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Testosterone Replacement Therapy: 4 Points to Consider

Testosterone replacement therapy may not be what the doctor ordered
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Testosterone deficiency (TD) has been getting attention over the last few years. This is probably due to the increasing age of the male population, the heightened awareness by medical providers, and direct-to-consumer advertising in the media.

Coincidently, testosterone clinics have become commonplace, with millions of men worldwide receiving testosterone replacement therapy (TRT) to treat diminished libido and erectile dysfunction. Between 2001 and 2011, TRT prescriptions among men above 40 in the US have more than tripled, from 0.81% in 2001 to 2.91% in 2011. 

The prevalence rate of TD or hypogonadism in men aged 45 years and older is 38.7%, while a crude estimate of 5.6% has symptomatic androgen deficiency. But among these symptomatic men, only 12% are treated. 

While testosterone plays an essential role in typical masculine physical characteristics, such as muscle mass and strength and facial and body hair growth, serum testosterone (T) is expected to decline as men age, especially with unhealthy lifestyles. 

Data from the Massachusetts Male Ageing Study (MMAS) showed that men aged 40-79 had an annual decline in total free T of 0.8-1.6% and 1.7-2.8% per year, respectively. This report means that approximately 2.5% of men over 40 would have abnormally low T levels based on hormone levels alone. 

Although it is hard to ignore the benefits of TRT, especially in men diagnosed with primary hypogonadism, there is much debate regarding its risks and benefits. Thus, the increasing trend of testosterone use may not be what the doctor ordered. This article outlines three reasons why recommending TRT needs further patient education and counseling. 

What is testosterone replacement therapy (TRT)?

Testosterone replacement therapy (sometimes called androgen replacement therapy) is a widely used treatment for men with symptomatic testosterone deficiency or hypogonadism. Evidence suggests that TRT can provide substantial benefits, including improved strength and physical function, increased libido and energy level, better bone density, and cardioprotective effects. 

For people with hypogonadism, especially those unable to produce testosterone naturally, TRT acts as a supplement that replaces the low testosterone levels in their bodies. TRT is available in several forms, such as skin and mouth patches, gels, injections, and implants. These methods get testosterone into the blood directly, which decreases the adverse effects on the liver. 

Nowadays, TRT is becoming increasingly popular for non-medical use, including:

  • Enhancing sexual performance
  • Achieving higher energy levels
  • Building muscle mass for bodybuilding

However, despite TRT’s well-documented advantages, there are some caveats. Current evidence suggests that TRT has long-term adverse effects and may not provide any benefit beyond addressing the cause of TD, especially if there is a secondary reason.

Here are a few points to consider regarding the over-prescription of testosterone replacement therapy:

1. Testosterone therapy does not necessarily correlate with quality of life

There is an increased emphasis on having a reasonable quality of life (QoL), especially in old age, because it’s crucial for overall happiness and well-being. Most people want to live a lifestyle they enjoy and be comfortable with for as long as possible. 

Unfortunately, men with symptomatic hypogonadism may experience a lack of energy, impaired sex life, fatigue, and depression, all of which can affect their QoL. 

However, there are limited data correlating age-associated testosterone decline with quality of life issues. While it is clear that low T can lead to symptoms that can alter QoL, TRT may not be necessary for older men with asymptomatic low testosterone levels. 

Clinical hypogonadism is the only FDA-approved indication for testosterone therapy replacement in men. In 2015, the FDA issued a safety bulletin cautioning the use of TRT as a treatment for age-related low testosterone due to the possible increased risk of heart attack and stroke. 

In the Annals of Internal Medicine journal, the authors concluded that although TRT may provide a slight improvement in sexual functioning, there is little to no benefit for other common symptoms of aging, including physical functioning, energy, vitality, depressive symptoms, or cognition.

A recent study of 69 men aged 18 and 65 with Leydig cell insufficiency received routine TRT for twelve months. The results showed that TRT did not significantly improve symptoms of anxiety, depression, fatigue, sexual function, and overall quality of life compared to placebo. 

2. Testosterone therapy has side effects

The beneficial effects of TRT are rarely disputed and widely publicized but have been met recently with controversy. Several studies suggest that testosterone use comes with side effects and may be contraindicated or can worsen other medical conditions, such as:

Sleep Apnea

Testosterone therapy may worsen sleep apnea, a sleeping disorder in which breathing repeatedly stops and starts.
Photo by Emma Filer on Pexels.com

Studies regarding the association between TRT and obstructive sleep apnea (OSA) have mixed results. Some studies argue that testosterone levels do not directly cause or worsen OSA, while others have shown that TRT aggravates OSA by several physiologic mechanisms. 

Here’s an image that shows those physiologic mechanisms:


Sleep apnea is a disorder that interrupts your testosterone production, making you feel tired and groggy during the day, despite having a full night’s rest. Increasing your testosterone levels without addressing your sleep apnea may make it worse and increase the dangerous health risks.

Related: Here are other YHF articles about Sleep Apnea and Insomnia.

Cardiovascular Issues

While testosterone has cardio-protective and anti-inflammatory properties, there is also possible cardiovascular risk associated with testosterone supplementation, prompting the FDA to advise against using TRT in age-related hypogonadism. 

According to the American Journal of Medicine, men taking TRT for age-related TD are at an increased risk for transient ischemic attack, ischemic stroke, and myocardial infarction, particularly in the first couple of years. The study reported a crude incidence rate of 1.19 (1.11-1.27 per 100 people per year). 


Like low testosterone, it is common to encounter benign prostatic hyperplasia (BPH) as men age. While men with hypogonadism can benefit from testosterone supplementation, it may not be as safe for men with BPH. Prostate enlargement is one of the significant risk factors associated with TRT. This concern is due to the body’s ability to convert testosterone to dihydrotestosterone (DHT), which is known to stimulate an increase in prostate size.

One randomized trial found that middle-aged men who received testosterone supplementation for eight months had their prostate size increase by 12%. That said, men who have BPH symptoms and are receiving TRT may experience a worsening.

On the other hand, recent data have found that high serum T levels are associated with a reduced risk of BPH. But despite many studies on this topic, experts have yet to formulate a definitive conclusion. 

Related: Here’s another YHF article about Prostate Enlargement.

Prostate Cancer

Another known risk of TRT is prostate cancer. It comes as no surprise since androgen deprivation therapy remains a fundamental treatment for men with advanced prostate cancer. Because of the risks involved, experts recommend a clinical practice guideline for using TRT. 

Healthcare providers must exercise caution when prescribing testosterone supplementation in men who are high-risk patients. These patients include men with first-degree relatives with prostate cancer and African-Americans who have prostate-specific antigen (PSA) >3 ng/mL. 

Breast Cancer

There is no conclusive evidence suggesting testosterone can directly lead to the development of breast cancer. However, experts cannot overlook that high T levels may lead to increased aromatization of exogenous androgens into bioactive estradiol. It is an active derivative of estrogen that may stimulate breast tissue receptors and increases the risk of breast cancer. 

Furthermore, one study, although limited, has found a breast cancer incidence of 11% in 45 men on long-term TRT over ten years. Is it a small sample size? Yes, it is. And further research is needed, but the risk is there. Using TRT simply to increase libido may not be the best option.

Related: Here’s another YHF article about Breast Cancer Screening recommendations.

Other Effects of testosterone therapy

Misuse of testosterone can also lead to other adverse effects, such as:

3. Testosterone decline is a normal process of aging

Low testosterone levels tends to increase as men age
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According to the American Urology Association (AUA), blood testosterone levels below 300 ng/dL are considered low. However, some experts and healthcare providers disagree. They feel that 250 ng/dL must be the reasonable cut-off in support of diagnosing low T. 

The problem with age-related low serum testosterone is that normal levels vary considerably between individuals. The range of what is considered normal is so broad that it can be challenging to determine whether they are concerningly low or just a normal aging process.

Evidence suggests that testosterone levels decline with age in all men at approximately 1%-3% per year. In a 2001 study, researchers found the incidence rate of below-normal testosterone levels increased to over 20% of men over 60, 30% over 70, and 50% over 80 years of age. However, only 2% of the same age group experience symptomatic hypogonadism.

4. Consider the Whole System

A point to consider with testosterone replacement is that levels vary from certain behaviors and health conditions. Rather than simply treating a low level, it is important to consider the whole system. For instance, healthy behaviors can increase levels. High-intensity training improves total testosterone levels. Conditions such as chronic stress, sleep deprivation, and sleep apnea can decrease testosterone production.

Moreover, classic symptoms like reduced sexual desire, fewer spontaneous erections, decreased bone density, and depression may be caused by factors other than low testosterone. For example, low libido can result from psychiatric or medical conditions that are common in older men. Such conditions include coronary disease, renal failure, or men with eating disorders [Meuleman and Van Lankveld et al.]. Similarly, erectile dysfunction can result from a neurologic impairment, vascular insufficiency, or substance use [N Engl J Med 2007].

Related: Here’s a YHF article about 7 Risk Factors Causing Hypogonadism in Men.


Testosterone deficiency is a medical condition that can lead to quality of life issues. And there is no denying that testosterone therapy can help address them. But it is also true that testosterone levels will naturally drop as men get older and symptoms may not necessarily occur. It is important to not lose sight of the forest for the trees. Simply treating a low level may be a missed opportunity to exploring the causes.

The popular dogma surrounding testosterone supplementation is that it can promote youth and vitality even for older men who are otherwise healthy. Media adverts probably have something to do with such misinformation, which led to the increasing popularity and over prescription of TRT. 

But like any other medical treatment, TRT needs thorough consideration and patient education. Despite many studies, researchers have yet to establish clear benefits or side effects of testosterone use in the long term. So if you and your doctor are considering testosterone therapy, be sure that it is clear that no other problems exist and the benefits are worth the risks. 

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