What is the proper protocol for prescribing testosterone (T) therapy?

From the Guidelines

Testosterone replacement therapy should be prescribed with caution, considering the potential benefits and risks, and only after confirming hypogonadism with two morning total testosterone measurements below 300 ng/dL along with symptoms, as recommended by the American College of Physicians 1. When prescribing testosterone, various forms can be considered, including injections, gels, patches, and pellets. For testosterone replacement therapy (TRT), injectable testosterone cypionate or enanthate is typically started at 50-100mg weekly or 100-200mg every two weeks intramuscularly. Topical options include testosterone gel applied daily to shoulders, upper arms, or abdomen at doses of 50-100mg. Transdermal patches are applied nightly at 2-6mg doses. Subcutaneous pellets provide 150-450mg lasting 3-6 months. Before prescribing, it is essential to confirm hypogonadism with two morning total testosterone measurements below 300 ng/dL along with symptoms, such as decreased energy, libido, muscle mass, and body hair, as well as hot flashes, gynecomastia, and infertility 1. Some key points to consider when prescribing testosterone replacement therapy include:

• Monitoring patients regularly with testosterone levels, hematocrit, PSA, and liver function tests to adjust dosing and maintain testosterone levels in the mid-normal range (400-700 ng/dL) 1.
• Testosterone therapy is contraindicated in men with breast or prostate cancer, untreated severe sleep apnea, severe heart failure, or hematocrit above 54% 1.
• The method of testosterone replacement should be individualized for each patient, considering factors such as convenience, cost, and potential side effects 1.
• Transdermal testosterone preparations, such as gels and patches, are often preferred due to their stability and convenience, but may have variable absorption and potential skin irritation 1.
• Injectable testosterone preparations, such as testosterone cypionate or enanthate, may be associated with a greater risk of cardiovascular events, but this risk may be unfounded and related to high-risk patient populations 1.

From the FDA Drug Label

To ensure proper dosing, the dose should be titrated based on the pre-dose morning serum testosterone concentration from a single blood draw at approximately 14 days and 28 days after starting treatment or following dose adjustment. Table 1 describes the dose adjustments required at each titration step. Table 1: Dose Adjustment Criteria Pre-Dose Morning Total Serum Testosterone Concentration Dose Titration Greater than 750 ng/dL Decrease daily dose by 20.25 mg (1 pump actuation or the equivalent of one 20.25 mg packet) Equal to or greater than 350 and equal to or less than 750 ng/dL No change: continue on current dose Less than 350 ng/dL Increase daily dose by 20.25 mg (1 pump actuation or the equivalent of one 20.25 mg packet) The prescribed daily dose of testosterone gel 1.62% should be applied to the right and left upper arms and shoulders as shown in the shaded areas in Figure 1. Testosterone gel 1.62% should be applied to clean, dry, intact skin of the upper arms and shoulders.

Prescribing Testosterone:

• The dose should be titrated based on the pre-dose morning serum testosterone concentration.
• Dose adjustments should be made according to Table 1.
• The prescribed daily dose should be applied to the right and left upper arms and shoulders.
• Application sites should be clean, dry, and intact.
• Administration instructions should be followed carefully to minimize the potential for secondary exposure to testosterone.
• Patients should be instructed to wash their hands with soap and water immediately after applying testosterone gel 1.62% 2. Key considerations:
• Monitor patients with BPH for worsening signs and symptoms.
• Evaluate patients for prostate cancer prior to initiating and during treatment with androgens.

From the Research

Diagnosis and Treatment of Male Hypogonadism

• Male hypogonadism is diagnosed based on clinical signs and symptoms, plus laboratory confirmation via the measurement of low morning testosterone levels on two different occasions 3.
• Serum luteinizing hormone and follicle-stimulating hormone levels distinguish between primary (hypergonadotropic) and secondary (hypogonadotropic) hypogonadism 3.
• Androgen replacement therapy in hypogonadal men has many potential benefits, including improved sexual function, an enhanced sense of well-being, increased lean body mass, decreased body fat, and increased bone density 3.

Testosterone Replacement Therapy

• Several products are currently marketed for the treatment of male hypogonadism, including weekly-to-biweekly injections of testosterone cypionate or testosterone enanthate, once-daily transdermal therapies, and intramuscular injection of testosterone undecanoate 3.
• To confirm an adequate replacement dosage, assessment of clinical responses and measurement of serum testosterone levels generally suffice 3.
• Testosterone supplementation therapy should be continued in individuals demonstrating an improvement in signs and symptoms, which may take 3 months to a year for maximum response 4.

Monitoring and Follow-up

• For men aged >50 years, measurement of hematocrit for detection of polycythemia and a digital rectal examination with a serum prostate-specific antigen level measurement for prostate cancer screening during the first few months of androgen therapy are recommended 3.
• A hematocrit should be obtained yearly or after changes in therapy, and annual prostate cancer screening can be offered to the patient after a discussion of its risks and benefits 3.
• Individuals treated with testosterone supplementation therapy require monitoring for adverse effects, and further studies are needed to determine the impact of testosterone supplementation therapy on cardiovascular health 4.

Special Considerations

• For young hypogonadal patients who may desire children in the future, alternatives such as clomiphene citrate and human chorionic gonadotropin have been shown to increase endogenous testosterone production and may be considered 5.
• The use of hormone testing for the diagnosis and evaluation of male hypogonadism and monitoring of testosterone therapy is not always performed in real-world clinical practice, and further investigation is needed into reasons for nonadherence to guidelines 6.