Is testosterone replacement therapy (TRT) a lifelong commitment for a male patient with confirmed biochemical hypogonadism and symptoms of testosterone deficiency?

Is Testosterone Replacement Therapy Lifelong?

No, testosterone replacement therapy does not have to be lifelong—discontinuation is appropriate and common when there is no improvement in sexual function after 12 months, when side effects develop, or when fertility is desired. 1

Evidence for Discontinuation

The American College of Physicians explicitly recommends stopping TRT if sexual function has not improved after 12 months of treatment, as sexual dysfunction is the primary evidence-based indication for therapy. 1 Discontinuation rates of 30-62% have been reported in clinical practice, demonstrating that stopping therapy is both common and clinically acceptable. 1

Testosterone levels return to baseline within 10-14 days after stopping injectable testosterone (cypionate or enanthate) and within days of discontinuing transdermal preparations. 1 This rapid return to baseline contradicts the notion that TRT must be permanent once started.

When to Consider Stopping TRT

Primary Indication: Lack of Benefit

• Discontinue if no improvement in sexual function after 12 months, as this is the only outcome with robust evidence for benefit (standardized mean difference 0.35). 1, 2
• TRT produces little to no effect on physical functioning, energy, vitality, depressive symptoms, or cognition—even in confirmed hypogonadism. 2, 3

Safety Concerns Requiring Discontinuation

• Erythrocytosis with hematocrit >54% requires immediate cessation and consideration of phlebotomy. 1, 2
• Significant PSA elevation requiring urologic evaluation mandates stopping therapy. 1
• Active or treated male breast cancer is an absolute contraindication. 1, 2
• Active desire for fertility, as TRT suppresses spermatogenesis and causes azoospermia. 1, 2

Post-Discontinuation Management

Monitoring After Stopping

• Reevaluate symptoms within 12 months to determine if hypogonadal symptoms return or if improvement persists off therapy. 1
• Check testosterone levels 2-3 months after stopping to confirm return to baseline. 1
• Measure LH and FSH levels to assess recovery of the hypothalamic-pituitary-gonadal axis. 1
• Monitor for recovery of spermatogenesis if fertility is desired (typically requires 3-6 months). 1

Alternative Approaches if Symptoms Return

For men with secondary hypogonadism who desire fertility preservation:

• Human chorionic gonadotropin (hCG) plus FSH stimulates endogenous testosterone production while preserving testicular function. 2, 1
• Selective estrogen receptor modulators (SERMs) or aromatase inhibitors may be considered as alternatives to exogenous testosterone. 1, 4

For men with obesity-associated secondary hypogonadism:

• Weight loss through low-calorie diets and regular exercise can improve testosterone levels without medication. 2, 1

Critical Pitfalls to Avoid

Never assume patients need lifelong therapy without reassessing benefit. 1 The evidence shows that hormonal baseline can be restored after stopping, and many men do not experience return of symptoms. 1

Never continue TRT indefinitely without periodic reassessment of sexual function, as this is the only outcome with proven benefit. 1, 2

Never start TRT without confirming the patient does not desire fertility, as suppression of spermatogenesis can be prolonged even after discontinuation. 2, 1

Duration of Therapy Considerations

While some men with permanent primary hypogonadism (testicular failure) may require long-term therapy, the decision to continue TRT should be based on sustained clinical benefit, not an assumption of lifelong necessity. 1 The 2024 TRAVERSE trial demonstrated sustained improvements in sexual activity at 24 months in responders, but this does not mean all men require indefinite treatment. 5

For men with secondary hypogonadism, reversible causes should be addressed first (obesity, metabolic syndrome, medications, sleep apnea), as these may eliminate the need for long-term TRT. 2, 1