Treatment for Low to Normal Testosterone Levels (Hypogonadism)
Testosterone replacement therapy should be considered when the morning free testosterone by equilibrium dialysis is frankly low on at least 2 separate assessments, and the hypogonadism workup has been completed to rule out an etiology unrelated to the primary condition. 1
Diagnosis of Hypogonadism
Initial Assessment
- Morning total testosterone concentration (between 8-10 AM) 1, 2
- Free testosterone level by equilibrium dialysis 1
- Sex hormone-binding globulin (SHBG) level 1, 2
- Repeat abnormal testosterone levels for confirmation 2, 3
- Measure luteinizing hormone (LH) and follicle-stimulating hormone (FSH) to distinguish primary from secondary hypogonadism 1, 2
Additional Testing When Indicated
- Serum prolactin and iron saturation 1
- Pituitary function testing 1
- MRI of sella turcica if secondary hypogonadism is suspected 1
- Estradiol levels if breast symptoms or gynecomastia are present 2
- Lipid panel, blood pressure, and fasting glucose/HbA1c 2
Treatment Algorithm
When to Initiate Treatment
- Confirmed low morning free testosterone on at least 2 separate assessments 1
- Presence of symptoms of hypogonadism (decreased energy, libido, muscle mass, body hair; hot flashes, gynecomastia, infertility) 1, 2
- Total testosterone <300 ng/dL (normal range: 300-800 ng/dL) 1, 4
- Free testosterone below normal range 1, 2
Contraindications to Testosterone Therapy
- Breast or prostate cancer 2, 4, 3
- Palpable prostate nodule or induration 3
- PSA >4 ng/mL or >3 ng/mL in high-risk men 3
- Hematocrit >50% 3
- Untreated severe obstructive sleep apnea 3
- Severe lower urinary tract symptoms 3
- Uncontrolled or poorly controlled heart failure 3
Treatment Options
Transdermal Testosterone Preparations (First-line)
Testosterone patches 1
Injectable Testosterone
- Advantages: Less frequent administration, lower cost 1
- Disadvantages: Fluctuating testosterone levels, injection discomfort 1
- Monitoring: Measure levels midway between injections, targeting 500-600 ng/dL 1
Implantable Testosterone Pellets
- Advantages: Long-term option with less frequent administration 1
- Disadvantages: Requires implantation procedure 1
Monitoring Protocol
- Test testosterone levels 2-3 months after treatment initiation or dose change 1
- Once stable levels achieved, monitor every 6-12 months 1
- For gels: Levels can be measured at any time (peak values 6-8 hours after application) 1
- For injections: Measure midway between injections 1
- Target testosterone level: 350-600 ng/dL (mid-normal range) 2
Special Considerations
Obesity and Hypogonadism
- Obesity can cause low total testosterone due to low SHBG 1
- Free testosterone may be normal despite low total testosterone 1
- Weight loss may improve testosterone levels 1
Secondary Exposure Risk with Gels
- Children should avoid contact with unwashed application sites 4
- Apply to areas covered by short-sleeve t-shirt 4
- Wash hands thoroughly after application 4
Benefits of Testosterone Replacement
- Improvements in energy, libido, muscle mass 1, 2
- Improved fasting glucose, insulin resistance, and lipid profile 1
- Enhanced bone mineral density 2
- Better quality of life 2, 5
Common Pitfalls to Avoid
- Relying solely on total testosterone without measuring free testosterone 1, 2
- Not confirming low testosterone with repeat morning measurements 2, 3
- Failing to distinguish between primary and secondary hypogonadism 1
- Not screening for contraindications before initiating therapy 3
- Inadequate monitoring of testosterone levels after treatment initiation 1
- Treating "age-related hypogonadism" without clear evidence of benefit 4
By following this structured approach to diagnosis and treatment of hypogonadism, clinicians can effectively manage patients with low to normal testosterone levels while optimizing outcomes related to morbidity, mortality, and quality of life.