From the Guidelines
Exogenous testosterone therapy can significantly impact Sex Hormone-Binding Globulin (SHBG) levels, and monitoring both total testosterone and SHBG is crucial to avoid potential side effects and ensure treatment effectiveness. When considering exogenous testosterone, it's essential to understand that SHBG binds to testosterone, making it unavailable for use by tissues, and only free (unbound) testosterone is biologically active 1.
Key Considerations for Testosterone Therapy
- Patients should be informed that testosterone therapy may result in improvements in erectile function, low sex drive, anemia, bone mineral density, lean body mass, and/or depressive symptoms 1.
- Prior to commencing testosterone therapy, baseline measurement of hemoglobin/hematocrit is necessary, and if the Hct exceeds 50%, clinicians should consider withholding testosterone therapy until the etiology is formally investigated 1.
- While on testosterone therapy, a Hct >54% warrants intervention, such as dose reduction or temporary discontinuation 1.
Monitoring and Dosage Adjustments
- Regular blood tests every 3-6 months are recommended to check testosterone (both total and free) and SHBG levels, allowing for dosage adjustments as needed.
- Lifestyle factors like maintaining healthy weight, limiting alcohol consumption, and avoiding anabolic steroids can help maintain appropriate SHBG levels during testosterone therapy.
- Typical dosages for testosterone replacement therapy (TRT) range from 50-200mg weekly for injectable testosterone cypionate or enanthate, or 50-100mg daily for testosterone gel preparations, but these may need to be adjusted based on individual responses and SHBG levels.
From the FDA Drug Label
Testosterone in plasma is 98 percent bound to a specific testosterone-estradiol binding globulin, and about 2 percent is free. Generally, the amount of this sex-hormone binding globulin in the plasma will determine the distribution of testosterone between free and bound forms, and the free testosterone concentration will determine its half-life
The sex-hormone binding globulin (SHBG) binds to testosterone in plasma.
- Binding of testosterone to SHBG: 98% of testosterone in plasma is bound to SHBG.
- Free testosterone: About 2% of testosterone is free. Exogenous testosterone administration may affect SHBG levels and the distribution of testosterone between free and bound forms, but the specific effects are not directly stated in the label 2.
From the Research
Exogenous Testosterone and SHBG
- Exogenous testosterone replacement therapy is a common treatment for men with low testosterone and symptomatic hypogonadism 3.
- However, exogenous testosterone replacement therapy can have negative effects on fertility due to its impact on the hypothalamic-pituitary-gonadal (HPG) axis 4.
- Sex hormone-binding globulin (SHBG) is a protein that binds to testosterone and other sex hormones, and its levels can affect the availability of testosterone in the body.
- Research has shown that lower SHBG levels are associated with lower mortality rates from all causes, cardiovascular disease, and cancer in men 5.
Effects of Exogenous Testosterone on SHBG
- Exogenous testosterone replacement therapy can affect SHBG levels, although the exact nature of this relationship is not fully understood 3, 6.
- Some studies suggest that exogenous testosterone replacement therapy can increase SHBG levels, while others have found no significant effect 6, 7.
- The relationship between exogenous testosterone and SHBG is complex and may depend on various factors, including the dose and duration of testosterone replacement therapy, as well as individual differences in hormone regulation.
Clinical Implications
- Clinicians should consider the potential effects of exogenous testosterone replacement therapy on SHBG levels and fertility when treating men with low testosterone 4, 7.
- Alternative treatments, such as selective estrogen receptor modulators (SERMs) and human chorionic gonadotropin (hCG) therapy, may be effective in increasing endogenous testosterone levels while preserving fertility 4.
- Further research is needed to fully understand the relationships between exogenous testosterone, SHBG, and mortality, as well as the optimal treatment strategies for men with low testosterone and symptomatic hypogonadism 3, 5.