodist Debakey Cardiovasc J. 2017 Apr-Jun;13(2):68-72.
5. Kaur H, Werstuck GH. The Effect of Testosterone on Cardiovascular Disease and Cardiovascular Risk Factors in Men: A Review of Clinical and Preclinical Data. CJC Open. 2021 May 17;3(10):1238-1248.