How is hypogonadism diagnosed?

Diagnosis of Hypogonadism

The diagnosis of hypogonadism requires both persistent specific symptoms and confirmed testosterone deficiency through biochemical testing, with morning total testosterone measurements repeated on at least two separate days. 1

Clinical Assessment

Symptoms and Signs

• Decreased libido and vitality are common symptoms of hypogonadism 2
• Erectile dysfunction may indicate hypogonadism 2
• Other symptoms include reduced energy, reduced endurance, fatigue, depression, poor concentration, and infertility 3
• Physical signs may include decreased body hair, gynecomastia, and reduced muscle mass 4

History Taking

• Evaluate for pituitary disorders, surgical history, comorbidities, and medications affecting the hypothalamic-pituitary-gonadal axis 1
• Check for drugs and substances that can interfere with testosterone production/action 1
• Assess for concomitant metabolic diseases: obesity, metabolic syndrome, diabetes 1
• Determine fertility concerns, as this impacts treatment options 1
• Avoid testosterone testing during acute illness as results may be transiently suppressed 1, 5

Physical Examination

• Measure body mass index (BMI) and waist circumference 1
• Evaluate testicular size and consistency 6
• Check for signs of other endocrine disorders 4

Laboratory Diagnosis

Initial Testing

• Morning serum total testosterone measurement (between 8 AM and 10 AM) is essential 2, 7
• Repeat measurements on at least two separate days to confirm low levels 2, 7, 5
• Total testosterone levels <8 nmol/L (approximately 230 ng/dL) highly support diagnosis of hypogonadism 4
• Levels >12 nmol/L (approximately 350 ng/dL) are likely normal 4
• For values between 8-12 nmol/L, further evaluation is needed 4

Additional Testing

• Measure free testosterone by equilibrium dialysis or calculate free testosterone, especially in men with obesity or conditions that alter sex hormone-binding globulin 2, 5
• Measure luteinizing hormone (LH) and follicle-stimulating hormone (FSH) to distinguish primary from secondary hypogonadism 2, 6
• Primary hypogonadism: high LH/FSH with low testosterone 6
• Secondary hypogonadism: low or inappropriately normal LH/FSH with low testosterone 6, 8
• Consider measuring serum prolactin in patients with low testosterone combined with low or low/normal LH levels 3

Classification of Hypogonadism

Primary Hypogonadism (Hypergonadotropic)

• Caused by testicular dysfunction 1
• Characterized by high LH/FSH levels 6
• Common causes include Klinefelter syndrome, cryptorchidism, orchitis, trauma, radiation, chemotherapy 1

Secondary Hypogonadism (Hypogonadotropic)

• Results from impairment of the hypothalamic-pituitary-gonadal axis 1
• Characterized by low or inappropriately normal LH/FSH levels 8
• Common causes include pituitary tumors, hemochromatosis, medications, and functional disorders (obesity, stress, excessive exercise) 1, 8

Functional Hypogonadism

• Diagnosed based on absence of organic alterations in the HPG axis 1
• Often associated with obesity, metabolic syndrome, chronic illness, medications 1
• Treatment should first address underlying conditions 1

Common Pitfalls to Avoid

• Diagnosing based on symptoms alone without laboratory confirmation 3
• Failing to distinguish between primary and secondary hypogonadism 3
• Not considering other causes of similar symptoms before attributing them to testosterone deficiency 3
• Testing testosterone levels during acute illness 1
• Not repeating testosterone measurements to confirm diagnosis 5
• Overlooking conditions that alter sex hormone-binding globulin when interpreting total testosterone levels 2, 5

Special Considerations

• In men with obesity, free testosterone is a better indicator than total testosterone 2
• The grey zone between 8-12 nmol/L total testosterone requires assessment of free testosterone and clinical symptoms 4
• Late-onset hypogonadism (LOH) often occurs without identifiable causes and increases with age 1
• Screening questionnaires have clinical value but lack specificity for systematic screening 1

By following this diagnostic approach, clinicians can accurately identify hypogonadism, determine its etiology, and guide appropriate treatment decisions that will ultimately improve patient morbidity, mortality, and quality of life.