From the Guidelines
When total testosterone is low but free testosterone is normal, treatment is usually not necessary, as the biologically active form of testosterone, free testosterone, is within normal ranges 1. This situation occurs because most testosterone in the blood is bound to proteins (sex hormone-binding globulin and albumin), while only 1-2% circulates as free testosterone, which is the biologically active form. Free testosterone is what actually enters cells and produces testosterone's effects in the body, so if this level is normal, you're likely experiencing appropriate hormonal function despite the low total value.
The discrepancy often occurs due to variations in binding protein levels, which can be affected by factors like liver disease, thyroid disorders, obesity, or aging. If you're not experiencing symptoms like fatigue, decreased libido, or muscle loss, monitoring without intervention is typically recommended, as suggested by the American College of Physicians in their clinical guideline for testosterone treatment in adult men with age-related low testosterone 1.
However, if you have symptoms despite normal free testosterone, your doctor might consider a trial of testosterone replacement therapy starting with a moderate dose while monitoring both symptoms and blood levels. Before considering treatment, it's essential to have a complete hormonal evaluation, including luteinizing hormone, estradiol, and prolactin, to identify any underlying causes, as emphasized in the evidence report for a clinical practice guideline by the American College of Physicians 1.
Key considerations in managing low total testosterone with normal free testosterone include:
- Monitoring symptoms and blood levels without immediate intervention if asymptomatic
- Considering testosterone replacement therapy for symptomatic patients
- Conducting a complete hormonal evaluation to identify underlying causes
- Following clinical guidelines that suggest not initiating testosterone treatment for nonspecific symptoms like decreased energy or mobility without established hypogonadism 1.
From the Research
Low Total Testosterone and Normal Free Testosterone
- Men with low total testosterone and normal free testosterone levels may not exhibit symptoms of hypogonadism, as free testosterone is a better indicator of androgen deficiency 2.
- A study found that men with normal total testosterone and low free testosterone were older and in poorer health, with higher SHBG and LH levels, and reported more sexual and physical symptoms 2.
- In contrast, men with low total testosterone and normal free testosterone were younger and more obese, with lower SHBG levels and normal LH levels, and lacked features of androgen deficiency 2.
- The assessment of free testosterone levels is important in diagnosing functional hypogonadism, especially in men with sexual symptoms, as it allows for a more accurate diagnosis than total testosterone levels alone 3.
Clinical Implications
- Testosterone replacement therapy (TRT) may be beneficial for men with hypogonadism, including those with low total testosterone and normal free testosterone, as it can improve libido, sexual function, bone density, muscle mass, and mood 4, 5, 6.
- However, the decision to initiate TRT should be based on a comprehensive evaluation of the patient's symptoms, medical history, and laboratory results, including free testosterone levels 3, 2.
- Further research is needed to fully understand the effects of testosterone on men's health and to develop more effective treatment strategies for hypogonadism 5, 6.