What are the adverse effects of testosterone (testosterone) therapy?

From the Guidelines

Testosterone therapy is not associated with an increased risk of mortality, cardiovascular events, prostate cancer, or pulmonary embolism, according to the most recent evidence from 2020 1. The potential side effects of testosterone therapy include acne, fluid retention, and increased red blood cell count, but the evidence suggests that these risks are not significantly increased with testosterone treatment 1. Some key points to consider when evaluating the side effects of testosterone therapy include:

• The lack of consistent differences in harms according to transdermal versus intramuscular formulations 1
• The importance of patient preferences, with some studies suggesting that patients prefer injectable testosterone over gel-based pellet regimens due to lower cost, while others prefer topical gel for convenience and ease of use 1
• The need for regular monitoring through blood tests to check hormone levels, red blood cell counts, cholesterol, and liver function 1 The American College of Physicians suggests that clinicians discuss the potential benefits, harms, costs, and patient's preferences when considering testosterone treatment, and reevaluate symptoms within 12 months and periodically thereafter 1. It is essential to weigh the potential benefits and risks of testosterone therapy, considering the individual patient's preferences and values, as well as the clinical guidelines and evidence-based recommendations 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 side effects of testosterone 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
• Effects in men: transient ischemic attacks, convulsions, hypomania, irritability, dyslipidemias, testicular atrophy, subfertility, and infertility
• Effects in women: hirsutism, virilization, deepening of voice, clitoral enlargement, breast atrophy, male-pattern baldness, and menstrual irregularities
• Effects in adolescents: premature closure of bony epiphyses with termination of growth, and precocious puberty 2 2

From the Research

Side Effects of Testosterone

• The provided studies do not directly discuss the side effects of testosterone, but rather the treatment of hypogonadism using human chorionic gonadotropin (hCG) or testosterone replacement therapy (TRT) 3, 4, 5, 6, 7.
• However, it can be inferred that the side effects of testosterone replacement therapy may include increased risk of infertility, as hCG therapy is often used as an alternative to TRT due to its ability to trigger testosterone and sperm production without the negative effects on fertility 4, 5.
• The Endocrine Society's clinical practice guideline for testosterone therapy in men with hypogonadism recommends against starting testosterone therapy in patients with certain conditions, such as breast or prostate cancer, palpable prostate nodule or induration, and elevated hematocrit, suggesting that these may be potential side effects of testosterone therapy 6.
• The studies on hCG monotherapy for the treatment of hypogonadal symptoms in men with total testosterone > 300 ng/dL reported no adverse events or side effects, suggesting that hCG therapy may be a safer alternative to TRT in certain cases 3, 7.