What is the role of testosterone tablets in treating hypogonadism (low testosterone) in adult males?

Testosterone Tablets for Low Testosterone

For men with confirmed hypogonadism (morning testosterone <300 ng/dL on two separate occasions plus symptoms), oral testosterone undecanoate is an FDA-approved option, but intramuscular injections ($156/year) or transdermal gels ($2,135/year) remain preferred first-line treatments due to better-established safety profiles and more stable testosterone levels. 1, 2

Diagnostic Requirements Before Any Testosterone Treatment

You must confirm both biochemical hypogonadism AND symptoms before initiating any testosterone formulation:

• Measure morning (8-10 AM) total testosterone on two separate occasions, with levels <300 ng/dL indicating hypogonadism 1, 3
• Document specific symptoms: diminished libido, erectile dysfunction, reduced energy, decreased strength/endurance, or deterioration in work performance 4, 1
• Measure LH and FSH to distinguish primary (elevated LH/FSH) from secondary (low/normal LH/FSH) hypogonadism, as this determines fertility preservation options 1, 5

Critical pitfall: Never start testosterone based on symptoms alone—approximately 20-30% of men currently receiving testosterone in the U.S. lack documented low testosterone levels, violating evidence-based guidelines 1

Oral Testosterone Undecanoate (Tablets): FDA-Approved but Second-Line

FDA Labeling and Boxed Warning

The FDA-approved oral testosterone undecanoate carries a black box warning for blood pressure increases that can elevate risk of major adverse cardiovascular events (MACE), including non-fatal MI, stroke, and cardiovascular death 3. Due to this cardiovascular risk, the FDA explicitly restricts its use to men with hypogonadism from structural or genetic etiologies only—not age-related hypogonadism 3.

Dosing and Monitoring for Oral Tablets

• Starting dose: 200 mg orally twice daily (morning and evening) with food 3
• Check testosterone levels 7 days after starting, drawn 3-5 hours after morning dose 3
• Adjust dose from minimum 100 mg once daily to maximum 400 mg twice daily based on serum levels 3
• Monitor blood pressure before initiation and periodically throughout treatment 3

Why Oral Tablets Are Second-Line

The European Association of Urology recommends transdermal testosterone gel as the preferred first-line formulation for confirmed hypogonadism, not oral tablets 1. The American College of Physicians guideline similarly prioritizes intramuscular injections and transdermal preparations over oral formulations 4, 2.

Preferred First-Line Treatment Options

Intramuscular Injections: Most Cost-Effective

• Testosterone cypionate or enanthate 100-200 mg every 2 weeks (or 50 mg weekly for more stable levels) 1, 5
• Annual cost: $156.24 vs. $2,135.32 for transdermal 4, 1, 2
• Peak levels occur days 2-5, return to baseline by days 10-14 5
• Measure testosterone midway between injections (days 5-7), targeting 500-600 ng/dL 1, 5
• Higher risk of erythrocytosis (up to 44%) compared to transdermal (3-18%) 1, 5

Transdermal Gel: Most Stable Levels

• Transdermal testosterone gel 1.62% at 40.5 mg daily is the European guideline-recommended first-line option 1
• Provides more stable day-to-day testosterone levels compared to injections 1, 5
• Patient preference studies show 71% prefer topical gel over injections for convenience, ease of use, and non-staining of clothes 4, 2
• Lower erythrocytosis risk than injections 1, 5

Expected Treatment Outcomes: Set Realistic Expectations

Small but significant improvements in sexual function only—testosterone produces minimal benefits for other symptoms:

• Sexual function and libido: Small improvement (standardized mean difference 0.35) 1, 2
• Energy and vitality: Minimal improvement (SMD 0.17)—barely distinguishable from placebo 1, 2
• Depressive symptoms: Less-than-small improvement (SMD -0.19) 1, 2
• Physical functioning, cognition: Little to no effect 4, 1, 2

The American College of Physicians recommends re-evaluating symptoms at 12 months and discontinuing testosterone if no improvement in sexual function occurs, to prevent unnecessary long-term exposure without benefit 1, 2.

Absolute Contraindications to All Testosterone Formulations

• Active or treated male breast cancer 1, 3
• Men actively seeking fertility—testosterone suppresses spermatogenesis and causes prolonged azoospermia; use gonadotropin therapy (hCG plus FSH) instead 1, 5, 3
• Hematocrit >54% 1, 3
• Pregnancy in female partners (testosterone causes fetal virilization) 3
• Age-related hypogonadism without structural/genetic etiology (for oral testosterone undecanoate specifically) 3

Monitoring Requirements During Treatment

• Testosterone levels at 2-3 months, then every 6-12 months once stable 1, 5
• Hematocrit every 3 months—withhold treatment if >54% and consider phlebotomy 1, 3
• PSA in men over 40 years before starting and periodically during treatment 1, 5
• Blood pressure monitoring (especially critical for oral testosterone undecanoate) 3

Treatment Algorithm

1. Confirm diagnosis: Two morning testosterone levels <300 ng/dL plus symptoms (especially diminished libido/erectile dysfunction) 1, 3
2. Assess fertility desires: If seeking fertility, use gonadotropin therapy instead of testosterone 1, 5
3. Check contraindications: Exclude breast/prostate cancer, hematocrit >54%, recent cardiovascular events 1, 3
4. Select formulation based on priorities:
   • Cost priority: Intramuscular testosterone cypionate 100-200 mg every 2 weeks 4, 1, 2
   • Stable levels priority: Transdermal gel 40.5 mg daily 1
   • Oral preference with structural/genetic hypogonadism: Testosterone undecanoate 200 mg twice daily with food (but recognize higher cardiovascular risk) 3
5. Monitor response at 12 months: Discontinue if no improvement in sexual function 1, 2

Bottom line: While oral testosterone tablets are FDA-approved, intramuscular injections offer the best cost-effectiveness ($156 vs. $2,135 annually), and transdermal gels provide the most stable testosterone levels with lower erythrocytosis risk—both are preferred over oral formulations by major guidelines 4, 1, 2.