What Are the Side Effects of Testosterone Replacement Therapy?

Hormonal changes

Normal testosterone metabolism results in the formation of two primary metabolites, namely, DHT and estradiol (E2, a form of estrogen).

Elevated levels of DHT can cause:

• Benign (noncancerous) growth of the prostate (benign prostatic hyperplasia)
• Increased oiliness of the skin and acne
• Male pattern balding

Abnormal increases in estradiol can lead to:

• Mood swings
• Breast tissue changes
• Fluid retention which may cause swelling or an increase in blood pressure
• Low testosterone levels, erectile dysfunction, and a decrease in free testosterone

Prostate changes

People with a first-degree relative diagnosed with prostate cancer, as well as those with an elevated prostate-specific antigen level, should proceed with caution and be closely monitored.

Treatment should not be considered for men who have a personal history of prostate cancer. TRT does not cause prostate cancer, but it is possible that elevated testosterone levels (even within the normal range) can cause an otherwise undetected prostate cancer lesion to grow more aggressively.

Fertility problems

When testosterone levels are restored, either naturally or through treatment, the brain reduces the stimulus to produce testosterone by secreting less gonadotropin-releasing hormone (GnRH).  Because this single hormone regulates both follicle-stimulating hormone and luteinizing hormone, the natural suppression of GnRH can reduce fertility. Furthermore, this process is responsible for the shrinkage and change in firmness in the testicles.

Erythrocytosis (increased RBC count)

According to studies, TRT causes increased RBC count that can make the blood more viscous. Hematocrit levels higher than 54.0% increase a person’s risk of:

• Abnormal clotting
• Spleen enlargement
• Heart failure 
• Other serious conditions

Increased risk of medical conditions

• Heart attack
• Hypertension
• Difficulty breathing
• Sleep apnea
• Edema
• Elevated hemoglobin and hematocrit
• Impaired cholesterol metabolism
• Blood clots
• Brain stroke
• Prostate disorders
• Live failure
• Liver cancer

The FDA requires that people should be made aware of the possibility of side effects, risks, and complications before and during TRT.

The FDA has approved testosterone replacement therapy (TRT) as a treatment method for men who lack or have low levels of testosterone in addition to an associated medical condition. If you have clinically low testosterone levels, using testosterone can improve your health, physical function, sexual performance, and overall well-being. 

Potential benefits of TRT include:

• Improved sex drive: Because testosterone regulates your sex drive, it's common to notice an increase in your level of interest in sex after starting TRT. You may notice that you are thinking about sex more frequently, getting aroused more easily, and having more sex with your partner. 
• Improved sexual function and erections: With TRT, some aspects of sexual function may improve. Studies report that TRT may improve erections in men with mild erectile dysfunction.
• Better mood and increased quality of life: According to studies, TRT improves mood parameters such as energy levels and positive feelings in men with clinically low testosterone levels.
• Increased muscle mass and bone density: TRT may result in muscle growth and strength gain, as well as increase average bone mineral density.

Testosterone replacement therapy can be administered in various ways:

• Transdermal testosterone skin patches: These are usually placed on your back, stomach, thighs, or upper arm. The patch slowly releases testosterone into your skin, where it is absorbed into your bloodstream.
• Topical testosterone gels: These gels contain testosterone, which is absorbed through the skin and into the bloodstream. When using testosterone gel, exercise caution because it can potentially spread to other people through close skin-to-skin contact, leading to mild side effects.
• Testosterone capsules: In some cases, your doctor may prescribe testosterone tablets or capsules. These frequently contain testosterone derivatives with a long half-life.
• Testosterone implants or testosterone pellets: These are placed beneath your skin. Most testosterone implants last 3-6 months before needing to be replaced.
• Intranasal testosterone: This is administered through the nose as a gel, allowing the testosterone to enter your bloodstream quickly.
• Testosterone injections: Your doctor may inject the medication in their office or instruct you on how to safely administer injectable testosterone at home.

Your doctor may ask you about your needs and preferences before recommending the best form of testosterone therapy for you. If you are uncomfortable with a particular type (for example, you dislike needles and would prefer not to use injectable medication), inform your doctor so that they can prescribe a different form of testosterone.

Negative side effects of testosterone replacement therapy (TRT) can be reduced by consulting a qualified physician about your risk factors and submitting to routine blood testing before, during, and after therapy to detect any complications before they become unmanageable. Again, always seek expert medical attention. 

Although TRT is generally safe for the majority of people, it does present a risk in select circumstances. By following your doctor's recommendations, you can reduce your exposure to the potential side effects of TRT while increasing the benefits.