What is the optimal management strategy for a patient with a history of hypergonadism (elevated testosterone levels) due to non-prescription testosterone use, particularly regarding laboratory monitoring and dosage adjustments of testosterone replacement therapy (TRT)?

From the Guidelines

Testosterone therapy should be carefully managed with the goal of achieving a total testosterone level in the middle tertile of the normal reference range, and clinicians should adjust dosing accordingly. When initiating testosterone therapy, it is essential to begin with comprehensive baseline labs, including total and free testosterone, estradiol, complete blood count, comprehensive metabolic panel, lipid panel, and PSA (for men over 40) 1. For patients starting legitimate therapy, prescribe testosterone cypionate 100-200mg intramuscularly every 1-2 weeks or testosterone gel 50-100mg applied daily. Monitor labs at 3,6, and 12 months, then annually if stable.

Some key considerations for managing testosterone therapy include:

• Discontinuing all exogenous testosterone and allowing natural production to recover (which may take 3-6 months) for patients with a history of non-prescription use or elevated levels, then reassessing baseline levels 1
• Watching for polycythemia, elevated liver enzymes, lipid changes, and mood alterations during treatment
• Considering therapeutic phlebotomy and dose reduction if hematocrit exceeds 54%
• Including adjunctive therapies like human chorionic gonadotropin (hCG) 500-1500 IU 2-3 times weekly to maintain testicular function and fertility
• Using anastrozole 0.5-1mg weekly if estradiol levels rise excessively

Patient education about proper administration, realistic expectations, and potential risks, including cardiovascular effects, sleep apnea, and prostate issues, is essential for safe, effective treatment 1. The goal of testosterone therapy is the normalization of total testosterone levels combined with improvement in symptoms or signs, and treatment should be stopped if patients do not experience symptomatic relief after reaching the specified target testosterone levels or remain testosterone deficient in the setting of symptom/sign improvement 1.

From the FDA Drug Label

DOSAGE AND ADMINISTRATION Dosage and Administration for testosterone gel 1.62% differs from testosterone gel 1%. For dosage and administration of testosterone gel 1% refer to its full prescribing information. (2) Prior to initiating testosterone gel 1. 62%, confirm the diagnosis of hypogonadism by ensuring that serum testosterone has been measured in the morning on at least two separate days and that these concentrations are below the normal range (2). Starting dose of testosterone gel 1.62% is 40.5 mg of testosterone (2 pump actuations or a single 40.5 mg packet), applied topically once daily in the morning. (2. 1) Apply to clean, dry, intact skin of the shoulders and upper arms. Do not apply testosterone gel 1.62% to any other parts of the body including the abdomen, genitals, chest, armpits (axillae), or knees. (2.2,12.3) Dose adjustment: testosterone gel 1.62% can be dose adjusted between a minimum of 20.25 mg of testosterone (1 pump actuation or a single 20. 25 mg packet) and a maximum of 81 mg of testosterone (4 pump actuations or two 40.5 mg packets). 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. Additionally, serum testosterone concentration should be assessed periodically thereafter. (2. 1)

To effectively manage testosterone therapy, especially for patients with a history of elevated or high testosterone levels, the following steps should be taken:

• Confirm diagnosis: Ensure that serum testosterone has been measured in the morning on at least two separate days and that these concentrations are below the normal range before initiating testosterone gel 1.62% 2.
• Start with a recommended dose: The starting dose of testosterone gel 1.62% is 40.5 mg of testosterone, applied topically once daily in the morning 2.
• Monitor and adjust dose: 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 2.
• Assess serum testosterone concentration: Serum testosterone concentration should be assessed periodically thereafter to ensure that the patient's testosterone levels are within the normal range 2.
• Be cautious with non-prescription testosterone use: Patients with a history of elevated or high testosterone levels should be cautious when using non-prescription testosterone products, as they may increase the risk of adverse effects 2.
• Monitor for adverse effects: Patients should be monitored for signs and symptoms of adverse effects, such as virilization, benign prostatic hyperplasia, and venous thromboembolism 2.

Key points to consider:

• Dose adjustment: Testosterone gel 1.62% can be dose adjusted between a minimum of 20.25 mg of testosterone and a maximum of 81 mg of testosterone 2.
• Application site: Apply testosterone gel 1.62% to clean, dry, intact skin of the shoulders and upper arms, and avoid applying to other parts of the body 2.
• Patient education: Patients should be educated on the proper use of testosterone gel 1.62%, including how to apply the gel, how to wash their hands after application, and how to avoid skin-to-skin contact with others 2.

From the Research

Testosterone Therapy Management

To effectively manage testosterone therapy, several factors need to be considered, including diagnosis, treatment options, and monitoring of patients, especially those with a history of elevated or high testosterone levels.

• Diagnosis of hypogonadism should be made based on clinical signs and symptoms, plus laboratory confirmation via the measurement of low morning testosterone levels on two different occasions, as stated in 3.
• Treatment options for hypogonadism include weekly-to-biweekly injections of testosterone cypionate or testosterone enanthate, as well as once-daily transdermal therapies, such as patch and gel systems, and intramuscular injection of testosterone undecanoate, as mentioned in 3.
• For patients with a history of elevated or high testosterone levels, it is essential to monitor their response to treatment and adjust the dosage accordingly, as noted in 4, which observed changes in endocrine parameters in hypogonadal men over a 12-year period.

Monitoring and Follow-up

Regular monitoring and follow-up are crucial for patients undergoing testosterone therapy, particularly those with a history of elevated or high testosterone levels.

• Assessment of clinical responses and measurement of serum testosterone levels are generally sufficient to confirm an adequate replacement dosage, as stated in 3.
• For selected men, serial measurement of bone mineral density during androgen therapy might be helpful to confirm end-organ effects, as mentioned in 3.
• Patients aged >50 years should have their hematocrit measured 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, as recommended in 3.

Non-Prescription Testosterone Use

Concerns regarding non-prescription testosterone use highlight the need for careful evaluation and monitoring of patients.

• Authorities in the field have offered guidelines and recommendations regarding the diagnosis, evaluation, and management of hypogonadism, as discussed in 5.
• 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, as noted in 5.
• Individuals treated with testosterone supplementation therapy require monitoring for adverse effects, as stated in 5.

Treatment Options and Outcomes

Different treatment options are available for hypogonadal men, and their outcomes should be carefully evaluated.

• A comparison of outcomes for hypogonadal men treated with intramuscular testosterone cypionate versus subcutaneous testosterone enanthate found that both cohorts had significant increases in trough testosterone levels, but subcutaneous testosterone enanthate was associated with lower levels of post-therapy estradiol and hematocrit, as reported in 6.
• The Endocrine Society recommends making a diagnosis of hypogonadism only in men with symptoms and signs consistent with testosterone deficiency and unequivocally and consistently low serum testosterone concentrations, as stated in 7.
• The society also recommends measuring fasting morning total testosterone concentrations using an accurate and reliable assay as the initial diagnostic test and confirming the diagnosis by repeating the measurement of morning fasting total testosterone concentrations, as mentioned in 7.