What is the appropriate evaluation and treatment approach for a male patient with concerns about low testosterone levels?

Evaluation and Management of Low Testosterone in Males

Diagnose testosterone deficiency only when total testosterone is consistently below 300 ng/dL on two separate early morning measurements AND the patient has specific symptoms or signs of hypogonadism. 1

Diagnostic Criteria

Laboratory Confirmation

• Obtain two separate early morning (8-10 AM) total testosterone measurements using the same laboratory and methodology 1, 2
• Use 300 ng/dL as the diagnostic threshold for low testosterone 1
• Morning timing is critical due to diurnal variation in testosterone production 2

Required Clinical Features

The diagnosis requires BOTH low testosterone levels AND presence of symptoms/signs: 1

Symptoms to assess:

• Reduced energy, endurance, and physical performance 2
• Fatigue and diminished work performance 1, 2
• Decreased libido and erectile dysfunction 2
• Depression, reduced motivation, poor concentration, and impaired memory 2

Physical examination findings:

• Body habitus and virilization status (including hair patterns in androgen-dependent areas) 1, 2
• Testicular size, consistency, and presence of masses 2
• Gynecomastia 1, 2
• Body mass index and general morphology 2

Common Pitfall

Do not rely on symptom questionnaires alone to diagnose testosterone deficiency or monitor treatment response, as they are not currently validated for these purposes 1

Determining Etiology

Measure Luteinizing Hormone (LH)

• Check LH levels in all patients with confirmed low testosterone to distinguish primary from secondary hypogonadism 3, 2

If LH is Low or Low-Normal (Secondary Hypogonadism)

• Measure serum prolactin to screen for hyperprolactinemia and possible pituitary tumors 3, 2
• If prolactin is elevated, repeat measurement to confirm it is not spurious 3
• Persistently elevated prolactin warrants endocrinology referral 3
• Order pituitary MRI if testosterone is <150 ng/dL with low/normal LH, regardless of prolactin levels, as non-secreting adenomas may be present 3

If LH is Elevated (Primary Hypogonadism)

• This indicates testicular failure from conditions such as Klinefelter's syndrome, cryptorchidism, bilateral torsion, orchitis, orchiectomy, chemotherapy, or toxic damage 4

Additional Screening Indications

Consider measuring testosterone even without typical symptoms in patients with: 1

• Unexplained anemia
• Bone density loss
• Diabetes
• Chemotherapy or testicular radiation exposure
• HIV/AIDS
• Chronic narcotic use
• Male infertility
• Pituitary dysfunction
• Chronic corticosteroid use

Role of Scrotal Ultrasound

Scrotal ultrasound is NOT part of routine low testosterone evaluation. 5 Physical examination of the testes is sufficient in most cases. 5

Order scrotal ultrasound only when: 5

• Physical examination is inadequate (obesity, scrotal edema, patient discomfort limiting exam)
• Testicular mass is suspected (palpable nodule, asymmetric consistency, unexplained enlargement)
• Infertility evaluation with abnormal semen analysis requires objective testicular size measurement or varicocele detection

Treatment Approach

Indications for Testosterone Therapy

Initiate testosterone replacement only in symptomatic men with confirmed low testosterone levels to improve sexual function, sense of well-being, muscle mass and strength, and bone mineral density. 1

Absolute Contraindications

Do not start testosterone therapy in patients with: 4

• Breast or prostate cancer
• Palpable prostate nodule or induration
• PSA >4 ng/mL (or >3 ng/mL in high-risk men including African-Americans or those with first-degree relatives with prostate cancer) without urological evaluation
• Hematocrit >50%
• Untreated severe obstructive sleep apnea
• Severe lower urinary tract symptoms (IPSS >19)
• Uncontrolled or poorly controlled heart failure

Cardiovascular Considerations

Inform patients that long-term cardiovascular safety data are inconclusive, with some studies reporting increased risk of major adverse cardiovascular events (MACE) including non-fatal MI, stroke, and cardiovascular death. 4 The decision to use testosterone should weigh this uncertain risk against symptom burden.

Fertility Preservation

In patients desiring fertility, consider gonadotropin therapy or selective estrogen receptor modulators instead of testosterone, as exogenous testosterone suppresses spermatogenesis through FSH feedback inhibition. 2, 4

Dosing Strategy

• Target testosterone levels in the mid-normal range during treatment 2
• For testosterone gel 1.62%, start with 40.5 mg daily applied to shoulders and upper arms 4
• Titrate based on pre-dose morning testosterone at 14 and 28 days after initiation 4
• Adjust dose to maintain levels between 350-750 ng/dL 4

Monitoring Requirements

Monitor the following parameters regularly: 2, 4

• Hemoglobin/hematocrit (testosterone increases these values; polycythemia is the most significant cardiovascular-related adverse event)
• PSA in men over 40 years
• Serum testosterone levels to ensure therapeutic range
• Estradiol if gynecomastia or breast symptoms develop 2
• Lipid profile (may require dose adjustment or discontinuation) 4

Lifestyle Modifications

Weight loss through low-calorie diets can improve testosterone levels in obese patients with secondary hypogonadism, though increases are typically modest. 2 Regular physical activity shows similar benefits. 2 Consider combining lifestyle modifications with testosterone therapy for optimal results in symptomatic patients. 2

Critical Safety Warning

Patients using testosterone gel must avoid contact between application sites and children, as secondary exposure causes virilization in children. 4 Application sites must be washed before contact or covered with clothing. 4