What are the treatment options for males with hypogonadism (low testosterone)?

Treatment Options for Males with Hypogonadism (Low Testosterone)

Testosterone replacement therapy (TRT) is the primary treatment for men with confirmed hypogonadism, with treatment selection based on patient comorbidities, fertility concerns, and specific symptoms, while lifestyle modifications should be implemented concurrently.

Diagnosis and Evaluation

Before initiating treatment, proper diagnosis is essential:

• Confirm low testosterone with morning total testosterone levels below 350 ng/dL on at least two separate days 1
• Evaluate for symptoms consistent with hypogonadism:
  • Sexual symptoms: reduced frequency of intercourse/masturbation, delayed ejaculation 2
  • Physical symptoms: hot flushes, decreased energy, decreased physical strength 2
  • Cognitive symptoms: concentration difficulties, sleep disturbances 2
• Laboratory evaluation should include:
  • Morning total testosterone levels
  • Free testosterone
  • LH and FSH (to distinguish primary vs. secondary hypogonadism)
  • Complete blood count
  • PSA in men over 40 1

Treatment Algorithm

1. Lifestyle Modifications (First-Line)

• Weight loss for overweight/obese men
• Regular physical activity and exercise
• Adequate sleep
• Stress reduction techniques
• Healthy diet
• Moderate alcohol consumption
• Smoking cessation 1

2. Testosterone Replacement Therapy (TRT)

TRT is indicated for:

• Primary hypogonadism: testicular failure due to conditions like Klinefelter's syndrome, orchitis, orchiectomy 3
• Hypogonadotropic hypogonadism: pituitary or hypothalamic dysfunction 3

TRT should be initiated when:

• Total testosterone level is below 350 ng/dL with symptoms
• Levels between 231-346 ng/dL may warrant a 4-6 month trial if symptomatic
• Levels below 230 ng/dL usually benefit from treatment 1

TRT Formulations:

1. Injectable testosterone

   • Testosterone cypionate/enanthate: 50-100 mg weekly 1
   • Advantages: cost-effective, reliable absorption
   • Disadvantages: fluctuating levels, injection discomfort

2. Transdermal formulations

   • Testosterone gel 1.62%: 40.5 mg daily (2 pump actuations) applied to shoulders/upper arms 3
   • Advantages: steady hormone levels, ease of application
   • Disadvantages: risk of transfer to others, skin irritation

3. Testosterone pellets

   • Advantages: long-lasting (3-6 months), stable levels
   • Disadvantages: requires minor procedure for insertion 1

3. Alternative Therapies (When TRT is Contraindicated or Fertility is Desired)

• Clomiphene citrate or tamoxifen: For functional central hypogonadism, though off-label 4
• Gonadotropins (hCG, FSH): When fertility preservation is needed 2, 4
• Aromatase inhibitors: May be used for men with low testosterone and high estrogen levels 2

Monitoring and Follow-up

• Total testosterone levels: Target range 450-600 ng/dL 1
• Hematocrit: Discontinue if exceeds 54% 1
• PSA: Consider biopsy if >4.0 ng/mL or increases >1.0 ng/mL/year 1
• Digital rectal examination: Annually
• Bone mineral density: Baseline and follow-up in men with osteoporosis risk
• Cardiovascular risk assessment 1

Contraindications to TRT

• Active prostate or breast cancer
• Hematocrit >50%
• Severe untreated sleep apnea
• Uncontrolled heart failure
• Recent cardiovascular events (within 3-6 months) 1
• Men desiring fertility (testosterone suppresses spermatogenesis) 2

Benefits and Risks

Benefits:

• Improved sexual function (libido and erectile function)
• Increased energy levels and vitality
• Increased muscle mass and strength
• Improved bone mineral density
• Enhanced sense of well-being 1

Risks:

• Polycythemia (increased hematocrit)
• Potential cardiovascular risks (though evidence is inconclusive)
• Sleep apnea exacerbation
• Reduced fertility
• Skin reactions (more common with patches than gels)
• Potential for secondary exposure with gel formulations 1, 3, 5

Important Considerations

1. Fertility concerns: Testosterone monotherapy should not be prescribed for men interested in current or future fertility 2

2. Age-related hypogonadism: Safety and efficacy of TRT in men with "age-related hypogonadism" have not been established according to FDA labeling 3

3. Prostate health: Current evidence does not show that TRT increases prostate cancer risk, but monitoring is still recommended 1

4. Cardiovascular risk: The weight of evidence indicates TRT is not associated with increased cardiovascular risk in most men, but caution is advised in those with existing cardiovascular disease 2, 1

5. Treatment duration: Long-term treatment is typically required as symptoms usually return when treatment is discontinued 6