From the Guidelines
The next step if total testosterone level is normal but free testosterone is low is to consider lifestyle modifications and evaluate for underlying conditions that can affect free testosterone levels, as low free testosterone can be associated with various health issues, including decreased energy, libido, and muscle mass, as well as increased risk of cardiovascular events 1. Key steps may include:
- Assessing and potentially reducing Sex Hormone Binding Globulin (SHBG) levels, which can bind excess testosterone
- Considering lifestyle modifications, such as:
- Improving sleep quality (aim for 7-9 hours per night)
- Reducing stress through relaxation techniques or counseling
- Optimizing diet by increasing healthy fats and reducing sugar intake
- Exercising regularly, focusing on resistance training
- Evaluating for underlying conditions like liver disease, thyroid disorders, or obesity that can affect free testosterone levels
- Discussing medication options with a doctor, such as testosterone replacement therapy, if lifestyle modifications are not effective in improving free testosterone levels, as testosterone replacement has been associated with favorable results, including weight loss, improvements in fasting plasma glucose, insulin resistance, and lipid profiles 1. It is essential to consult an endocrinologist or urologist for a thorough evaluation and to determine the best course of treatment, as the management of low free testosterone requires a comprehensive approach that takes into account the individual's overall health and medical history 1.
From the Research
Next Steps for Normal Total Testosterone but Low Free Testosterone
- If a patient has a normal total testosterone level but low free testosterone, further evaluation and assessment of symptoms is necessary 2.
- Measurement of free or bioavailable testosterone with a reliable assay can help clarify the clinical picture in equivocal cases 3.
- The diagnosis of hypogonadism includes both clinical history and examination as well as biochemical assessment of serum testosterone levels 2.
- A trial period of testosterone treatment may be required for patients with total testosterone levels in the grey zone (between 8 and 12 nmol/l) or with low free testosterone 2.
- Total testosterone measurement has low specificity for the biochemical diagnosis of hypogonadism, except when levels are less than 150 ng/dl 4.
- Testosterone replacement therapy (TRT) may be considered for patients with hypogonadism, but management discussions should be individualized to address patient needs and goals 5.
Considerations for Testosterone Replacement Therapy
- Patients should meet criteria for hypogonadism, which is defined as a low testosterone level and signs or symptoms of hypogonadism 5.
- Counseling before therapy should include shared decision-making regarding risks, benefits, and expectations 5.
- Numerous testosterone formulations are available, ranging from topical gels to intramuscular injections, and the choice of formulation depends on factors such as cost and patient preference 5.
Importance of Free Testosterone Measurement
- Measurement of free testosterone is important in the diagnosis of many diseases, most importantly disorders of androgen deficiency in men (i.e., hypogonadism) and androgen excess in women (i.e., polycystic ovary syndrome and hirsutism) 6.
- Free testosterone is believed to be the metabolically active fraction of testosterone, and its measurement can help identify patients with low testosterone levels despite normal total testosterone levels 6.