Is it safe to take testosterone (hormone replacement therapy) after the age of 40?

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Last updated: June 29, 2025View editorial policy

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From the Guidelines

Testosterone replacement therapy can be considered safe for men over 40 with age-related low testosterone and sexual dysfunction, but only when medically indicated and properly supervised, as suggested by the American College of Physicians in 2020 1. When considering testosterone replacement therapy, it's essential to weigh the potential benefits and harms. The American College of Physicians recommends discussing the initiation of testosterone treatment in men with age-related low testosterone and sexual dysfunction who want to improve sexual function 1. Key points to consider include:

  • The target patient population includes adult men with age-related low testosterone, which is characterized by a gradual decline in serum total testosterone levels beginning in men in their mid-30s 1.
  • Clinicians should reevaluate symptoms within 12 months and periodically thereafter, and discontinue testosterone treatment if there is no improvement in sexual function 1.
  • Intramuscular formulations may be considered over transdermal formulations due to lower costs and similar clinical effectiveness and harms 1.
  • Testosterone treatment should not be initiated to improve energy, vitality, physical function, or cognition in men with age-related low testosterone, as the evidence is low-certainty and conditional 1. It's crucial to approach testosterone replacement therapy with caution, considering the potential benefits and harms, and to prioritize regular monitoring and evaluation to ensure safe and effective treatment.

From the FDA Drug Label

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 safety of taking testosterone after the age of 40 is not explicitly confirmed by the FDA drug label. Key concerns for patients over 40 include:

  • Increased risk of prostatic hypertrophy
  • Possible increased risk of prostatic carcinoma, although conclusive evidence is lacking Given the potential risks and the lack of conclusive evidence supporting the safety of testosterone use in patients over 40, a conservative clinical decision would be to exercise caution when considering hormone replacement therapy in this age group 2.

From the Research

Safety of Testosterone Replacement Therapy Over 40

The safety of testosterone replacement therapy (TRT) for men over 40 years old has been a topic of discussion in the medical community. According to 3, testosterone therapy has been used for over 60 years to treat male hypogonadism, and it is generally accepted that men with low testosterone production will require androgen therapy.

Benefits and Risks of TRT

Studies have shown that TRT can produce a wide range of benefits for men with hypogonadism, including improvement in libido and sexual function, bone density, muscle mass, body composition, mood, erythropoiesis, cognition, quality of life, and cardiovascular disease 4. However, there are also potential risks associated with TRT, such as worsening symptoms of benign prostatic hypertrophy, liver toxicity, hyperviscosity, erythrocytosis, worsening untreated sleep apnea or severe heart failure 4.

Key Considerations for TRT

Some key points to consider when evaluating the safety of TRT for men over 40 include:

  • The presence of low testosterone levels and symptoms of hypogonadism are required for TRT indication 4
  • The potential benefits and risks of TRT should be discussed with the patient 4
  • Prostate safety is a major concern, and men with symptomatic lower urinary obstruction or suspected prostate cancer should be assessed carefully prior to androgen administration 5
  • Appropriate androgen administration with knowledgeable monitoring is generally safe and effective 5

Monitoring and Administration

Monitoring and administration of TRT are crucial to ensure safety and efficacy. According to 3, new application modes such as hydroalcoholic gel and intramuscular testosterone undecanoate have been shown to be effective and have fewer side effects compared to traditional methods. Additionally, 6 suggests that doses of testosterone up to five times physiologic replacement dose appear to have minimal risk of adverse psychosexual effects in the majority of normal men.

History and Clinical Uses of Testosterone Therapy

The history of testosterone therapy dates back to ancient times, with evidence of experimentation with mammalian testicles and claims of improved energy, erectile function, and urination 7. Today, there are clear and appropriate clinical uses of testosterone set by the American Urological Association to treat clinically significant testosterone deficiency 7.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Testosterone therapy--what, when and to whom?

The aging male : the official journal of the International Society for the Study of the Aging Male, 2004

Research

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

Therapeutics and clinical risk management, 2009

Research

Monitoring androgen replacement therapy: testosterone and prostate safety.

Journal of endocrinological investigation, 2005

Research

History of testosterone therapy through the ages.

International journal of impotence research, 2022

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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