What are the risks of elevated testosterone levels during testosterone (T) supplementation?

From the Guidelines

High testosterone supplementation can lead to several health risks, including cardiovascular problems, hormonal imbalances, and fertility issues, and individuals should prioritize maintaining total testosterone levels within the normal range of 300-1000 ng/dL to minimize these risks. Excessive testosterone levels may cause cardiovascular problems, including increased risk of heart attack and stroke due to elevated red blood cell production (polycythemia), higher blood pressure, and unfavorable cholesterol changes 1. Hormonal imbalances can occur as the body converts excess testosterone to estrogen, potentially causing gynecomastia (breast tissue development in men) 1. Supplementation often suppresses natural testosterone production, which can lead to testicular shrinkage and fertility problems. Other dangers include liver damage (particularly with oral steroids), mood disturbances including aggression and depression, sleep apnea, acne, accelerated male pattern baldness, and potential prostate issues.

Some key points to consider when supplementing with testosterone include:

• Regular blood tests to monitor levels, hematocrit, liver function, cholesterol, and PSA (prostate-specific antigen) 1
• Ideal total testosterone levels should remain within the normal range of 300-1000 ng/dL, as exceeding this range significantly increases health risks 1
• If supplementing under medical supervision, follow prescribed dosages exactly and report any concerning symptoms immediately to your healthcare provider
• Evidence from 20 observational studies with a mean follow-up ranging from 0.73 to 10.3 years showed no increased risk for mortality, cardiovascular events, prostate cancer, or pulmonary embolism or deep venous thrombosis, but long-term safety evidence is lacking 1

It is essential to weigh the potential benefits and risks of testosterone supplementation and consider individual circumstances, such as age-related low testosterone, before starting treatment. The most recent and highest-quality study, published in 2020 in the Annals of Internal Medicine, provides guidance on testosterone treatment in adult men with age-related low testosterone, emphasizing the importance of careful consideration and monitoring 1.

From the FDA Drug Label

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. Hemoglobin and hematocrit levels (to detect polycythemia) should be checked periodically in patients receiving long-term androgen administration. Serum cholesterol may increase during androgen therapy. There are rare reports of hepatocellular carcinoma in patients receiving long-term therapy with androgens in high doses.

The dangers of high testosterone levels when supplementing include:

• Acute urethral obstruction in patients with benign prostatic hypertrophy
• Priapism or excessive sexual stimulation
• Oligospermia after prolonged administration or excessive dosage
• Polycythemia, which can be detected by checking hemoglobin and hematocrit levels
• Increased serum cholesterol levels
• Rare reports of hepatocellular carcinoma in patients receiving long-term therapy with androgens in high doses 2

From the Research

Dangers of High Testosterone Levels

• High testosterone levels can lead to increased hematocrit, which is a clinical concern that warrants further study 3
• Testosterone therapy can result in statistically significant increases in mean hematocrit, with varying degrees of increase depending on the formulation used 3
• Intramuscular testosterone cypionate/enanthate are associated with a significantly higher increase in mean hematocrit compared to patch formulations 3

Comparison of Testosterone Formulations

• Intranasal testosterone gel does not appear to significantly affect hematocrit levels, whereas intramuscular testosterone cypionate results in a significant increase in hematocrit 4
• Subcutaneous testosterone enanthate autoinjector is associated with lower post-therapy estradiol and hematocrit levels compared to intramuscular testosterone cypionate 5

Risks of Testosterone Supplementation

• Off-label use and misuse of testosterone supplements can carry known and unknown risks, including increased hematocrit and estradiol levels 6
• Testosterone supplementation should be used with caution, particularly in men with age-associated hypogonadism, and under the guidance of a healthcare professional 7

Testosterone Therapy and Hematocrit

• Testosterone therapy can lead to increased hematocrit, which can be a concern for men with pre-existing cardiovascular conditions 3, 4, 5
• The choice of testosterone formulation can affect the degree of hematocrit increase, with some formulations resulting in higher increases than others 3, 4, 5