Workup for Primary Hypogonadism
In primary hypogonadism, confirm the diagnosis with two separate morning (8-10 AM) total testosterone measurements showing low levels (<300 ng/dL or <10.5 nmol/L) accompanied by elevated LH and FSH levels, then evaluate for underlying testicular causes and assess for contraindications to testosterone therapy. 1, 2
Initial Biochemical Confirmation
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. 1
- Measure total testosterone first as the primary screening test. 1
- 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. 1, 2
- Measure SHBG levels to calculate free testosterone index (total testosterone/SHBG ratio <0.3 indicates hypogonadism). 1
Distinguish Primary from Secondary Hypogonadism
Measure LH and FSH levels after confirming low testosterone to definitively classify the type of hypogonadism. 1, 2, 3
- Elevated LH and FSH with low testosterone confirms primary (hypergonadotropic) hypogonadism, indicating testicular failure. 1, 2
- Low or inappropriately normal LH/FSH with low testosterone indicates secondary hypogonadism, not primary. 2
Identify Underlying Causes of Primary Hypogonadism
Evaluate for specific testicular pathology through history and physical examination:
- Congenital causes: cryptorchidism, vanishing testis syndrome, Klinefelter syndrome. 4
- Acquired causes: bilateral testicular torsion, orchitis, orchidectomy, chemotherapy, radiation exposure. 4
- Medication review: check for drugs that interfere with testosterone production (glucocorticoids, opioids). 1
Additional Laboratory Assessment
Screen for comorbid conditions that commonly coexist with hypogonadism:
- Thyroid function tests (TSH, free T4) to exclude thyroid disorders that can affect SHBG and testosterone metabolism. 1, 5
- Bone density assessment (DXA scan of lumbar spine and femoral neck) if osteoporosis risk factors present or T-score evaluation needed. 1
- Corrected serum calcium and phosphate to assess bone metabolism. 1
- 25-OH vitamin D levels if patient is housebound, has malabsorption, or is hypocalcemic. 1
- Hemoglobin and hematocrit as baseline before considering testosterone therapy. 3, 6
Assess for Testosterone Therapy Contraindications
Screen for absolute contraindications before initiating treatment:
- PSA and digital rectal examination in men >50 years to screen for prostate cancer. 3, 6
- Fertility assessment: Document if patient desires future fertility, as testosterone therapy suppresses spermatogenesis and is contraindicated in men seeking fertility. 1, 2
- Metabolic evaluation: BMI, waist circumference, and screening for obesity, metabolic syndrome, and diabetes. 1
Clinical Symptom Documentation
Document specific hypogonadism symptoms to establish treatment indication:
- Sexual symptoms: reduced libido, erectile dysfunction, decreased frequency of sexual activity. 1, 2
- Physical symptoms: decreased energy, reduced muscle mass, hot flashes, gynecomastia. 1, 2
- Cognitive symptoms: concentration difficulties, memory problems, sleep disturbances. 2
Key Pitfalls to Avoid
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. 2
Remember that primary hypogonadism patients can only receive testosterone therapy and cannot achieve fertility restoration, unlike secondary hypogonadism where gonadotropin therapy can preserve fertility. 1, 2