Diagnosis and Management of Primary Hypogonadism

Initial Biochemical Confirmation

The European Association of Urology recommends confirming the diagnosis of primary hypogonadism with two separate morning total testosterone measurements showing low levels (<300 ng/dL or <10.5 nmol/L) accompanied by elevated LH and FSH levels 1
Obtain two fasting morning testosterone measurements (between 8-10 AM) on separate occasions to confirm low testosterone, as diurnal variation is significant and single measurements are unreliable 3
Measure total testosterone first as the primary screening test 4
Add free testosterone by equilibrium dialysis if total testosterone is borderline (200-400 ng/dL) or if the patient is obese, as SHBG alterations can affect total testosterone interpretation 4
Measure SHBG levels to calculate free testosterone index (total testosterone/SHBG ratio <0.3 indicates hypogonadism) 3

Measure LH and FSH levels after confirming low testosterone to definitively classify the type of hypogonadism 4
Elevated LH and FSH with low testosterone confirms primary (hypergonadotropic) hypogonadism, indicating testicular failure 1
The European Urology guidelines state that medication review should include checking for drugs that interfere with testosterone production (glucocorticoids, opioids) 1

Evaluate for specific testicular pathology through history and physical examination, and check for drugs that interfere with testosterone production (glucocorticoids, opioids) 1

Screen for comorbid conditions that commonly coexist with hypogonadism, including thyroid function tests (TSH, free T4) to exclude thyroid disorders that can affect SHBG and testosterone metabolism 3
Perform bone density assessment (DXA scan of lumbar spine and femoral neck) if osteoporosis risk factors present or T-score evaluation needed 3
Corrected serum calcium and phosphate to assess bone metabolism 3
25-OH vitamin D levels if patient is housebound, has malabsorption, or is hypocalcemic 3

Screen for absolute contraindications before initiating treatment, including fertility assessment: Document if patient desires future fertility, as testosterone therapy suppresses spermatogenesis and is contraindicated in men seeking fertility 1
Metabolic evaluation: BMI, waist circumference, and screening for obesity, metabolic syndrome, and diabetes 1

Document specific hypogonadism symptoms to establish treatment indication, including sexual symptoms: reduced libido, erectile dysfunction, decreased frequency of sexual activity 1
Physical symptoms: decreased energy, reduced muscle mass, hot flashes, gynecomastia 1

Do not measure testosterone during acute illness, as levels are artificially suppressed and unreliable 1
Do not rely on screening questionnaires alone, as they lack specificity for systematic diagnosis 1
Do not initiate testosterone therapy without confirming elevated gonadotropins, as this would indicate secondary rather than primary hypogonadism and require different management 1