What is the likely cause of fatigue in a 37-year-old male with normal total testosterone (923 ng/dL), free testosterone (33 pg/mL), and slightly elevated estradiol (48.9 pg/mL) levels?

From the Guidelines

Your fatigue is unlikely to be caused by low testosterone, given your normal total and free testosterone levels, and we should investigate other potential causes. Your total testosterone level of 923 ng/dL is within the normal range for adult men, as stated in the study by the American Urological Association 1, and your free testosterone level of 33 pg/mL is also adequate, although on the lower end of the normal range as defined by Wu et al. 1. Your estradiol level of 48.9 pg/mL is slightly elevated but probably not enough to cause significant symptoms. Given these results, the diagnosis of testosterone deficiency, as per the American Urological Association guidelines 1, cannot be made solely based on your hormone levels, as both total and free testosterone levels are within normal limits. The guidelines recommend that the diagnosis of low testosterone should be made only after two total testosterone measurements are taken on separate occasions with both conducted in an early morning fashion 1. However, since your hormone levels don't explain your fatigue, we should look for other potential causes, such as:

• Thyroid problems
• Anemia
• Sleep disorders
• Depression
• Stress
• Other medical conditions I recommend we do additional testing, including a complete blood count, thyroid function tests, and a comprehensive metabolic panel, as suggested by the NCCN clinical practice guidelines on cancer-related fatigue 1 and the American Society of Clinical Oncology clinical practice guideline adaptation on screening, assessment, and management of fatigue in adult survivors of cancer 1. In the meantime, try to maintain regular sleep patterns, engage in moderate physical activity, manage stress, and eat a balanced diet, as these lifestyle factors can significantly impact energy levels, as noted in the guidelines 1. Fatigue can have many causes beyond hormone imbalances, and finding the right explanation will help us develop an effective treatment plan for you.

From the Research

Laboratory Results

• The patient's total testosterone level is 923 ng/dL, which is within the normal reference range for adult males (264-916 ng/dL) 2.
• The free testosterone level is 33 pg/mL, also within the normal range, although on the lower end (46-81 pg/mL) 3.
• The estradiol level is 48.9 pg/mL, slightly elevated but may not be clinically significant without corresponding symptoms (normal range: 10-40 pg/mL) 4.

Diagnosis and Treatment

• The patient's fatigue is unlikely to be due to testosterone deficiency, as both total and free testosterone levels are within normal limits 4.
• The American Urological Association guidelines state that the diagnosis of testosterone deficiency requires both low testosterone levels and the presence of symptoms 4.
• Further evaluation for other causes of fatigue, such as:
  • Thyroid dysfunction: hyperthyroidism can cause fatigue, weight loss, and palpitations 5, 6.
  • Anemia: can be associated with thyroid dysfunction and may cause fatigue 5.
  • Sleep disorders: can contribute to fatigue.
  • Chronic diseases: may cause fatigue and should be ruled out.
• Assessing lifestyle factors such as sleep quality, stress, and physical activity may provide further insights into the patient's symptoms.

Next Steps

• Conduct further testing to rule out other causes of fatigue, such as thyroid function tests and complete blood count.
• Evaluate the patient's lifestyle factors and provide guidance on improving sleep quality, reducing stress, and increasing physical activity.
• Consider referring the patient to a specialist if a specific underlying condition is suspected.