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

From the Guidelines

Testosterone supplements can have severe adverse effects, including increased risk of cardiovascular events, and users should be cautious when considering treatment. The most recent and highest quality study, published in 2020 in the Annals of Internal Medicine 1, found that the pooled risk for adverse cardiovascular outcomes did not differ significantly between testosterone and placebo groups, but the incidence of cardiovascular events was 2.3% in the testosterone group compared to 1.5% in the placebo group. Common side effects of testosterone supplements include acne, fluid retention, increased red blood cell production, breast enlargement (gynecomastia), and testicular shrinkage with reduced sperm production. More serious risks include worsening of sleep apnea, liver problems, and potential cardiovascular complications such as increased risk of heart attack and stroke.

Some key points to consider when evaluating the risks of testosterone supplements include:

• The certainty of evidence for primary harm outcomes, including cardiovascular events, is low, as reported in the 2020 study 1.
• The risk of serious adverse events, such as cardiovascular events, is a concern, and users should be monitored closely, as suggested by the 2020 study 1.
• The potential for testosterone supplements to worsen existing prostate conditions, potentially raising PSA levels and accelerating the growth of existing prostate cancer, is a concern, as noted in the 2004 study 1.
• Mood changes, including increased aggression, irritability, and mood swings, are common, and users should be aware of these potential effects, as reported in the 2004 study 1.
• Blood monitoring is essential during treatment, typically checking testosterone levels, complete blood count, liver function, and PSA every 3-6 months, as recommended by the 2004 study 1.

Overall, the potential risks of testosterone supplements, including cardiovascular events and other serious adverse effects, should be carefully considered before starting treatment, and users should be closely monitored to minimize these risks, as suggested by the 2020 study 1.

From the FDA Drug Label

The following adverse reactions in the male have occurred with some androgens: Endocrine and urogenital: Gynecomastia and excessive frequency and duration of penile erections. Oligospermia may occur at high dosages. Skin and appendages: Hirsutism, male pattern of baldness, seborrhea, and acne Fluid and electrolyte disturbances: Retention of sodium, chloride, water, potassium, calcium, and inorganic phosphates. Gastrointestinal: Nausea, cholestatic jaundice, alterations in liver function tests, rarely hepatocellular neoplasms and peliosis hepatis (see WARNINGS) Hematologic: Suppression of clotting factors II, V, VII, and X, bleeding in patients on concomitant anticoagulant therapy, and polycythemia. Nervous system: Increased or decreased libido, headache, anxiety, depression, and generalized paresthesia. Allergic: Hypersensitivity, including skin manifestations and anaphylactoid reactions. Miscellaneous: Inflammation and pain at the site of intramuscular injection. Patients with benign prostatic hypertrophy may develop acute urethral obstruction. Priapism or excessive sexual stimulation may develop. Oligospermia may occur after prolonged administration or excessive dosage.

The adverse effects of testosterone supplements include:

• Endocrine and urogenital effects: gynecomastia, excessive frequency and duration of penile erections, oligospermia
• Skin and appendages effects: hirsutism, male pattern of baldness, seborrhea, acne
• Fluid and electrolyte disturbances: retention of sodium, chloride, water, potassium, calcium, and inorganic phosphates
• Gastrointestinal effects: nausea, cholestatic jaundice, alterations in liver function tests, hepatocellular neoplasms, peliosis hepatis
• Hematologic effects: suppression of clotting factors, bleeding, polycythemia
• Nervous system effects: increased or decreased libido, headache, anxiety, depression, generalized paresthesia
• Allergic reactions: hypersensitivity, skin manifestations, anaphylactoid reactions
• Miscellaneous effects: inflammation and pain at the site of intramuscular injection, acute urethral obstruction, priapism, excessive sexual stimulation 2, 2

From the Research

Adverse Effects of Testosterone Supplements

• The use of testosterone supplements has been associated with several adverse effects, including mild and reversible acne and hirsutism, as well as changes to the lipid profile with oral, but not transdermal testosterone 3.
• Testosterone therapy has also been linked to an increased risk of hepatotoxicity, endometrial hyperplasia, and behavioral hostility, although short-term studies have shown no significant increase in these risks 3.
• Additionally, testosterone supplements can suppress fertility in men, leading to the use of alternative therapies such as selective estrogen receptor modulators (SERMs) 4.
• The use of testosterone supplements has also been linked to cardiovascular effects, including changes in blood pressure, blood viscosity, arterial vascular reactivity, hypercoagulable states, and polycythemia, although the evidence is mixed 5.
• Other potential adverse effects of testosterone supplements include breast cancer risk, although the evidence is mixed, with some studies suggesting a decrease in estrogen-induced breast epithelial proliferation with low-dose testosterone 3.

Alternative Therapies

• Clomiphene citrate has been shown to be an effective therapy for improving both biochemical and clinical symptoms of males suffering from hypogonadism, with few reported side effects and good safety aspects 6, 7.
• Enclomiphene, a trans-isomer of clomiphene citrate, has been shown to increase testosterone levels while stimulating FSH and LH production, without the undesirable effects attributable to zuclomiphene 4.
• Clomiphene citrate has also been shown to be effective in stimulating the endogenous production of testosterone, with a lower level of total cholesterol verified after three months of treatment 6.

Monitoring and Safety

• Individuals treated with testosterone supplements require monitoring for adverse effects, including cardiovascular effects, hepatotoxicity, and endometrial hyperplasia 3, 5.
• Further studies are needed to determine the impact of testosterone supplements on cardiovascular health and to establish the long-term safety of testosterone therapy 3, 5.