What is the best approach for initiating testosterone therapy in a patient with hypogonadism and low testosterone levels?

Initiate Testosterone Replacement Therapy for This Patient

This 67-year-old man meets diagnostic criteria for primary hypogonadism and should be started on testosterone replacement therapy, with transdermal testosterone gel 1.62% at 40.5 mg daily as the preferred first-line formulation. 1

Diagnostic Confirmation

Your patient has confirmed biochemical hypogonadism with the following evidence:

• Two separate morning testosterone measurements of 131 ng/dL and 129 ng/dL, both well below the diagnostic threshold of 275-300 ng/dL 1, 2
• Elevated FSH (38.7) and LH (11.9) with low testosterone confirms primary (testicular) hypogonadism rather than secondary hypogonadism 1, 2
• Normal PSA (0.79) indicates no contraindication to testosterone therapy 1

The elevated gonadotropins distinguish this as primary testicular failure, meaning the testes are not responding to pituitary signals—this is critical because it means fertility preservation is not an option (unlike secondary hypogonadism where gonadotropin therapy could restore spermatogenesis). 1

Treatment Selection Algorithm

First-Line: Transdermal Testosterone Gel

Start with transdermal testosterone gel 1.62% at 40.5 mg daily (2 pump actuations or one 40.5 mg packet) applied to shoulders and upper arms each morning. 1, 3

Rationale for choosing transdermal over injectable:

• More stable day-to-day testosterone levels compared to the peaks and troughs of injections 1, 2
• Lower risk of erythrocytosis (elevated hematocrit) compared to injectable testosterone 1
• Better for older patients who may have cardiovascular risk factors 1

Alternative: Injectable Testosterone (If Cost is Prohibitive)

If the patient cannot afford transdermal gel ($2,135 annually vs $156 for injections), use testosterone cypionate or enanthate 100-200 mg intramuscularly every 2 weeks. 1, 2

• Measure testosterone levels midway between injections (day 7 if dosing every 2 weeks) 1, 2
• Target mid-normal range of 500-600 ng/dL 1, 2
• Be aware that injectable forms carry higher erythrocytosis risk, particularly important in a 67-year-old 1

Pre-Treatment Counseling: Set Realistic Expectations

Primary benefits (small but significant):

• Improved sexual function and libido (standardized mean difference 0.35) 1
• Small improvements in quality of life, primarily in sexual domains 1

Minimal or no benefits:

• Little to no effect on physical functioning, energy, vitality, or cognition 1
• Minimal improvements in depressive symptoms (SMD -0.19) 1
• Effect sizes for energy and fatigue are barely distinguishable from placebo (SMD 0.17) 1

This is crucial: The European Association of Urology explicitly states that testosterone produces "only small improvements in sexual function and quality of life, with little to no effect on physical functioning, depressive symptoms, energy, or cognition." 1 Many patients expect dramatic improvements in energy and vitality that simply do not occur.

Monitoring Protocol

Initial Phase (First 3 Months)

• Testosterone levels at 2-3 months after starting therapy or after any dose adjustment 1, 2
• For transdermal: measure any morning sample 1
• For injectable: measure midway between injections 1, 2
• Target range: 500-600 ng/dL (mid-normal) 1, 2

Dose Adjustment

• Transdermal gel can be adjusted between 20.25 mg (1 pump) and 81 mg (4 pumps) daily 1, 3
• Injectable can be adjusted between 50-400 mg every 2-4 weeks 1

Long-Term Monitoring (Every 6-12 Months)

• Hematocrit/hemoglobin: Withhold treatment if hematocrit >54% and consider phlebotomy 1
• PSA: Monitor in all men over 40; significant increases warrant evaluation 1
• Digital rectal exam: Assess for benign prostatic hyperplasia symptoms 1
• Testosterone level: Confirm stable therapeutic range 1, 2

Critical 12-Month Reassessment

Reevaluate symptoms at 12 months and discontinue testosterone if no improvement in sexual function is seen. 1 This prevents unnecessary long-term exposure to potential risks without benefit.

Absolute Contraindications to Verify

Before prescribing, confirm the patient does NOT have:

• Active or treated male breast cancer 1
• Active desire for fertility preservation (though at 67 with primary hypogonadism, this is unlikely) 1
• Prostate cancer 1
• Hematocrit >54% 1
• Untreated severe obstructive sleep apnea 1

Safety Counseling for Transdermal Gel

Critical secondary exposure prevention (FDA boxed warning):

• Wash hands immediately with soap and water after application 3
• Cover application sites with clothing after gel dries 3
• Wash application site thoroughly with soap and water before any skin-to-skin contact with others 3
• Children and women must avoid contact with unwashed or unclothed application sites 3
• Virilization has been reported in children secondarily exposed to testosterone gel 3

Common Pitfalls to Avoid

1. Do not assume this patient will experience dramatic improvements in energy or mood—the evidence shows minimal effects in these domains even with confirmed hypogonadism 1

2. Do not skip the 12-month reassessment—if sexual function hasn't improved, continuing therapy exposes the patient to risks (erythrocytosis, cardiovascular events) without benefit 1

3. Do not use weekly injectable dosing—this exceeds standard practice and increases risk of supraphysiologic levels and erythrocytosis 1

4. Do not neglect hematocrit monitoring—erythrocytosis risk is up to 44% with injectable testosterone in older men 1

5. For this patient with primary hypogonadism, do not waste time investigating reversible causes—the elevated FSH/LH confirms permanent testicular failure 1, 2