What treatment options are available for a patient with low testosterone levels?

Treatment Options for Low Testosterone

For a patient with confirmed low testosterone, testosterone replacement therapy (TRT) is the first-line treatment, with transdermal testosterone gel (40.5 mg daily) preferred initially due to more stable testosterone levels, though intramuscular testosterone injections (50-400 mg every 2-4 weeks) are a more economical alternative. 1, 2

Diagnostic Confirmation Required Before Treatment

Before initiating any treatment, you must confirm the diagnosis properly:

• Measure morning total testosterone (between 8-10 AM) on at least two separate occasions, with levels below 300 ng/dL establishing hypogonadism 1, 3
• Confirm the patient has specific symptoms of testosterone deficiency, particularly diminished libido, erectile dysfunction, or reduced sense of vitality—symptoms alone without biochemical confirmation are insufficient 1, 3
• Measure serum LH and FSH levels to distinguish primary (testicular) from secondary (pituitary-hypothalamic) hypogonadism, as this critically impacts treatment selection 1, 3
• In borderline cases, measure free testosterone by equilibrium dialysis and sex hormone-binding globulin (SHBG), especially in men with obesity 1

First-Line Treatment Options

Transdermal Testosterone Gel (Preferred Initial Option)

• Start with transdermal testosterone gel 1.62% at 40.5 mg daily, which provides more stable day-to-day testosterone levels compared to injections 1
• Annual cost is approximately $2,135, making it more expensive but preferred for convenience and ease of use 1
• Skin reactions occur in approximately 5% of patients using gels 3

Intramuscular Testosterone Injections (More Economical Alternative)

• Testosterone cypionate or enanthate 50-400 mg every 2-4 weeks is FDA-approved dosing 1, 2
• Peak serum levels occur 2-5 days after injection, with return to baseline by days 10-14, supporting the 2-4 week dosing interval 1
• Annual cost is approximately $156, making it significantly more economical than transdermal preparations 1
• Higher risk of erythrocytosis (up to 44%) compared to transdermal preparations 1
• Inject deeply into the gluteal muscle, avoiding intravascular injection 2

Critical Pre-Treatment Assessment

Before starting TRT, you must evaluate for absolute contraindications:

• Active male breast cancer is an absolute contraindication 1, 3
• Men actively seeking fertility must not receive testosterone—instead, offer gonadotropin therapy (hCG plus FSH) for secondary hypogonadism, as testosterone causes azoospermia 1, 3
• Assess cardiovascular disease risk factors and measure baseline hemoglobin/hematocrit to monitor for polycythemia 3
• Perform digital rectal examination and measure PSA before initiating treatment in men over 40 years 1, 3
• Evaluate for sleep apnea by history 3

Monitoring During Treatment

Initial Monitoring Phase

• Check testosterone levels 2-3 months after treatment initiation or any dose change 1, 3
• For intramuscular injections, measure levels midway between injections, targeting a mid-normal value (500-600 ng/dL) 1
• Schedule first follow-up at 1-2 months to assess efficacy and consider dose adjustments 3

Long-Term Monitoring

• Once stable levels are confirmed, monitor every 6-12 months 1, 3
• At each visit, assess hematocrit and withhold treatment if >54%—consider phlebotomy in high-risk cases 1, 3
• Monitor PSA levels in men over 40 years and adjust treatment if significant increases occur 1, 3
• Assess for benign prostatic hyperplasia symptoms through prostate examination 1

Expected Treatment Outcomes

Set realistic expectations with your patient:

• Small but significant improvements in sexual function and libido are the primary benefits (standardized mean difference 0.35) 1, 4
• Little to no effect on physical functioning, energy, vitality, or cognition, even in confirmed hypogonadism 1
• Modest improvements in quality of life, particularly in vitality and social functioning domains 1
• Improvements in fasting plasma glucose, insulin resistance, triglyceride levels, and HDL cholesterol can be expected 1
• May help correct mild anemia 1
• Potential improvement in bone mineral density 1

Reevaluation Strategy

• If no improvement in sexual function after 12 months, discontinue treatment to prevent unnecessary long-term exposure to potential risks without benefit 1

Special Considerations for Secondary Hypogonadism

If your patient has secondary hypogonadism (low testosterone with low-normal LH/FSH):

• Consider gonadotropin therapy (hCG plus FSH) as first-line treatment if fertility preservation is desired, as this stimulates the testes directly and can restore both testosterone levels and fertility potential 1
• Measure serum prolactin in patients with low testosterone and low/normal LH levels to screen for hyperprolactinemia 3
• Consider pituitary MRI for patients with total testosterone <150 ng/dL and low/normal LH regardless of prolactin levels 3

Alternative Approaches Before TRT

For men with obesity-associated secondary hypogonadism:

• Weight loss through low-calorie diets can improve testosterone levels 1
• Regular physical activity and exercise should be encouraged 1
• Evaluate for sleep disorders, thyroid dysfunction, anemia, vitamin D deficiency as reversible causes 1

Common Pitfalls to Avoid

• Never start testosterone without confirming the patient does not desire fertility, as testosterone permanently compromises fertility by suppressing the hypothalamic-pituitary-gonadal axis 1, 3
• Never diagnose hypogonadism based on symptoms alone—approximately 20-30% of men receiving testosterone in the United States do not have documented low testosterone levels before treatment initiation 1
• Never use testosterone therapy in eugonadal men (normal testosterone levels), even for weight loss, cardiometabolic improvement, cognition, vitality, or physical strength 1
• Never attempt to diagnose the type of hypogonadism while the patient is on testosterone therapy, as results will be misleading—testosterone must be discontinued with adequate washout (2-4 weeks) before diagnostic testing 1
• Use testosterone cautiously in men with congestive heart failure or renal insufficiency due to potential fluid retention 3