From the Guidelines
When deciding on testosterone replacement therapy, both total and free testosterone levels should be measured, with a morning total testosterone level assessed using an accurate and reliable assay, and free testosterone concentrations determined either directly or by calculations using total testosterone, sex hormone binding globulin, and albumin concentrations 1.
Key Considerations
- A diagnosis of testosterone deficiency typically requires a total testosterone level below the normal range, along with symptoms such as fatigue, decreased libido, or erectile dysfunction.
- Free testosterone is important, especially when total testosterone results are borderline or when conditions affecting sex hormone binding globulin (SHBG) exist.
- Testosterone replacement therapy may have benefits, including improved sexual function, well-being, muscle mass and strength, and bone density 1.
Measurement and Evaluation
- In men with symptoms or signs of low testosterone, a morning total testosterone level should be measured using an accurate and reliable assay 1.
- Further tests, such as luteinizing hormone and follicle-stimulating hormone levels, may be needed to further evaluate the individual.
Treatment Options
- Treatment should aim to achieve mid-normal range testosterone levels while monitoring for side effects.
- Regular follow-up testing is essential, checking testosterone levels, complete blood count, and PSA at 3-6 month intervals initially, then annually.
- Testosterone replacement affects the hypothalamic-pituitary-gonadal axis, so therapy typically continues indefinitely once started, as the body's natural production may not recover fully after prolonged treatment.
Recent Guidelines
- The Endocrine Society clinical practice guideline provides detailed recommendations for the evaluation and treatment of hypogonadism 1.
- The American College of Physicians has also issued guidelines on the efficacy and safety of testosterone treatment in men 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 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. Table 1 describes the dose adjustments required at each titration step. 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)
Testosterone levels for deciding on replacement are based on total serum testosterone concentrations.
- Total serum testosterone should be measured in the morning on at least two separate days.
- The diagnosis of hypogonadism should be confirmed by ensuring that serum testosterone concentrations are below the normal range.
- Dose adjustments should be made based on pre-dose morning total serum testosterone concentration.
- The target range for total serum testosterone concentration is between 350 ng/dL and 750 ng/dL.
- Free testosterone levels are not explicitly mentioned in the provided drug labels as a deciding factor for replacement therapy 2, 2, 2.
From the Research
Testosterone Levels and Replacement Therapy
- Total testosterone levels are used to diagnose hypogonadism, with a level of less than 300 to 350 ng/dL on two separate morning blood samples considered low 3
- Free testosterone levels are not explicitly mentioned in the provided studies as a deciding factor for replacement therapy
- The decision to start testosterone replacement therapy (TRT) is based on a combination of low testosterone levels and symptoms of hypogonadism, such as decreased libido, erectile dysfunction, and depressed mood 3, 4
Factors Influencing Testosterone Replacement Therapy
- The choice of testosterone formulation depends on factors such as cost, patient preference, and individual patient needs 3, 5
- Different formulations of TRT have varying effects on testosterone levels, estradiol, hematocrit, and prostate-specific antigen (PSA) 6
- The aim of TRT is to increase serum testosterone levels to a physiologic range, improving symptoms and signs of testosterone deficiency 4
Monitoring and Adjustments
- Patients receiving TRT require close monitoring to minimize risks and adjust treatment as needed 3, 4
- Clinicians must consider the unique characteristics of each patient and make individualized adjustments in the management of late-onset hypogonadism (LOH) 4
- Long-term TRT has been shown to reduce fatigue in men with hypogonadism, but its effects on cardiovascular risk and other endpoints are still being studied 7