What are the side effects of testosterone (testosterone) supplementation?

From the Guidelines

Testosterone Supplement Side Effects

Testosterone supplement side effects may include acne, gynecomastia, and increased risk of cardiovascular events, particularly with high-dose therapy exceeding 300mg of testosterone enanthate or cypionate per week 1. Prolonged use of testosterone supplements, typically beyond 12-18 months, may also lead to testicular atrophy, infertility, and polycythemia. Additionally, doses above 400mg per week have been associated with increased liver enzyme activity and potential hepatotoxicity, highlighting the need for careful monitoring and dose adjustment to minimize adverse effects 1.

Key Side Effects to Consider

• Cardiovascular events: The risk of cardiovascular events, such as myocardial infarction and stroke, may be increased with high-dose testosterone therapy 1.
• Testicular atrophy: Prolonged use of testosterone supplements can lead to testicular atrophy, which can result in infertility 1.
• Polycythemia: Testosterone therapy can increase red blood cell count, leading to polycythemia, which can increase the risk of blood clots and other cardiovascular events 1.
• Liver enzyme activity: High doses of testosterone can increase liver enzyme activity, which can indicate potential liver damage 1.
• Gynecomastia: Testosterone therapy can cause gynecomastia, which is the growth of breast tissue in men 1.
• Acne: Testosterone therapy can cause acne, particularly in high doses 1.
• Sleep apnea: Testosterone therapy can increase the risk of sleep apnea, particularly in older men 1.
• Prostate cancer: The risk of prostate cancer is unclear, but testosterone therapy may increase the risk of prostate cancer in some men 1.

Monitoring and Dose Adjustment

To minimize the risk of adverse effects, careful monitoring and dose adjustment are necessary. This includes regular check-ups with a healthcare provider, monitoring of liver enzyme activity, and adjustment of the dose as needed to minimize the risk of adverse effects 1.

From the FDA Drug Label

WARNINGS In patients with breast cancer and in immobilized patients, androgen therapy may cause hypercalcemia by stimulating osteolysis. In patients with cancer, hypercalcemia may indicate progression of bony metastasis. If hypercalcemia occurs, the drug should be discontinued and appropriate measures instituted Prolonged use of high doses of androgens has been associated with the development of peliosis hepatis and hepatic neoplasms including hepatocellular carcinoma (see PRECAUTIONS, Carcinogenesis). Peliosis hepatis can be a life-threatening or fatal complication If cholestatic hepatitis with jaundice appears or if liver function tests become abnormal, the androgen should be discontinued and the etiology should be determined. Drug-induced jaundice is reversible when the medication is discontinued. Geriatric patients treated with androgens may be at an increased risk for the development of prostatic hypertrophy and prostatic carcinoma There have been postmarketing reports of venous thromboembolic events, including deep vein thrombosis (DVT) and pulmonary embolism (PE), in patients using testosterone products, such as testosterone enanthate injection. Evaluate patients who report symptoms of pain, edema, warmth and erythema in the lower extremity for DVT and those who present with acute shortness of breath for PE If a venous thromboembolic event is suspected, discontinue treatment with testosterone enanthate injection and initiate appropriate workup and management. Long term clinical safety trials have not been conducted to assess the cardiovascular outcomes of testosterone replacement therapy in men To date, epidemiologic studies and randomized controlled trials have been inconclusive for determining the risk of major adverse cardiovascular events (MACE), such as non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death, with the use of testosterone compared to non-use Some studies, but not all, have reported an increased risk of MACE in association with use of testosterone replacement therapy in men. Patients should be informed of this possible risk when deciding whether to use or to continue to use testosterone enanthate injection Testosterone has been subject to abuse, typically at doses higher than recommended for the approved indication and in combination with other anabolic steroids. Anabolic androgenic steroid abuse can lead to serious cardiovascular and psychiatric adverse reactions (see DRUG ABUSE AND DEPENDENCE) If testosterone abuse is suspected, check serum testosterone concentrations to ensure they are within therapeutic range. However, testosterone levels may be in the normal or subnormal range in men abusing synthetic testosterone derivatives. Counsel patients concerning the serious adverse reactions associated with abuse of testosterone and anabolic steroids Conversely, consider the possibility of testosterone and anabolic steroid abuse in suspected patients who present with serious cardiovascular or psychiatric adverse events. Due to sodium and water retention, edema with or without congestive heart failure may be a serious complication in patients with preexisting cardiac, renal, or hepatic disease In addition to discontinuation of the drug, diuretic therapy may be required. If the administration of testosterone enanthate is restarted, a lower dose should be used. Gynecomastia frequently develops and occasionally persists in patients being treated for hypogonadism. Androgen therapy should be used cautiously in healthy males with delayed puberty The effect on bone maturation should be monitored by assessing bone age of the wrist and hand every six months. In children, androgen treatment may accelerate bone maturation without producing compensatory gain in linear growth. This adverse effect may result in compromised adult stature. The younger the child the greater the risk of compromising final mature height.

DRUG ABUSE AND DEPENDENCE Controlled Substance Testosterone enanthate contains testosterone, a Schedule III controlled substance in the Controlled Substances Act. Abuse Drug abuse is intentional non-therapeutic use of a drug, even once, for its rewarding psychological and physiological effects. Abuse and misuse of testosterone are seen in male and female adults and adolescents Testosterone, often in combination with other anabolic androgenic steroids (AAS), and not obtained by prescription through a pharmacy, may be abused by athletes and bodybuilders. There have been reports of misuse of men taking higher doses of legally obtained testosterone than prescribed and continuing testosterone despite adverse events or against medical advice 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 Because these reactions are reported voluntarily from a population of uncertain size and may include abuse of other agents, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure

The side effects of testosterone supplementation include:

• Cardiovascular events: deep vein thrombosis (DVT), pulmonary embolism (PE), myocardial infarction, stroke, and cardiovascular death 2
• Hepatic events: peliosis hepatis, hepatic neoplasms, hepatocellular carcinoma, cholestatic hepatitis, and jaundice 2
• Psychiatric events: major depression, mania, paranoia, psychosis, delusions, hallucinations, hostility, and aggression 2
• Endocrine events: gynecomastia, testicular atrophy, subfertility, and infertility 2 2
• Other events: edema, congestive heart failure, sodium and water retention, and compromised adult stature in children 2 It is essential to monitor patients for these potential side effects and adjust the treatment regimen accordingly. Patients should be informed of the possible risks associated with testosterone supplementation, particularly the risk of major adverse cardiovascular events (MACE) 2.

From the Research

Side Effects of Testosterone Supplementation

The side effects of testosterone supplementation can be significant and varied. Some of the known side effects include:

• Erythrocytosis, which is an increase in red blood cell count, and can lead to high blood viscosity and increased risk of vascular complications 3
• Cardiovascular-related events, such as heart attacks and strokes, which have been shown to be increased in men taking testosterone therapy 4
• Acne and hirsutism, which are common side effects of testosterone therapy in women 5
• Changes to the lipid profile, including decreases in high-density lipoprotein cholesterol 6
• Gynecomastia and prostate problems, which have been reported in some men taking testosterone enanthate 6
• Weight gain and fatigue, which are common side effects of testosterone therapy 6

Population-Specific Side Effects

Some side effects of testosterone supplementation may vary between population groups. For example:

• Chinese men may experience increases in liver transaminases, while non-Chinese men may not 6
• Non-Chinese men may experience decreases in high-density lipoprotein cholesterol, while Chinese men may not 6

Reversibility of Side Effects

Many of the side effects of testosterone supplementation have been shown to be reversible. For example:

• The effects of testosterone enanthate on skin, muscle, liver, lipid metabolism, and hemopoietic functions were reversible within 6 months of stopping injections 6
• The increases in red blood cell count and hemoglobin caused by testosterone therapy can be reversed by stopping the therapy or switching to a different formulation 3