Testosterone Replacement Therapy for Men: Risks and Benefits

By Chloe Bennett, B.Sc.Reviewed by Dr. Jennifer Logan, MD, MPH

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• What is Testosterone Replacement Therapy?
• What are the Benefits of TRT?
• What are the Risks of TRT?

Testosterone plays a vital role in the human body. Its effects increase muscle and bone strength and density, induce hematopoiesis, and drive libido and sexual function. Testicular production of testosterone typically declines with age, which can result in its beneficial effects being diminished. Testosterone replacement therapy (TRT) has been used as a treatment method to address low levels of testosterone in men, but what are the benefits, and are there any consequences?

What is Testosterone Replacement Therapy?

Testosterone replacement therapy (TRT) is approved by the United States Food and Drug Administration as a treatment method for men who lack or have low levels of testosterone alongside an associated medical condition. Late-onset hypogonadism (LOH) is one such condition which necessitates the use of TRT and due to an increasingly aged population, has increased in prevalence in recent years.

Late-onset hypogonadism is classified as a clinical and biochemical syndrome whereby there is a decrease in serum testosterone produced by the testes. Men with LOH can experience a range of symptoms including an increase in body fat, depressive or low mood, decrease in libido, a reduction in muscle mass and strength, and a decrease in bone density which can lead to the onset of osteoporosis.

The administration of TRT is used to restore serum testosterone levels to an appropriate physiological range for the patient’s age, and to improve symptoms in hypogonadal men. TRT is currently classified by route of administration which includes intramuscular, transdermal, nasal, buccal, and subdermal. Like all prescription medications, TRT is considered to have a range of beneficial effects alongside adverse effects which should be communicated with patients seeking to undergo treatment.

What are the Benefits of TRT?

Research has highlighted a range of health benefits that can develop by increasing levels of testosterone through TRT.

Cardiac Health

Research has found a link between the onset of cardiovascular disease and testosterone levels. A longitudinal study following 3,518 men over 17 years, found that men with low levels of testosterone were twice as likely to die due to cardiovascular disease than those with normal or expected levels of serum testosterone.

Subsequent research has found that even in middle-aged patients, having higher levels of testosterone was linked to good cardiovascular health profiles; higher levels of high-density lipoprotein cholesterol, and low levels of insulin, systolic blood pressure and triglycerides.

Based on this body of literature, it could be suggested that men with low testosterone levels may be more at risk of developing cardiovascular problems, and as a result, may improve their cardiac health by undergoing TRT.

Increase in Muscle Mass

One of the well-researched adverse effects of low serum testosterone is a decrease in muscle mass and strength, which can negatively affect mobility. Research investigating the impact of TRT in a group of hypogonadal men found that TRT administration was able to reverse some of the aforementioned effects to some extent. An increase in lipid oxidation and muscle mass was observed and resulted in an improvement in overall lean body mass. Many patients reported that these effects boosted their quality of life, especially those that had limited mobility.

Increase in Mood

The relationship between mood disorders such as depression and low levels of testosterone have been found to be significant in older men. One study found that up to two-thirds of men with treatment-resistant depressive symptoms also had low testosterone. Furthermore, analysis of depressive symptom scores in men from the general population found that those with testosterone deficiency reported higher symptom scores, especially with regards to anxiety. Use of TRT could, therefore, be beneficial in reducing the prevalence or severity of mood disorders such as depression which may have gone on to develop in men with low testosterone without TRT as an intervention.

What are the Risks of TRT?

Research has found a range of potential adverse effects of undergoing TRT.

The Effects on the Prostate

Arguably, one of the major adverse effects of TRT is on the prostate. The human prostate is considered to be an androgen-dependent gland. Therefore, the use of anti-androgen agents in individuals with benign prostatic hyperplasia (BPH) can result in a decrease in prostate volume.

There have been a plethora of studies highlighting the potential consequences of using testosterone in patients with BPH.

Furthermore, a current prostate cancer diagnosis or history of prostate cancer is often a contraindication of TRT, as prostate tumor growth is stimulated by testosterone. Indeed, treatment for some forms of prostate cancer includes drugs to decrease testosterone levels in the body. Since the release of seminal work highlighting the effect of castration on prostate cancer, there have been concerns that the use of exogenous testosterone could be linked to the onset of prostate cancer and growth. Related studies have shown a worsening of cancer growth and symptoms in patients taking testosterone.

It is important to note that there has been conflicting research regarding the effects of exogenous testosterone on the prostate.

Dermatological Issues

An increase in serum levels of testosterone has been positively correlated with an increase in sebum secretion, which can lead to the development of acne. Despite this adverse effect to be considered minimal, it has been reported that up to 60% of those using intramuscular and topical forms of testosterone may also experience skin reactions, including pruritus and erythema.

Breast Pain and Enlargement

TRT can cause a range of physical and external changes in its users. Use of exogenous testosterone has been linked to an imbalance in the hypothalamic-pituitary axis, which can result in the conversion of testosterone to estrogen by a process called aromatization. If excessive amounts of estrogen are produced, this can lead to the development of breast pain or gynecomastia.

Liver damage

Research has found an association with the use of endogenous testosterone and hepatic diseases. Specifically, those undergoing TRT are more likely to develop hepatic failure, hepatotoxicity, intrahepatic cholestasis, and malignant and benign liver disease.

Like all medications, TRT has a range of health benefits induced by increasing the levels of testosterone within the male body. Any adverse complications should be thoroughly discussed with patients, and medical professions should check for their development.

Further Reading

• All Testosterone Content
• Testosterone Physiological Effects
• Testosterone Biochemistry
• Testosterone - What is Testosterone?
• Testosterone Mechanism