What are the treatment options for symptomatic low testosterone?

Treatment for Symptomatic Low Testosterone

Testosterone replacement therapy (TRT) is the first-line treatment for men with confirmed symptomatic hypogonadism, with transdermal preparations (gels/patches) preferred initially for more stable testosterone levels, though intramuscular injections are a more economical alternative. 1, 2

Diagnosis Requirements Before Treatment

Diagnosis requires BOTH biochemical confirmation AND clinical symptoms—never treat based on lab values alone 2:

• Biochemical criteria: Total testosterone <300 ng/dL on at least two separate morning measurements (drawn between 8-10 AM) 1, 2
• Required symptoms: Reduced libido, erectile dysfunction, diminished vitality/energy, fatigue, depression, poor concentration, or reduced work performance 1, 2
• Additional testing: Measure LH and FSH to distinguish primary (testicular) from secondary (pituitary-hypothalamic) hypogonadism 1
• Special considerations: Check prolactin if LH is low/normal, and estradiol if gynecomastia is present 2

Treatment Options and Selection Algorithm

First-Line: Transdermal Testosterone (Gels/Patches)

Transdermal preparations are preferred for initial therapy due to stable day-to-day testosterone levels and lower risk of erythrocytosis 1:

• Dosing: Testosterone gel 1.62% starting dose is 40.5 mg daily (2 pump actuations), applied to shoulders and upper arms 3
• Application: Apply once daily in the morning after showering to clean, dry skin of shoulders/upper arms only 3
• Cost: Approximately $2,135 annually 2
• Advantages: More stable levels, convenient, preferred by many patients for ease of use 1
• Critical safety warning: Risk of secondary exposure to children and women—application sites must be covered with clothing after drying, and patients must wash hands immediately after application 3

Alternative: Intramuscular Injections

Choose intramuscular injections when cost is a primary concern or patient preference favors less frequent dosing 1, 2:

• Formulations: Testosterone cypionate or enanthate administered every 2-3 weeks 1
• Cost: Approximately $156 annually—significantly more economical than topical preparations 2
• Pharmacokinetics: Peak levels occur 2-5 days post-injection, with return to baseline at 10-14 days 1
• Disadvantage: Higher risk of erythrocytosis (up to 44% vs 3-18% with transdermal) and fluctuating testosterone levels that may cause mood/sexual function variability 1, 2

Expected Benefits of TRT

The American College of Physicians and European Association of Urology define realistic treatment expectations 1, 2:

• Sexual function: Small but significant improvements in libido and erectile function 1, 2
• Metabolic effects: Improvements in fasting glucose, insulin resistance, triglycerides, and HDL cholesterol 1
• Body composition: Increased muscle mass and strength, reduced fat mass 2
• Bone health: Improved bone mineral density 2
• Mood/energy: Modest improvements in vitality, fatigue, and depressive symptoms 1, 2
• Limited benefits: Little to no effect on physical functioning or cognition, particularly in elderly men 1

Monitoring Protocol

Initial Monitoring

• Testosterone levels: Check at 2-3 months after initiation or any dose adjustment 1, 2
• Target level: Mid-normal range (500-600 ng/dL) 1
• For injections: Measure midway between injections 1
• For transdermal: Can measure at any time due to stable levels 1

Ongoing Monitoring

• Testosterone levels: Every 6-12 months once stable 1, 2
• Symptom reassessment: Within 12 months and periodically thereafter—discontinue if no improvement in sexual function after 12 months 1, 2
• Hematocrit monitoring: Screen for erythrocytosis, especially with injectable formulations 1, 2

Absolute Contraindications

Do not prescribe TRT in the following situations 2, 3:

• Active or treated male breast cancer 2
• Known or suspected prostate cancer 2, 3
• Men actively seeking fertility (standard TRT suppresses spermatogenesis) 1, 2
• Pregnancy in female partners (risk of virilization) 3

Relative Contraindications/Precautions

Exercise caution and consider alternative treatments in 2:

• Recent cardiovascular disease 2
• Untreated severe sleep apnea 3
• Severe heart failure 3
• Baseline elevated hematocrit 1
• Severe lower urinary tract symptoms from benign prostatic hyperplasia 3

Alternative Treatments for Fertility Preservation

For men with secondary hypogonadism who wish to preserve fertility, use selective estrogen receptor modulators (SERMs) or gonadotropin therapy instead of standard TRT 2, 4:

• SERMs: Stimulate endogenous testosterone production without suppressing spermatogenesis 2
• Gonadotropin therapy: Directly stimulates testicular function 2
• These alternatives avoid the negative feedback on the hypothalamic-pituitary-gonadal axis that occurs with exogenous testosterone 4

Lifestyle Modifications as Adjunctive Therapy

Weight loss through low-calorie diets and regular physical activity can improve testosterone levels in obese men with secondary hypogonadism 1, 2:

• These interventions should be recommended alongside TRT, particularly in men with obesity-associated hypogonadism 1, 2

Common Pitfalls to Avoid

• Never treat based on age alone: TRT is not indicated for "age-related hypogonadism" without confirmed low testosterone AND symptoms 1, 3
• Never use in eugonadal men: TRT should never be prescribed to men with normal testosterone levels 1
• Secondary exposure prevention: Failure to counsel patients about covering application sites and washing hands leads to virilization in children and women 3
• Premature discontinuation: Patients may not see full benefits until 12 months of therapy 2