What are the risks of testosterone (hormone replacement therapy) therapy?

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Last updated: April 25, 2025View editorial policy

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From the Guidelines

Testosterone therapy carries significant risks, including cardiovascular complications, and patients should be aware of these risks before starting treatment. The risks associated with testosterone therapy include cardiovascular events such as heart attack, stroke, and blood clots, particularly in men with existing heart disease 1. According to a study published in the Annals of Internal Medicine, the pooled risk for adverse cardiovascular outcomes did not differ significantly between testosterone and placebo groups, with a Peto OR of 1.22 [CI, 0.66 to 2.23] 1.

Key Risks and Considerations

  • Cardiovascular complications: The incidence of cardiovascular events was 2.3% in the testosterone group, compared with 1.5% in the placebo group 1.
  • Sleep apnea: Testosterone therapy can worsen sleep apnea, a condition that can increase the risk of cardiovascular disease and other health problems.
  • Prostate health: The therapy can stimulate noncancerous growth of the prostate (benign prostatic hyperplasia) and potentially stimulate growth of existing prostate cancer.
  • Testicular shrinkage and reduced sperm production: Testosterone therapy can cause testicular shrinkage and reduced sperm production, leading to infertility.
  • Skin problems: Common side effects include acne and oily skin, and some men experience breast enlargement (gynecomastia).
  • Fluid retention: The treatment can cause fluid retention, which may contribute to heart failure in susceptible individuals.

Monitoring and Administration

Regular monitoring through blood tests is essential during testosterone therapy to check hormone levels, red blood cell counts, and prostate-specific antigen levels to monitor prostate health 1. Patients typically receive testosterone through injections, daily transdermal patches or gels, or less commonly via oral medications or implantable pellets. The decision to start testosterone therapy should be individualized based on a patient's specific health status and needs, and the potential benefits and risks should be carefully weighed 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. Androgens may increase sensitivity to oral anticoagulants Carcinogenesis: Animal data Testosterone has been tested by subcutaneous injection and implantation in mice and rats. The implant induced cervical-uterine tumors in mice, which metastasized in some cases. Human data. There are rare reports of hepatocellular carcinoma in patients receiving long-term therapy with androgens in high doses. Geriatric patients treated with androgens may be at an increased risk of developing prostatic hypertrophy and prostatic carcinoma although conclusive evidence to support this concept is lacking.

The risks of testosterone therapy include:

  • Acute urethral obstruction in patients with benign prostatic hypertrophy
  • Priapism or excessive sexual stimulation
  • Oligospermia after prolonged administration or excessive dosage
  • Polycythemia (increased hemoglobin and hematocrit levels)
  • Increased serum cholesterol levels
  • Increased sensitivity to oral anticoagulants
  • Hepatocellular carcinoma (rare reports in patients receiving long-term therapy with androgens in high doses)
  • Prostatic hypertrophy and prostatic carcinoma (increased risk in geriatric patients, although conclusive evidence is lacking) 2

From the Research

Risks of Testosterone Therapy

The risks associated with testosterone therapy are numerous and have been documented in various studies 3, 4, 5, 6, 7. Some of the potential risks include:

  • Cardiovascular complications, as warned by the U.S. Food and Drug Administration 3
  • Rising prostate-specific antigen levels 3
  • Worsening lower urinary tract symptoms 3
  • Polycythemia 3, 4, 7
  • Increased risk of venous thromboembolism 3
  • Erythrocytosis 6, 7
  • Hyperviscosity 6
  • Liver toxicity 6
  • Worsening untreated sleep apnea or severe heart failure 6
  • Obstructive sleep apnea (OSA) 7
  • Urolithiasis 7
  • Benign prostatic hyperplasia (BPH) 6, 7

Monitoring and Precautions

It is essential to monitor patients receiving testosterone therapy to ensure that testosterone levels rise appropriately, clinical improvement occurs, and no complications develop 3. Physicians should discuss the potential benefits and risks of testosterone replacement therapy with patients before initiating treatment 3, 6. Additionally, patients with certain conditions, such as untreated prostate and breast cancer, should not receive testosterone replacement therapy 4.

Individualized Treatment

Testosterone therapy should be individualized, and comorbidities should be addressed 5. The decision to initiate testosterone therapy should be based on a thorough evaluation of the patient's symptoms, medical history, and laboratory results 3, 6.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Testosterone Therapy: Review of Clinical Applications.

American family physician, 2017

Research

Risks of testosterone replacement therapy in men.

Indian journal of urology : IJU : journal of the Urological Society of India, 2014

Research

Benefits and risks of testosterone therapy in older men.

Minerva urologica e nefrologica = The Italian journal of urology and nephrology, 2019

Research

The benefits and risks of testosterone replacement therapy: a review.

Therapeutics and clinical risk management, 2009

Research

Controversies in Testosterone Therapy.

Sexual medicine reviews, 2021

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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