What is the workup and treatment for hypogonadism (low sex hormone production)?

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Workup and Treatment for Hypogonadism

The cornerstone of diagnosing hypogonadism requires the presence of specific signs and symptoms combined with laboratory confirmation of decreased morning total testosterone levels measured on at least two separate occasions, with levels below 300 ng/dL confirming the diagnosis. 1, 2

Diagnostic Workup

Clinical Assessment

  • Sexual symptoms: Reduced libido, erectile dysfunction, decreased spontaneous/morning erections 2
  • Physical symptoms: Decreased energy, decreased physical strength/activity, fatigue 2
  • Psychological symptoms: Low mood, decreased motivation, concentration difficulties 2

Laboratory Testing

  1. Initial hormone panel:

    • Morning total testosterone (measure at least twice, preferably before 10 AM)
    • Luteinizing hormone (LH)
    • Follicle-stimulating hormone (FSH) 2

  2. Additional baseline measurements:

    • Hemoglobin/hematocrit
    • Prostate-specific antigen (PSA) in men over 40
    • Assessment of cardiovascular risk factors 2

Classification of Hypogonadism

  • Primary hypogonadism: High LH/FSH with low testosterone (testicular failure)
  • Secondary hypogonadism: Low/normal LH/FSH with low testosterone (pituitary/hypothalamic dysfunction) 1, 3

Evaluation for Underlying Causes

  1. Medication review: Check for drugs that can cause hypogonadism:

    • Opioids
    • Estrogens
    • Testosterone/androgenic anabolic steroids
    • Glucocorticoids
    • GnRH agonists/antagonists
    • Verapamil
    • Spironolactone 2

  2. Metabolic assessment:

    • BMI and waist circumference
    • Screening for obesity, metabolic syndrome, diabetes 1

  3. Rule out acute illness: Avoid testosterone testing during acute illness 1

Treatment Approaches

Primary Hypogonadism

Testosterone Replacement Therapy (TRT):

  • First-line options:

    • Intramuscular testosterone (recommended as initial treatment due to effectiveness and lower cost) 2
    • Transdermal preparations (gels, patches) provide more stable day-to-day levels 2

  • Target testosterone levels: 450-600 ng/dL (mid-normal range) 2

  • Dose adjustment guide:

    Pre-Dose Morning Testosterone Dose Adjustment
    >750 ng/dL Decrease daily dose by 20-25%
    350-750 ng/dL No change
    <350 ng/dL Increase daily dose by 20-25%

Secondary Hypogonadism with Fertility Concerns

  1. Clomiphene citrate: Commonly prescribed off-label to preserve fertility 2

  2. Gonadotropin therapy:

    • Start with human chorionic gonadotropin (hCG)
    • Add FSH if needed after 6 months if sperm production inadequate 2, 4
    • Effective in promoting spermatogenesis in approximately 80% of patients 4

Lifestyle Interventions

  • Weight loss through low-calorie diets can reverse obesity-associated secondary hypogonadism 1, 2
  • Combining lifestyle changes with TRT may yield better outcomes in symptomatic patients 2

Monitoring and Safety

Follow-up Testing

  • Testosterone levels: After starting treatment and every 6-12 months 2
  • Hemoglobin/hematocrit: Discontinue treatment if Hct >54% 2
  • PSA: Monitor according to guidelines; consider discontinuation if significant increase 2, 5
  • Estradiol: Monitor for gynecomastia 2

Contraindications for TRT

  • Absolute contraindications:

    • Prostate cancer
    • Breast cancer
    • Desire for near-term fertility
    • Severe sleep apnea
    • Uncontrolled heart failure
    • Recent cardiovascular events 2

  • Relative contraindications:

    • History of hepatocellular carcinoma
    • Thrombosis
    • Other cardiovascular risk factors 2

Potential Side Effects

  • Erythrocytosis (dose-dependent: 2.8-17.9%)
  • Suppression of spermatogenesis
  • Peripheral edema
  • Emotional lability
  • Increased PSA (11.1% in clinical trials)
  • Gynecomastia 2, 5

Special Considerations

  • TRT should not be prescribed to men interested in current or future fertility 2
  • Evaluate reproductive health if fertility is desired 2
  • Consider testicular exam and serum FSH measurement in fertility assessment 2

Treatment Outcomes

  • Improved sexual function and libido
  • Small improvements in quality of life
  • Potential improvements in bone mineral density and lean body mass
  • Possible improvements in depressive symptoms 2

References

1
Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

2
Guideline

Testosterone Replacement Therapy

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

3
Research

Male hypogonadism.

Lancet (London, England), 2014

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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