What are the guidelines for testing and treating low testosterone levels in patients?

Testosterone Testing and Treatment Guidelines

Diagnostic Criteria

Testosterone deficiency requires both consistently low testosterone levels (<300 ng/dL on two separate morning measurements) AND the presence of clinical symptoms/signs of hypogonadism. 1, 2

Laboratory Testing Requirements

• Measure total testosterone on two separate mornings between 8-10 AM using the same laboratory and methodology to confirm diagnosis 1, 2, 3
• The diagnostic threshold is <300 ng/dL on both measurements 1, 2
• Morning timing is critical due to diurnal variation in testosterone production, even in older men 1, 2, 4
• If total testosterone is near the lower limit of normal (borderline), measure free or bioavailable testosterone using validated assays (equilibrium dialysis or accurate formula) 1, 5

Clinical Symptoms to Assess

Patients must have symptoms consistent with testosterone deficiency, including: 1, 2

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

Physical Examination Findings

Conduct a targeted examination evaluating: 1, 2

• Body habitus and BMI/waist circumference
• Virilization status (body hair patterns in androgen-dependent areas)
• Gynecomastia
• Testicular size, consistency, presence, and masses
• Varicocele presence
• Prostate size and morphology

High-Risk Populations Requiring Testing

Measure testosterone in all patients with the following conditions, even without symptoms: 1

• Unexplained anemia
• Bone density loss
• Diabetes
• History of chemotherapy or testicular radiation
• HIV/AIDS
• Chronic narcotic use
• Chronic corticosteroid use
• Pituitary disorders
• Infertility

Adjunctive Laboratory Testing

Essential Additional Tests

• Measure serum LH in all patients with confirmed low testosterone to establish etiology (primary vs. secondary hypogonadism) 1, 6
• Measure serum prolactin if testosterone is low AND LH is low or low-normal to screen for hyperprolactinemia 1, 6
• If prolactin is elevated, repeat measurement to confirm it is not spurious 1
• Persistently elevated prolactin requires endocrinology referral for evaluation of pituitary tumors 1
• If total testosterone <150 ng/dL with low/normal LH, obtain pituitary MRI regardless of prolactin levels to evaluate for non-secreting adenomas 1, 6
• Measure serum estradiol if breast symptoms or gynecomastia are present before starting therapy 1, 6

Treatment Initiation

Absolute Contraindications to Testosterone Therapy

Do not start testosterone therapy in patients with: 3, 7, 5

• 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
• Myocardial infarction or stroke within the last 6 months
• Thrombophilia
• Planning fertility in the near term

Treatment Goals and Formulations

• Aim for testosterone levels in the mid-normal range (350-750 ng/dL) during treatment 1, 6, 3, 5
• Choose formulation based on pharmacokinetics, treatment burden, and cost 6, 8, 5
• For testosterone gel 1.62%, the starting dose is 40.5 mg (2 pump actuations) applied once daily in the morning to shoulders and upper arms 3
• Apply to clean, dry, intact skin; avoid abdomen, genitals, chest, armpits, or knees 3
• Cover application site with clothing once dry and wash hands thoroughly with soap and water 3
• Avoid swimming or showering for minimum 2 hours after application 3

Dose Titration Protocol

Check pre-dose morning testosterone at 14 days and 28 days after starting treatment or dose adjustment: 3

• If testosterone >750 ng/dL: decrease dose by 20.25 mg
• If testosterone 350-750 ng/dL: continue current dose
• If testosterone <350 ng/dL: increase dose by 20.25 mg
• Dose range: 20.25 mg (minimum) to 81 mg (maximum) daily 3

Monitoring During Treatment

Regular Monitoring Parameters

• Evaluate symptoms, adverse effects, and compliance 5
• Measure serum testosterone and hematocrit concentrations 6, 5
• Monitor PSA in men over 40 years 6
• Assess prostate cancer risk during the first year after initiating therapy 5
• If breast symptoms or gynecomastia develop, measure serum estradiol 1, 6

Special Considerations for Fertility Preservation

For patients wishing to preserve fertility with low/normal LH levels: 1, 6

• Consider selective estrogen receptor modulators instead of testosterone therapy
• Alternatively, consider gonadotropin therapy (combination of hCG and FSH)
• Do not use testosterone therapy in men planning fertility in the near term 5

Lifestyle Modifications

• Weight loss through low-calorie diets can improve testosterone levels in obese patients with secondary hypogonadism 6
• Regular physical activity provides similar benefits, though testosterone increases are typically modest (1-2 nmol/L) 6
• Consider combining lifestyle modifications with testosterone therapy for better outcomes in symptomatic patients 6

Critical Safety Warning

Children must avoid contact with unwashed or unclothed application sites in men using testosterone gel, as virilization has been reported in secondarily exposed children. 3, 7