Treatment for Low Free Testosterone and Total Testosterone Levels
Testosterone replacement therapy is indicated for patients with confirmed low testosterone levels (total testosterone <300 ng/dL on two separate morning measurements) combined with symptoms and/or signs of testosterone deficiency. 1
Diagnostic Confirmation
- The diagnosis of testosterone deficiency requires both consistently low testosterone measurements (<300 ng/dL) on at least two separate morning tests AND the presence of symptoms/signs 1
- Free testosterone measurement is essential when evaluating low total testosterone in patients with obesity or suspected binding protein abnormalities 1, 2
- Clinical symptoms that warrant evaluation include reduced energy, reduced endurance, fatigue, depression, reduced motivation, poor concentration, infertility, reduced sex drive, and changes in erectile function 1
Treatment Options
First-Line Treatment: Transdermal Testosterone Preparations
- Transdermal testosterone preparations (gels, patches) are generally preferred as first-line options due to their steady-state pharmacokinetics 2, 3
- These formulations avoid the fluctuations in testosterone levels seen with injectable formulations 3
Alternative Options: Injectable Testosterone
- Testosterone cypionate or enanthate can be administered intramuscularly at intervals of two to four weeks 4, 5, 6
- Injectable testosterone has a half-life of approximately eight days when administered intramuscularly 6
- These formulations are absorbed slowly from the lipid phase, allowing for less frequent dosing 4, 5
Monitoring Therapy
- After initiating treatment, monitor testosterone levels at 2-3 months and after any dose change 2
- For patients receiving testosterone injections, levels should be measured midway between injections 2
- Once stable levels are confirmed, monitoring every 6-12 months is typically sufficient 2
- Target normal free testosterone levels rather than just total testosterone, especially in patients with abnormal SHBG levels 2, 7
Special Considerations
- Before initiating treatment, measure luteinizing hormone (LH) levels to determine if hypogonadism is primary or secondary 2
- Consider measuring serum prolactin to rule out hyperprolactinemia as a cause of secondary hypogonadism 2
- In patients with obesity, low total testosterone may be due to low sex hormone-binding globulin, requiring free testosterone measurement to confirm true testosterone deficiency 1
- Increased aromatization of testosterone to estradiol in adipose tissue can lead to estradiol-mediated negative feedback suppressing pituitary LH secretion in obese men 1
Common Pitfalls to Avoid
- Relying solely on total testosterone without measuring free testosterone in patients with suspected binding protein abnormalities 1, 7
- Initiating treatment based on a single testosterone measurement rather than confirming with two separate morning tests 1
- Treating patients with testosterone without confirming the presence of both low testosterone levels and clinical symptoms 1
- Failing to monitor testosterone levels after initiating therapy - nearly half of men on testosterone therapy do not have their levels checked after starting treatment 1