What are the effects of hypogonadism (low testosterone) on men and the improvements seen with testosterone replacement therapy (TRT)?

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From the Guidelines

Low testosterone in men can cause significant morbidity, and testosterone replacement therapy may provide small improvements in sexual functioning and quality of life, particularly in older men without well-established medical conditions known to cause hypogonadism. According to a recent study published in the Annals of Internal Medicine 1, testosterone therapy may have little to no benefit for other common symptoms of aging. The study found that long-term efficacy and safety of testosterone treatment are unknown, and its use in men without established conditions that cause permanent testicular or hypothalamic–pituitary dysfunction is not well supported by evidence.

When considering testosterone replacement therapy, it is essential to evaluate the potential benefits and harms. Some men may experience improvements in energy levels, sexual function, and mood within weeks of starting treatment. Physical changes like increased muscle mass and decreased body fat typically develop over 3-6 months. Common replacement options include injections, topical gels, patches, or pellets implanted every 3-6 months. However, it is crucial to note that testosterone treatment is approved by the U.S. Food and Drug Administration (FDA) for replacement therapy for men with primary or secondary hypogonadism caused by disorders of the hypothalamus, pituitary gland, or testes, often classified as organic or classical hypogonadism.

Key points to consider when evaluating the use of testosterone replacement therapy include:

  • The level of baseline testosterone that prompts initiation of therapy varies widely, and substantial proportions of U.S. men who receive testosterone therapy do not have testosterone levels tested before initiation of therapy 1
  • Testosterone treatment may provide small improvements in sexual functioning and quality of life, but long-term efficacy and safety are unknown 1
  • Patients should have regular monitoring of testosterone levels, hematocrit, PSA, and liver function during treatment
  • Side effects may include acne, fluid retention, breast enlargement, sleep apnea, and potentially increased cardiovascular risks
  • Testosterone replacement should be avoided in men with prostate cancer, severe heart failure, or elevated red blood cell counts.

From the FDA Drug Label

Endogenous androgens are responsible for normal growth and development of the male sex organs and for maintenance of secondary sex characteristics These effects include growth and maturation of the prostate, seminal vesicles, penis, and scrotum; development of male hair distribution, such as beard, pubic, chest, and axillary hair; laryngeal enlargement, vocal cord thickening, and alterations in body musculature and fat distribution Androgens have been reported to increase protein anabolism and decrease protein catabolism. Nitrogen balance is improved only when there is sufficient intake of calories and protein Androgens are responsible for the growth spurt of adolescence and for eventual termination of linear growth, brought about by fusion of the epiphyseal growth centers.

The impact of low testosterone on a man includes:

  • Decreased growth and development of male sex organs
  • Loss of secondary sex characteristics, such as male hair distribution and deep voice
  • Decreased muscle mass and strength
  • Decreased bone density
  • Decreased libido
  • Fatigue and decreased energy
  • Mood changes, such as depression and anxiety

The improvements seen when starting on testosterone replacement therapy include:

  • Increased muscle mass and strength
  • Improved bone density
  • Increased libido
  • Improved mood and reduced fatigue
  • Improved overall quality of life 2, 3, 4

From the Research

Low Testosterone Impact on Men

  • Low testosterone levels can significantly impair a man's quality of life, leading to symptoms such as depression, decreased libido, erectile dysfunction, and loss of muscle and bone mass 5.
  • Men with low testosterone levels are more likely to suffer from cardiovascular events and develop insulin resistance 5.
  • Testosterone deficiency can also lead to decreased energy, lower urinary tract symptoms, and anaemia 5, 6.

Improvements with Testosterone Replacement Therapy

  • Testosterone replacement therapy (TRT) can significantly improve symptoms of testosterone deficiency, including depression, bone mineral density, energy, libido, erectile function, muscle mass, insulin resistance, and lower urinary tract symptoms 5, 6.
  • TRT can be administered safely to symptomatic hypogonadal men, with various routes of delivery available, including buccal, nasal, subdermal, transdermal, and intramuscular 6.
  • All approved testosterone replacement methods can restore normal serum testosterone concentrations and relieve symptoms in most hypogonadal men 7.
  • Daily subcutaneous testosterone therapy has been shown to be effective in increasing total testosterone, free serum testosterone, and direct free testosterone levels in men with testosterone deficiency 8.

Considerations for Testosterone Replacement Therapy

  • The decision to start TRT should be individualized, taking into account the unique characteristics of each patient and the potential risks and benefits 6, 9.
  • Clinicians should consider the patient's preference, medical history, and fertility desires when selecting a treatment modality 7, 9.
  • Monitoring of TRT is necessary to minimize risks and maximize benefits, with regular assessments of testosterone levels, liver function, and other health parameters 6, 9.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Male hormones and men's quality of life.

Current opinion in urology, 2016

Research

Testosterone replacement therapy.

Andrology, 2020

Research

Testosterone Replacement Therapy in Hypogonadal Men.

Endocrinology and metabolism clinics of North America, 2022

Research

Daily subcutaneous testosterone for management of testosterone deficiency.

Frontiers in bioscience (Elite edition), 2018

Research

Testosterone replacement therapy: For whom, when and how?

Metabolism: clinical and experimental, 2018

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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