Should testosterone be cycled?

Testosterone Therapy Should Not Be Cycled

Testosterone therapy should not be cycled but rather maintained at consistent levels within the middle tertile of the normal reference range (450-600 ng/dL) to achieve optimal clinical benefits while minimizing risks. 1

Evidence-Based Approach to Testosterone Therapy

Dosing and Administration

• Testosterone therapy should aim to achieve physiologic levels in the middle tertile of the normal range (450-600 ng/dL) using the minimal effective dose 1
• Consistent rather than cyclical administration is recommended to maintain stable hormone levels and symptom control 1
• Therapy should be continued only if clinical benefits (improved symptoms/signs) are observed; discontinuation is recommended if target levels are reached without symptom improvement 1

Monitoring Requirements

• Regular monitoring of testosterone levels is essential to ensure maintenance within target range 1, 2
• Hematocrit should be monitored to detect polycythemia, a potential adverse effect of testosterone therapy 1, 2
• Prostate-specific antigen (PSA) testing is necessary for men at risk of prostate cancer 2
• Patients should report any cardiovascular symptoms (chest pain, shortness of breath, dizziness) during follow-up visits 1

Safety Considerations

Cardiovascular Safety

• Recent high-quality evidence shows testosterone replacement therapy is noninferior to placebo regarding major adverse cardiovascular events in men with hypogonadism and preexisting or high risk of cardiovascular disease 3
• Testosterone therapy should not be initiated for at least 3-6 months after a cardiovascular event 1
• Patients with heart failure require careful monitoring for fluid retention, with testosterone levels maintained in the mid-range (350-600 ng/dL) 1

Fertility Implications

• Exogenous testosterone significantly suppresses spermatogenesis and should not be prescribed to men trying to conceive 1
• For men with hypogonadism who wish to maintain fertility, alternative therapies such as aromatase inhibitors, human chorionic gonadotropin, or selective estrogen receptor modulators should be considered 1

Rationale Against Cycling Testosterone

Physiological Considerations

• Natural testosterone production follows a diurnal rhythm but does not naturally "cycle" with prolonged periods of high and low levels 1, 2
• Cycling testosterone can lead to fluctuating symptoms during low periods and potentially increased side effects during high-dose periods 4
• Research on testosterone cycling shows minimal benefits and potential risks, with some subjects experiencing adverse psychological effects at higher doses (500 mg/week) 4

Clinical Evidence

• Short-term use (3-6 weeks) of testosterone can produce ergogenic effects, but this approach is not medically indicated for treating hypogonadism 5
• The goal of therapeutic testosterone replacement is symptom improvement through consistent physiologic levels, not intermittent supraphysiologic dosing 1
• Cycling may lead to inconsistent symptom control and potentially increase risks of adverse effects during high-dose periods 6, 4

Common Pitfalls to Avoid

• Using alkylated oral testosterone preparations, which are associated with liver toxicity 1
• Failing to monitor testosterone levels, hematocrit, and PSA during therapy 2
• Prescribing compounded testosterone products when FDA-approved formulations are available 1
• Initiating testosterone therapy in men actively trying to conceive 1
• Starting testosterone too soon after cardiovascular events (wait 3-6 months) 1, 2

Adjunctive Recommendations

• Lifestyle modifications (weight loss, increased physical activity) should be recommended alongside testosterone therapy to potentially increase endogenous testosterone levels and reduce cardiovascular risk 1
• Transdermal preparations (gels, patches) provide more stable day-to-day testosterone levels compared to injectable formulations 1, 6
• For patients with obesity and hypogonadism, testosterone replacement has shown favorable metabolic effects including improvements in insulin resistance and body composition 1