From the Guidelines
Treatment is typically recommended for individuals with normal total testosterone but low free testosterone levels, as free testosterone represents the biologically active form of the hormone. This recommendation is based on the most recent and highest quality study available, which suggests that testosterone replacement therapy (TRT) can improve symptoms and quality of life in these individuals 1.
Key Considerations
- Before starting treatment, it's essential to identify potential causes of low free testosterone, such as elevated sex hormone-binding globulin (SHBG) levels, which can be due to liver disease, hyperthyroidism, or certain medications.
- Treatment aims to improve symptoms like fatigue, decreased libido, erectile dysfunction, and reduced muscle mass.
- Regular monitoring of testosterone levels, complete blood count, prostate-specific antigen, and liver function is necessary during therapy.
- The goal is to achieve testosterone levels in the mid-normal range while alleviating symptoms and minimizing side effects such as polycythemia, acne, or prostate issues.
Treatment Options
- Testosterone replacement therapy (TRT) can be administered through various methods, including:
- Intramuscular injections (such as testosterone cypionate 50-100mg weekly or testosterone enanthate 100-200mg every 2 weeks)
- Transdermal gels (AndroGel or Testim 50-100mg applied daily)
- Patches (Androderm 2-6mg applied nightly)
- Pellets (implanted subcutaneously every 3-6 months)
- The method of testosterone replacement should be individualized for each patient, taking into account factors such as convenience, cost, and potential side effects 1.
Monitoring and Adjustment
- Testosterone levels should be tested 2 to 3 months after treatment initiation, and/or after any dose change.
- Once stable levels are confirmed on a given dose, monitoring every 6 to 12 months is typically sufficient.
- The goal of testosterone therapy is to achieve a total testosterone level in the middle tertile of the normal reference range, which is typically considered to be 450-600 ng/dL 1.
From the Research
Total Testosterone and Free Testosterone Levels
- Total testosterone levels are often used to diagnose androgen deficiency, but free testosterone levels can also be an important indicator of hypogonadal symptoms 2.
- Men with normal total testosterone levels but low free testosterone levels may still experience hypogonadal signs and symptoms, such as sexual and physical symptoms, and lower hemoglobin and bone ultrasound parameters 2.
- Low free testosterone levels, even in the presence of normal total testosterone levels, are associated with androgen deficiency-related symptoms 2.
Treatment Options for Hypogonadism
- Testosterone replacement therapy (TRT) can restore normal serum testosterone concentrations and relieve symptoms in most hypogonadal men, but it may suppress spermatogenesis 3, 4, 5.
- Human chorionic gonadotropin (hCG) and clomiphene citrate (CC) are alternative treatments that can increase endogenous testosterone production and may be used to preserve fertility in hypogonadal men 4, 6.
- A combination of hCG and CC may be more effective in restoring testosterone levels and improving symptoms than either treatment alone 6.
Fertility Preservation
- TRT can induce reversible suppression of spermatogenesis, but fertility may be preserved with the use of hCG, CC, or other treatments that stimulate endogenous testosterone production 3, 5.
- Men with hypogonadism who desire to preserve their fertility may be treated with hCG, CC, or a combination of both, which can restore testosterone levels and improve symptoms without suppressing spermatogenesis 6.