At what levels of hypogonadism (low testosterone) is testosterone replacement therapy (TRT) indicated?

From the Guidelines

Testosterone replacement therapy is typically recommended when a man has consistently low testosterone levels (below 300 ng/dL) along with symptoms such as fatigue, decreased libido, erectile dysfunction, reduced muscle mass, or depression. Before starting treatment, two separate morning blood tests should confirm low testosterone levels 1. Common testosterone preparations include injections (testosterone cypionate or enanthate, 50-200mg every 1-2 weeks), daily transdermal gels (AndroGel, Testim, 50-100mg), patches (Androderm, 2-6mg daily), or pellets implanted subcutaneously (150-450mg every 3-6 months) 1. Oral testosterone is generally avoided due to liver toxicity concerns. Treatment should be monitored with testosterone level checks after 2-3 months, then annually, along with hematocrit, PSA, and liver function tests. Some key points to consider when evaluating testosterone levels include:

• The diagnosis of low testosterone should be made only after two total testosterone measurements are taken on separate occasions with both conducted in an early morning fashion 1.
• The clinical diagnosis of testosterone deficiency is only made when patients have low total testosterone levels combined with symptoms and/or signs 1.
• Clinicians should consider measuring total testosterone in patients with a history of unexplained anemia, bone density loss, diabetes, exposure to chemotherapy, exposure to testicular radiation, HIV/AIDS, chronic narcotic use, male infertility, pituitary dysfunction, and chronic corticosteroid use even in the absence of symptoms or signs associated with testosterone deficiency 1. Testosterone therapy works by replacing the hormone that the body is not producing adequately, helping restore normal physiological functions. Therapy is contraindicated in men with prostate or breast cancer, untreated severe sleep apnea, heart failure, or elevated hematocrit above 54% 1. It is essential to weigh the potential benefits and harms of testosterone treatment, as well as consider the patient's preferences and values 1. The American College of Physicians suggests that clinicians should reevaluate symptoms within 12 months and periodically thereafter, and discontinue testosterone treatment in men with age-related low testosterone with sexual dysfunction in whom there is no improvement in sexual function 1.

From the FDA Drug Label

Prior to initiating testosterone gel 1. 62%, confirm the diagnosis of hypogonadism by ensuring that serum testosterone concentrations have been measured in the morning on at least two separate days and that these serum testosterone concentrations are below the normal range. The testosterone levels to give testosterone are when the serum testosterone concentrations are below the normal range, confirmed by measuring serum testosterone in the morning on at least two separate days 2.

• The dose should be titrated based on the pre-dose morning serum testosterone concentration at approximately 14 days and 28 days after starting treatment or following dose adjustment.
• Key points to consider when giving testosterone:
  • Primary hypogonadism: testicular failure due to conditions such as cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome, orchiectomy, Klinefelter's syndrome, chemotherapy, or toxic damage from alcohol or heavy metals.
  • Hypogonadotropic hypogonadism: gonadotropin or luteinizing hormone-releasing hormone (LHRH) deficiency or pituitary-hypothalamic injury from tumors, trauma, or radiation.

From the Research

Testosterone Levels and Replacement Therapy

• Testosterone levels decrease as men age, and a serum total testosterone level of less than 300 to 350 ng/dL on two separate morning blood samples is considered a low level 3.
• To receive exogenous testosterone replacement therapy (TRT), patients should meet criteria for hypogonadism, which is defined as a low testosterone level and signs or symptoms of hypogonadism 3.
• The aim of testosterone replacement therapy (TRT) is to improve symptoms and signs of testosterone deficiency, including decreased libido, erectile dysfunction, depressed mood, anaemia, loss of muscle and bone mass, by increasing serum testosterone levels to physiologic range 4.

Indications for Testosterone Replacement Therapy

• TRT is indicated for men with hypogonadism, defined as a low serum testosterone in the presence of signs and symptoms 5.
• Symptomatic individuals who have no contraindications to TRT should be offered treatment 5.
• TRT has been shown to improve sexual activity, hypogonadal symptoms, and sexual desire in men with hypogonadism and low libido 6.

Monitoring and Follow-up

• Patients receiving TRT require close monitoring for adverse effects 3.
• TRT should be continued in individuals demonstrating an improvement in signs and symptoms, which may take 3 months to a year for maximum response 5.
• Long-term TRT has been shown to reduce fatigue in men with hypogonadism 7.

Formulations and Administration

• Numerous testosterone formulations are available, ranging from topical gels to intramuscular injections 3.
• The choice of formulation depends on factors such as cost and patient preference 3.
• The routes of delivery approved for use in the Western world include buccal, nasal, subdermal, transdermal, and intramuscular (IM) 4.