What are the side effects of testosterone replacement therapy (TRT)?

From the Guidelines

Testosterone replacement therapy (TRT) can cause several serious side effects, including increased red blood cell production, fluid retention, and potential stimulation of existing prostate cancer, and therefore, patients should be closely monitored while on treatment.

Common Side Effects

• Acne
• Oily skin
• Increased body hair growth
• Male pattern baldness
• Fluid retention leading to swelling in the ankles and feet
• Breast enlargement (gynecomastia)
• Sleep apnea or worsening of existing sleep apnea

Serious Concerns

• Increased red blood cell production (polycythemia), which can thicken blood and increase stroke risk, requiring regular blood count monitoring 1
• Reduced sperm production and testicular size, potentially causing infertility
• Potential stimulation of growth of existing prostate cancer and worsening benign prostatic hyperplasia symptoms
• Cardiovascular risks, including increased risk of heart attack and stroke, particularly in older men with existing heart disease 1

Psychological Effects

• Mood swings
• Aggression
• Increased libido

Monitoring and Management

Regular monitoring through blood tests and physical exams is essential during TRT to manage these potential side effects effectively 1. Injections appear to be associated with a greater risk of erythrocytosis than topical preparations, and patients should be aware of this risk when choosing a formulation 1.

From the FDA Drug Label

Abuse-Related Adverse Reactions Serious adverse reactions have been reported in individuals who abuse anabolic androgenic steroids, and include cardiac arrest, myocardial infarction, hypertrophic cardiomyopathy, congestive heart failure, cerebrovascular accident, hepatotoxicity, and serious psychiatric manifestations, including major depression, mania, paranoia, psychosis, delusions, hallucinations, hostility and aggression. The following adverse reactions have also been reported in men: transient ischemic attacks, convulsions, hypomania, irritability, dyslipidemias, testicular atrophy, subfertility, and infertility The following additional adverse reactions have been reported in women: hirsutism, virilization, deepening of voice, clitoral enlargement, breast atrophy, male-pattern baldness, and menstrual irregularities. The following adverse reactions have been reported in male and female adolescents: premature closure of bony epiphyses with termination of growth, and precocious puberty

The testosterone replacement therapy side effects include:

• Cardiovascular events: cardiac arrest, myocardial infarction, hypertrophic cardiomyopathy, congestive heart failure, cerebrovascular accident
• Psychiatric manifestations: major depression, mania, paranoia, psychosis, delusions, hallucinations, hostility and aggression
• Men: transient ischemic attacks, convulsions, hypomania, irritability, dyslipidemias, testicular atrophy, subfertility, and infertility
• Women: hirsutism, virilization, deepening of voice, clitoral enlargement, breast atrophy, male-pattern baldness, and menstrual irregularities
• Adolescents: premature closure of bony epiphyses with termination of growth, and precocious puberty 2

From the Research

Testosterone Replacement Therapy Side Effects

• The side effects of testosterone replacement therapy (TRT) include polycythemia, peripheral edema, cardiac and hepatic dysfunction 3
• TRT has been associated with an increased risk of benign prostate hypertrophy (BPH), prostate cancer, gynecomastia, testicular atrophy, and infertility 4
• Other possible adverse effects associated with TRT include increased estrogen levels and gynecomastia, which are usually managed with aromatase inhibitors and tamoxifen 5
• Cardiovascular risks from TRT include hypertension and erythrocytosis, which mandate periodic hematocrit and blood pressure monitoring 5
• Therapeutic phlebotomy is indicated if the hematocrit exceeds 52% 5

Management of Side Effects

• Monitoring and management of adverse effects are critical to maximize benefit and minimize the risks of TRT 5
• Effective patient education and counseling are also essential to improve compliance and treatment outcomes 5
• The choice of formulation depends on factors such as cost and patient preference, and patients receiving this therapy require close monitoring 6
• Clinicians must consider the unique characteristics of each patient and make the necessary adjustments in the management of late-onset hypogonadism (LOH) in order to provide the safest and most beneficial results 7

Contraindications and Precautions

• TRT is contraindicated in men with untreated prostate and breast cancer 3
• TRT should not be administered to individuals with active evidence of untreated prostate cancer, except under rare circumstances such as active surveillance for very low-risk disease 5
• Older oral forms of TRT can affect liver function; therefore, transdermal, newer oral forms and injectables are generally favored in men with a history of liver disease 5