What level of hypogonadism (testosterone deficiency) warrants testosterone replacement therapy (TRT) via injection?

From the Guidelines

Testosterone replacement therapy is typically considered when a man's total testosterone level falls below 300 ng/dL (10.4 nmol/L), especially when accompanied by symptoms of low testosterone. This recommendation is based on the most recent and highest quality study available, which was published in 2020 by the American College of Physicians 1. The study found that testosterone therapy may provide small improvements in sexual functioning and quality of life in older men with low testosterone levels, but long-term efficacy and safety are unknown.

Key Considerations for Testosterone Replacement Therapy

• The level of baseline testosterone that prompts initiation of therapy varies widely, but a common threshold is a total testosterone level below 300 ng/dL (10.4 nmol/L) 1.
• Symptoms of low testosterone, such as fatigue, reduced libido, erectile dysfunction, decreased muscle mass, and mood changes, should also be taken into account when considering therapy.
• Treatment should be individualized based on symptom response and laboratory monitoring, with the goal of maintaining testosterone levels in the mid-normal range (500-600 ng/dL).
• Before starting therapy, two separate morning testosterone measurements should confirm low levels, and a comprehensive evaluation should rule out contraindications such as prostate cancer, severe sleep apnea, or erythrocytosis.

Monitoring and Follow-up

• Patients should have testosterone levels, hematocrit, and PSA monitored periodically, with the first follow-up typically occurring 3-6 months after starting treatment.
• The efficacy and safety of testosterone treatment in men without established conditions that cause permanent testicular or hypothalamic–pituitary dysfunction are still being studied, and long-term effects are unknown 1.
• The American College of Physicians recommends that testosterone therapy be used with caution and only when the benefits outweigh the potential risks, as the evidence for its use in men with low testosterone levels is still limited 1.

From the Research

Testosterone Levels and Replacement Therapy

• A serum total testosterone level of less than 300 to 350 ng/dL on two separate morning blood samples is considered a low level, according to 2.
• The 2018 American Urological Association guidelines recommend using 300 ng/dL as the threshold for prescribing testosterone replacement therapy (TRT) 3.
• However, some studies suggest that age-specific normative values and cutoffs should be integrated into the evaluation of young men presenting with testosterone deficiency, as young men have different testosterone reference ranges than older men 4.

Indications for Testosterone Replacement Therapy

• Patients should meet criteria for hypogonadism, which is defined as a low testosterone level and signs or symptoms of hypogonadism, to receive exogenous testosterone replacement therapy (TRT) 2.
• Signs and symptoms of hypogonadism may include low libido, lack of energy, and erectile dysfunction 3.
• Testosterone replacement therapy can be administered through various formulations, including topical gels, patches, oral tablets, and intramuscular injections 5.

Formulations and Efficacy

• Different formulations of testosterone may have varying effects on hematocrit levels, with intramuscular testosterone cypionate/enanthate associated with a significantly higher increase in mean hematocrit compared to patch 5.
• Changing testosterone gel preparations among suboptimally responsive hypogonadal men may improve clinical and biochemical responsiveness 6.
• The choice of formulation depends on factors such as cost, patient preference, and potential side effects 2, 6.