What is the best course of action for a patient with bioavailable testosterone level of 105.7 and free testosterone level of 56.2, indicating potential hypogonadism?

Interpretation of Testosterone Levels and Clinical Management

Direct Assessment of Your Laboratory Values

Your bioavailable testosterone of 105.7 ng/dL and free testosterone of 56.2 pg/mL are both frankly low and meet biochemical criteria for hypogonadism, warranting further diagnostic workup and potential treatment if you have specific symptoms. 1, 2

The discordance between your borderline-low total testosterone (which you haven't provided but is implied by these free/bioavailable values) and clearly low free testosterone confirms true biochemical hypogonadism 1. This pattern is common in men over 60 years, where 26.3% have normal total testosterone with low free testosterone—symptomatic hypogonadism that would be missed by screening with total testosterone alone 3.

Required Diagnostic Confirmation Steps

Before initiating any treatment, you must complete the following workup:

• Repeat morning testosterone measurements (8-10 AM) on at least two separate occasions to establish persistent hypogonadism, as single measurements are insufficient due to assay variability and diurnal fluctuation 1, 2, 4
• Measure serum LH and FSH to distinguish primary (testicular) from secondary (pituitary-hypothalamic) hypogonadism, which has critical treatment implications including fertility preservation 1
  • Elevated LH/FSH with low testosterone = primary hypogonadism 1
  • Low or low-normal LH/FSH with low testosterone = secondary hypogonadism 1
• Measure sex hormone-binding globulin (SHBG) to distinguish true hypogonadism from low SHBG-related decreases in total testosterone 1
• Obtain serum prolactin if loss of libido is present, to exclude hyperprolactinemia as a reversible cause 1

Symptom Assessment: What Matters for Treatment

Treatment is only indicated if you have specific hypogonadal symptoms—biochemical evidence alone is insufficient. 1, 2

Primary symptoms with proven benefit from testosterone therapy:

• Diminished libido and erectile dysfunction are the primary indications, with small but significant improvements (standardized mean difference 0.35) 1, 5
• Men with initial total testosterone 201-300 ng/dL showed 96.6% improvement in libido with testosterone replacement 5

Symptoms with minimal or no proven benefit:

• Fatigue, low energy, depressed mood, reduced physical function, or cognitive complaints show little to no improvement even with confirmed hypogonadism (effect sizes 0.17 for energy, -0.19 for mood) 1
• Do not expect meaningful improvements in physical functioning, energy, vitality, or cognition even if treatment is initiated 1

Treatment Algorithm If Hypogonadism Is Confirmed

Step 1: Fertility Considerations (Critical First Question)

• If you desire fertility preservation now or in the future, testosterone therapy is absolutely contraindicated as it causes azoospermia 1, 2
• Instead, you would require gonadotropin therapy (hCG plus FSH) for secondary hypogonadism 1

Step 2: First-Line Treatment Selection

Transdermal testosterone gel 1.62% at 40.5 mg daily is the preferred first-line formulation due to more stable day-to-day testosterone levels and lower erythrocytosis risk compared to injections 1, 4

• Apply once daily in the morning to clean, dry, intact skin of shoulders and upper arms 4
• Critical safety warning: Children and women must never touch application sites—secondary exposure causes virilization 4
• Wash hands immediately after application and cover sites with clothing after gel dries 4

Step 3: Alternative Injectable Option

If cost is a concern (transdermal costs $2,135/year vs. $156/year for injections), testosterone cypionate or enanthate 100-200 mg every 2 weeks is acceptable 1

• Higher risk of erythrocytosis (up to 44%) compared to transdermal preparations 1
• Measure testosterone levels midway between injections (days 5-7), targeting 500-600 ng/dL 1, 2

Step 4: Monitoring Requirements

Initial monitoring (first 3 months):

• Testosterone levels at 14 days and 28 days after starting treatment or dose adjustment 4
• Target mid-normal range of 500-600 ng/dL 1, 2

Ongoing monitoring (every 6-12 months once stable):

• Morning testosterone levels 1
• Hematocrit—withhold treatment if >54% and consider phlebotomy in high-risk cases 1, 2
• PSA levels in men over 40 years—refer for urologic evaluation if PSA increases >1.0 ng/mL in first 6 months or >0.4 ng/mL per year thereafter 1
• Digital rectal examination to assess for prostate abnormalities 1

Step 5: Reassessment at 12 Months

If no improvement in sexual function is seen at 12 months, discontinue testosterone to prevent unnecessary long-term exposure to potential risks without benefit 1

Absolute Contraindications to Treatment

Do not initiate testosterone therapy if you have:

• Active desire for fertility preservation 1, 2
• Active or treated male breast cancer 1
• Prostate cancer 1
• Hematocrit >54% 1, 2
• Untreated severe obstructive sleep apnea 1
• Recent myocardial infarction or stroke within past 3-6 months 1

Alternative Approach: Address Underlying Causes First

If you have obesity-associated secondary hypogonadism, attempt weight loss through low-calorie diets and regular exercise before initiating testosterone, as 5-10% weight loss can significantly increase endogenous testosterone production 1

Additional reversible causes to evaluate:

• Sleep disorders, thyroid dysfunction, anemia, vitamin D deficiency 1
• Metabolic syndrome and cardiovascular risk factors 1
• Medications (opiates, corticosteroids) 6

Critical Pitfalls to Avoid

• Never start testosterone based on symptoms alone without confirmed biochemical hypogonadism on two separate morning measurements 1, 2, 4
• Never assume you have primary hypogonadism without measuring LH/FSH—up to 25% of men on testosterone therapy may not have met diagnostic criteria initially 1
• Never ignore the fertility question—testosterone causes prolonged and potentially irreversible azoospermia 1
• Do not expect improvements in energy, physical function, or mood—these show minimal to no benefit even with confirmed hypogonadism 1