What is the initial workup and treatment for a male patient with suspected hypogonadism (low sex hormone production)?

Male Hypogonadism Workup

The workup for suspected male hypogonadism requires morning total testosterone measurement (8-10 AM) on two separate occasions combined with assessment of specific symptoms, followed by LH/FSH levels to distinguish primary from secondary hypogonadism. 1, 2

Initial Clinical Assessment

Symptom Evaluation

The diagnosis requires both biochemical confirmation and persistent specific symptoms 1:

Sexual symptoms (most specific):

• Reduced frequency of sexual intercourse 1
• Decreased libido 2
• Erectile dysfunction 2
• Reduced frequency of masturbation 1
• Delayed ejaculation 1

Physical symptoms:

• Hot flushes 1
• Decreased energy and physical strength 1
• Reduced physical activity 1

Cognitive/psychological symptoms (least specific):

• Concentration or memory difficulties 1
• Sleep disturbances 1

Critical History Elements

• Medications affecting testosterone: Opiates, glucocorticoids, GnRH agonists/antagonists, anabolic steroids, estrogens, progestogens 1
• Comorbidities: Type 2 diabetes, metabolic syndrome, obesity, chronic organ failure, HIV infection 1
• Fertility concerns: This fundamentally changes treatment approach 1, 2
• Surgical history and pituitary disorders 1
• Avoid testing during acute illness 1

Physical Examination

• Body mass index (BMI) and waist circumference 1
• Testicular volume assessment 1
• Signs of virilization 1

Laboratory Workup Algorithm

Step 1: Initial Testosterone Testing

• Morning total testosterone (8-10 AM) on two separate occasions due to assay variability 2, 3
• Free testosterone by equilibrium dialysis (especially in obesity, as SHBG is decreased) 2
• Sex hormone-binding globulin (SHBG) level 2

SHBG is decreased by: obesity, hypothyroidism, insulin resistance, metabolic syndrome, type 2 diabetes, glucocorticoids, growth hormone, anabolic steroids 1

SHBG is increased by: aging, hyperthyroidism, hepatic disease, anticonvulsants, estrogens, thyroid hormone 1

Step 2: Confirm Hypogonadism

• Total testosterone <275 ng/dL (9.54 nmol/L) confirms hypogonadism 2
• Total testosterone <8 nmol/L profoundly suggests hypogonadism 4
• Total testosterone 8-12 nmol/L represents a "grey zone" requiring symptom correlation 4

Step 3: Distinguish Primary vs Secondary Hypogonadism

If testosterone is confirmed low, measure:

• Luteinizing hormone (LH) 2, 3
• Follicle-stimulating hormone (FSH) 2, 3
• Prolactin 5

Interpretation:

• Primary (hypergonadotropic) hypogonadism: Low testosterone + elevated LH/FSH (testicular dysfunction) 1, 3
• Secondary (hypogonadotropic) hypogonadism: Low testosterone + low or inappropriately normal LH/FSH (hypothalamic-pituitary dysfunction) 1, 6
• Functional hypogonadism: Normal testosterone with elevated LH, or low testosterone without organic HPG axis pathology, often due to obesity/metabolic disease 1

Additional Testing Based on Clinical Context

For Secondary Hypogonadism

• Pituitary imaging (MRI) if pituitary pathology suspected 5
• Other pituitary hormone testing if combined pituitary hormone deficiency suspected 1

For All Patients Before Treatment

• Hematocrit (baseline for monitoring erythrocytosis risk) 2, 3
• PSA and digital rectal exam in men >40 years 2, 3
• Fasting glucose and lipid panel (metabolic assessment) 2

Optional/Specialized Testing

• Semen analysis if fertility concerns 5
• Bone densitometry in long-standing hypogonadism 3, 5
• Testicular ultrasonography for structural abnormalities 5
• Genetic studies for congenital causes (Klinefelter syndrome, etc.) 5

Common Causes by Category

Primary Hypogonadism Causes

• Klinefelter syndrome 1
• Chemotherapy/radiation 1
• Testicular trauma 1
• Orchitis (mumps) 1
• Cryptorchidism 1

Secondary Hypogonadism Causes

• Drug-induced: Opiates, glucocorticoids, anabolic steroids 1
• Pituitary tumors (micro/macroadenomas) 1
• Idiopathic hypogonadotropic hypogonadism (including Kallmann syndrome) 1
• Hyperprolactinemia 1
• Chronic systemic diseases: Type 2 diabetes, metabolic syndrome, obesity, HIV 1

Functional Hypogonadism Triggers

• Obesity (most common) 1
• Type 2 diabetes/metabolic syndrome 1
• Chronic inflammatory conditions 1
• Aging 1

Critical Pitfalls to Avoid

• Do not test testosterone during acute illness as levels are transiently suppressed 1
• Do not rely on single testosterone measurement due to pulsatile secretion and assay variability 2, 3
• Do not use screening questionnaires alone as they lack specificity 1
• Do not miss fertility assessment before initiating testosterone therapy, as it suppresses spermatogenesis 1, 2, 7
• Do not overlook reversible causes (medications, obesity) that should be addressed first 1