What is the best course of treatment for an elderly man with hypergonadotropic (elevated Luteinizing Hormone (LH)) hypogonadism and low testosterone levels?

Treatment of Hypergonadotropic Hypogonadism in an Elderly Man

Testosterone replacement therapy is the definitive treatment for an elderly man with elevated LH and low testosterone (primary/hypergonadotropic hypogonadism), with transdermal testosterone gel as the preferred first-line formulation, targeting modest improvements in sexual function while accepting minimal benefits for energy, physical function, or cognition. 1

Diagnostic Confirmation Required

Before initiating therapy, confirm the diagnosis with:

• Two separate morning testosterone measurements (8-10 AM) showing levels <300 ng/dL to establish persistent hypogonadism 1
• Elevated LH and FSH levels confirm primary (testicular) hypogonadism, distinguishing it from secondary (pituitary-hypothalamic) causes 1
• Free testosterone by equilibrium dialysis and sex hormone-binding globulin (SHBG) levels, especially important in elderly men with obesity 1

The elevated LH with low testosterone definitively indicates primary testicular failure—the testes cannot respond to gonadotropin stimulation, making this fundamentally different from secondary hypogonadism where gonadotropin therapy could restore fertility 1, 2

Treatment Selection Algorithm

First-Line: Transdermal Testosterone Gel

• Start with transdermal testosterone gel 1.62% at 40.5 mg daily as the preferred formulation for elderly men 1
• Provides more stable day-to-day testosterone levels compared to injections 1
• Lower risk of erythrocytosis (a critical concern in elderly patients) compared to injectable testosterone 1, 3
• Annual cost approximately $2,135 but offers convenience and ease of dose titration 1

Alternative: Intramuscular Testosterone

• Testosterone cypionate or enanthate 100-200 mg every 2 weeks if cost is a primary concern 1
• Annual cost only $156 versus $2,135 for transdermal preparations 1
• Higher risk of erythrocytosis (up to 44% with injections vs. lower rates with transdermal) 1, 3
• Causes fluctuating testosterone levels with peaks at days 2-5 and return to baseline by days 13-14 1

Realistic Treatment Expectations

Set clear expectations with the patient about limited benefits:

Proven Benefits (Small Effect Sizes)

• Sexual function and libido improvement with standardized mean difference of 0.35—this is the primary indication 4, 1
• Small improvements in quality of life, primarily driven by sexual function domains 4, 1

Minimal or No Benefits

• Little to no effect on physical functioning despite common patient expectations 4, 3
• Little to no improvement in energy, vitality, or fatigue (SMD only 0.17) 4, 1
• Minimal effect on depressive symptoms (SMD -0.19, less than clinically meaningful) 4, 1
• No benefit for cognition in elderly men 4, 3

The American College of Physicians evidence review makes clear that testosterone therapy in older men produces only modest improvements in sexual function, with effect sizes too small to be clinically meaningful for other age-related symptoms 4, 3

Absolute Contraindications

Do not initiate testosterone if any of the following are present:

• Active or treated male breast cancer 1, 5
• Hematocrit >54% (requires correction before starting therapy) 1
• Active desire for fertility preservation—though less relevant in elderly men, testosterone suppresses spermatogenesis and causes azoospermia 1
• Untreated severe obstructive sleep apnea 1
• Recent cardiovascular events within 3-6 months 1

Mandatory Baseline Testing

Before initiating testosterone therapy:

• Hematocrit or hemoglobin to establish baseline and screen for polycythemia 1, 5
• PSA level in men over 40 years (essentially all elderly men) 1
• Digital rectal examination to assess for palpable prostate nodules 1
• PSA >4.0 ng/mL requires urologic evaluation and documented negative prostate biopsy before starting therapy 1

Monitoring Protocol

Initial Phase (First 3 Months)

• Measure testosterone levels at 2-3 months after treatment initiation or any dose change 1
• Target mid-normal testosterone levels of 500-600 ng/dL 1
• For injectable testosterone, measure levels midway between injections (days 5-7 after injection) 1
• Check hematocrit for early detection of erythrocytosis 1, 5

Maintenance Phase (After Stabilization)

• Testosterone levels every 6-12 months once stable on a given dose 1
• Hematocrit monitoring periodically—withhold treatment if >54% and consider phlebotomy in high-risk cases 1
• PSA monitoring—urologic referral if PSA increases >1.0 ng/mL in first 6 months or >0.4 ng/mL per year thereafter 1

Critical Safety Concerns in Elderly Men

Cardiovascular Risk

• Low-certainty evidence suggests possible small increase in adverse cardiovascular events (Peto odds ratio 1.22) 3
• Long-term safety beyond 36 months has not been established, particularly concerning for elderly patients requiring lifelong therapy 3
• Injectable testosterone may carry higher cardiovascular risk than transdermal preparations due to supraphysiologic and subtherapeutic fluctuations 1

Erythrocytosis Risk

• Occurs in 2.8-17.9% of patients depending on formulation, with up to 44% risk with injectable testosterone 1, 3
• Elderly men are at higher baseline risk for polycythemia complications including thrombotic events 3
• Mandatory to withhold treatment if hematocrit exceeds 54% 1

Prostate Concerns

• Geriatric patients treated with androgens may be at increased risk for prostatic hypertrophy and prostatic carcinoma 5
• While testosterone therapy is not proven to cause prostate cancer, monitoring is essential 1

Treatment Discontinuation Criteria

Discontinue testosterone therapy at 12 months if no improvement in sexual function is observed, as this is the primary evidence-based indication for therapy 1

Other reasons to discontinue:

• Development of hematocrit >54% despite dose reduction 1
• Significant PSA increases requiring urologic evaluation 1
• Development of absolute contraindications (breast cancer, severe adverse effects) 1
• Patient preference due to lack of perceived benefit 1

Common Pitfalls to Avoid

• Do not prescribe testosterone for "age-related decline" alone without confirmed biochemical hypogonadism and specific symptoms 1
• Do not use testosterone to improve energy, vitality, or physical function in elderly men—evidence shows minimal to no benefit 4, 3
• Do not assume all elderly men with low testosterone need treatment—approximately 20-30% of men over 60 have low-normal testosterone without requiring therapy 1
• Do not start testosterone without baseline hematocrit and PSA in elderly men 1, 5
• Do not continue therapy beyond 12 months without documented improvement in sexual function 1

Special Consideration: Primary vs. Secondary Hypogonadism

The elevated LH in this patient confirms primary (hypergonadotropic) hypogonadism, meaning testicular failure 1, 6. This distinction is critical:

• Testosterone replacement is the only option for primary hypogonadism—the testes cannot respond to gonadotropin stimulation 1, 2
• Unlike secondary hypogonadism, gonadotropin therapy (hCG plus FSH) will not work because the problem is testicular, not pituitary 1, 2
• Fertility restoration is not possible with any therapy in primary hypogonadism, though this is less relevant in elderly men 1, 7

The elevated LH represents the pituitary's futile attempt to stimulate failed testes—a key pathophysiologic distinction from secondary hypogonadism where LH is low or inappropriately normal 1, 6