Is Low Testosterone Genetic?

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Testosterone is a critical hormone that plays a key role in men’s health, affecting everything from energy levels and muscle mass to mood and libido. However, low testosterone (low T) is a condition that affects approximately 10-40% of men (UW Health 2017), depending on age and health factors. Symptoms like fatigue, reduced strength, and low sex drive can significantly impact quality of life, leaving many men searching for answers about why their testosterone levels are dropping.

But is low testosterone simply a product of lifestyle choices and ageing, or could genetics play a more significant role?

In this article, we examine the link between low testosterone and genetics. We’ll explore the specific genes linked to testosterone production and scientific studies and environmental factors that cause low testosterone. Whether you’re experiencing symptoms or curious about your family health history, this article will shed light on the connection between your DNA and testosterone levels.

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Testosterone deficiency and its symptoms

Testosterone is an androgen produced in both men and women. However, it is secreted in large amounts in adult males and smaller quantities in women.

Serum testosterone (T) levels are important to normal sexual development and the maintenance of a healthy body in adult males. They fluctuate throughout a man’s life. They reach their peak during the late teens and early twenties and then start declining at 30.

Some men have lower levels (below 300 ng/dL). It can be due to a medical condition, lifestyle, old age, or other factors. Whatever the cause, men with low T experience similar mental, physical, and emotional symptoms.

Men with low T often report the following symptoms.

• Decline in muscle mass
• Reduced bone density
• Reduced sex drive
• Reduced sperm count
• Erectile dysfunction
• Shrinking testicles
• Increase in the breast size
• Fatigue
• Lack of concentration
• Depression

The SHBG Gene and Low Testosterone

Testosterone levels in the body typically peak when men are in their late teens and early twenties, After which levels will gradually decline naturally. Interestingly, however, after pinpointing specific genetic markers for the condition, some experts now believe that low testosterone is genetic. Most of these low testosterone risk markers were located within the sex hormone-binding globulin (SHBG) gene, a type of protein that binds to testosterone. It is thought that increased levels of this protein could lead to decreased levels of testosterone in the blood.

How does the SHBG affect testosterone levels?

The SHBG gene plays a key role in regulating testosterone by encoding a protein that binds to sex hormones like testosterone and estradiol. SHBG primarily controls how much testosterone is bioavailable for use by the body. Variations in the SHBG gene can influence the levels of SHBG protein in the blood, affecting testosterone availability.

Testosterone in the bloodstream exists in two forms, bound and free. About 44% of testosterone is bound to SHBG, rendering it inactive. The remaining testosterone, especially the free and albumin-bound forms, is biologically active. Higher SHBG levels typically lead to less free testosterone, which can contribute to symptoms of low testosterone such as reduced libido, fatigue, and muscle loss.

Men who have three or more of these specific genetic risk markers are more than six times more likely to present low levels of testosterone when compared with men who don’t have any genetic markers at all. In a study group of more than 1,400 men, only around 1.5% presented three or more risk markers. It is thought that this scientific breakthrough could be used to help doctors identify men with a higher-than-average chance of developing low testosterone.

Genetic conditions that cause male hypogonadism (low testosterone)

Having a genetic variation associated with low testosterone doesn’t guarantee you’ll have low levels; it simply indicates a predisposition. However, some men experience low testosterone as a result of an underlying medical condition which is usually due to primary and secondary hypogonadism. In such cases, the likelihood of having low T is significantly higher. Here are some of those conditions:

Klinefelter’s syndrome

Two types of sex chromosomes (X and Y) determine a baby’s sex. Females have XX, while males have XY.

Babies born with Klinefelter’s syndrome have an extra X, meaning they have XXY chromosomes. Due to the presence of the Y chromosome, they are genetically male, but they experience some symptoms, such as reduced body and facial hair, enlarged breasts, and broad hips, due to the extra X. They also experience abnormal testes development, resulting in low testosterone and low sperm count. This genetic variation affects 1 in every 600 men.

Noonan syndrome

Noonan syndrome is caused by genetic mutations. A child can inherit it from his parents or develop it due to a spontaneous mutation. It causes developmental issues and reduced growth and sex hormone secretion in children. Men with Noonan syndrome usually have low testosterone and are infertile.

Kallmann syndrome

Kallmann syndrome is a rare genetic condition that occurs due to the underdevelopment of certain neurons, that make the hypothalamus (a part of the brain) release the gonadotropin-releasing hormone (GnRH). GnRH stimulates the pituitary gland to release luteinizing hormone (LH), which further stimulates the testes to secrete testosterone.

Men with Kallmann syndrome have GnRH deficiency and experience late or no puberty because their testes do not release enough testosterone. They may have undescended or partially descended testes and may stay infertile if they don’t receive hormone therapy.

Prader-Willi syndrome

Prada-Willi syndrome is another genetic variation that’s caused by the deletion of certain genes on chromosome 15. It causes various mental, physical and behavioural problems in affected individuals. Its common symptoms include sleep issues, poor sexual development, and mood changes.

Men suffering from this syndrome mostly have low testosterone levels. Testosterone replacement therapy (TRT) may help relieve their symptoms.

Myotonic dystrophy

Myotonic dystrophy is caused by mutations in chromosome Y. It can happen at any age but usually shows its symptoms when you are in your 20s or 30s. It causes muscle weakness in different body parts and leads to delayed development. Men with this condition have small testes and suffer from low T.

Other causes of low T

Research suggests there’s a genetic component to low testosterone levels. However, your environment can affect your levels too!

Obesity

Fat tissues tend to convert testosterone into oestrogen. That is why the build-up of fat in men leads to low T.

Lack of exercise and poor diet

An unhealthy diet coupled with a lack of exercise can contribute to weight gain and obesity, which are closely associated with low testosterone in men. This connection arises because fat tissue converts testosterone into estrogen. As body fat increases, this conversion process accelerates, leading to a decline in testosterone.

Medicine side effect

Certain medications, including antidepressants, anti-anxiety, statins, opioids, and hypertension medications, are known to lower serum testosterone levels in men.

If your low T is due to these medications, you should ask your doctor to prescribe a different medicine that does not influence testosterone.

Alcohol abuse

Consuming alcohol in large quantities can badly affect Leydig’s cells, which secrete testosterone, leading to low T. That is why doctors suggest low T patients restrict their alcohol intake.

Lack of sleep

Experts believe that a lack of quality sleep can negatively affect testosterone production.

In a study published in the Journal of the American Medical Association (JAMA), researchers observed the correlation between sleep and testosterone levels in participants. They found that healthy men who sleep 5 hours a day have 10% to 15% low T levels compared to healthy men who sleep 8 hours a day.

The impact of early childhood on testosterone levels

Research from Durham University suggests that a man’s testosterone levels are shaped more by his childhood environment than by genetics. Men who grew up in challenging conditions, such as in poverty or exposure to disease, are more likely to have lower levels than those from healthier environments.

While the causes of low testosterone remain unclear outside of natural ageing, symptoms such as reduced sperm production and muscle loss are treatable. It’s essential to consult a health professional if you experience symptoms, as not all cases require treatment. They can offer guidance to enhance your energy and overall quality of life.

How to tell if your testosterone levels are low?

Men experiencing low T symptoms are asked to have a serum testosterone test that calculates total testosterone, free testosterone, and bound testosterone levels in their blood. If 2 to 3 testosterone tests show your levels are below 300 ng/dL, your doctor will most likely declare you have low T.

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Testosterone Replacement Therapy (TRT)

Low T caused by genetic problems is mostly treated with TRT, in which you take testosterone from external sources to elevate your blood T levels.

There are different ways to administer exogenous testosterone, including injections, gels, pellets, patches, and capsules. Your doctor will select the one which best suits your needs. They will also go through all the risk factors associated with the treatment.

Testosterone therapy helps men with genetic problems improve their quality of life. It may reduce erectile dysfunction, improve libido, increase muscle mass, strengthen bones, and even improve your energy.

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Summing it up

Low T is caused by various factors, including habits, diseases, medications, etc. Studies indicate changes in your genes may also play a part in whether you develop low T.

Whether your low T is caused by genetics or other factors, testosterone treatment (TRT) is the best solution to getting your life back. Contact one of our specialised doctors today to assess your symptoms and explore your treatment options.

References/Further reading/Bibliography/Scientific studies 

Coviello, A.D., Haring, R., Wellons, M., Vaidya, D., Lehtimäki, T., Keildson, S., Lunetta, K.L., He, C., Fornage, M., Lagou, V. and Mangino, M., 2012. A genome-wide association meta-analysis of circulating sex hormone–binding globulin reveals multiple Loci implicated in sex steroid hormone regulation. PLoS genetics, 8(7), p.e1002805.

Jahangir Moini MD, MPH, … Raheleh Ahangari MD 2024. Klinefelter Syndrome. https://www.sciencedirect.com/topics/psychology/klinefelter-syndrome

Leproult R, Van Cauter E. Effect of 1 Week of Sleep Restriction on Testosterone Levels in Young Healthy Men. JAMA. 2011;305(21):2173–2174. doi:10.1001/jama.2011.710

Ohlsson, C., Wallaschofski, H., Lunetta, K.L., Stolk, L., Perry, J.R., Koster, A., Petersen, A.K., Eriksson, J., Lehtimäki, T., Huhtaniemi, I.T. and Hammond, G.L., 2011. Genetic determinants of serum testosterone concentrations in men. PLoS genetics, 7(10), p.e1002313.

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