What is the primary treatment for hypogonadism (low testosterone)?

Treatment for Low Testosterone (Hypogonadism)

Primary Treatment Recommendation

Testosterone replacement therapy (TRT) is the first-line treatment for confirmed hypogonadism, with transdermal testosterone gel (40.5 mg daily) as the preferred initial formulation due to more stable day-to-day testosterone levels. 1, 2

Diagnostic Confirmation Before Treatment

Before initiating any testosterone therapy, you must confirm the diagnosis:

• Measure morning total testosterone (between 8-10 AM) on at least two separate days to confirm levels are consistently below 300 ng/dL 1, 3
• Measure free testosterone by equilibrium dialysis and sex hormone-binding globulin (SHBG), especially in men with obesity 1
• Check serum LH and FSH levels to distinguish primary hypogonadism (elevated LH/FSH) from secondary hypogonadism (normal or low LH/FSH) 1
• Confirm presence of symptoms: diminished libido, erectile dysfunction, decreased sense of vitality, or muscle weakness 1, 4

Treatment Algorithm by Clinical Scenario

For Men NOT Seeking Fertility Preservation

Start with transdermal testosterone gel 40.5 mg daily (2 pump actuations) applied to shoulders and upper arms 1, 2

Alternative option: Intramuscular testosterone cypionate or enanthate every 2-3 weeks if cost is a primary concern (annual cost $156.24 vs $2,135.32 for transdermal) 1, 5

For Men Seeking Fertility Preservation

Testosterone replacement therapy is absolutely contraindicated 1, 6

Use clomiphene citrate instead for men with secondary hypogonadism, as it stimulates endogenous testosterone production without suppressing spermatogenesis 6

For secondary hypogonadism with fertility goals: Use recombinant human chorionic gonadotropin (hCG) plus FSH for optimal fertility preservation outcomes 1

Monitoring Requirements

Initial Monitoring Phase

• Check testosterone levels at 14 days and 28 days after starting treatment or after any dose adjustment 1, 2
• For transdermal gel: Target mid-normal testosterone levels (500-600 ng/dL) 1
• For intramuscular injections: Measure levels midway between injections, targeting 500-600 ng/dL 1

Dose Adjustment Protocol for Transdermal Gel

• If pre-dose morning testosterone >750 ng/dL: Decrease by 20.25 mg (1 pump actuation) 2
• If testosterone 350-750 ng/dL: Continue current dose 2
• If testosterone <350 ng/dL: Increase by 20.25 mg (1 pump actuation) 2
• Maximum dose: 81 mg (4 pump actuations) 2

Long-Term Monitoring

• Once stable on a given dose, monitor every 6-12 months 1
• Check hematocrit periodically; withhold treatment if >54% and consider phlebotomy in high-risk cases 1
• Monitor PSA levels in men over 40 years 1
• Assess for benign prostatic hyperplasia symptoms through prostate examination 1

Expected Treatment Outcomes

Benefits You Can Promise

• Small but significant improvements in sexual function and libido 1, 6
• Improvements in fasting plasma glucose, insulin resistance, triglyceride levels, and HDL cholesterol 1
• Potential improvement in bone mineral density 1
• May help correct mild anemia 1

Limited or No Benefits (Set Realistic Expectations)

• Little to no effect on physical functioning 1, 6
• Little to no improvement in depressive symptoms 1, 6
• Minimal effect on energy, vitality, or cognition 1, 6

If no improvement in sexual function after 12 months, discontinue treatment 1

Absolute Contraindications

• Men actively seeking fertility (use gonadotropins instead) 1
• Active or treated male breast cancer 1
• Men with prostate cancer (though evidence is evolving) 1
• Eugonadal men (even for weight loss, cardiometabolic improvement, cognition, vitality, or physical strength) 1, 7

Potential Risks and Side Effects

Higher Risk with Injectable Testosterone

• Erythrocytosis (elevated hematocrit) - higher risk with intramuscular injections compared to transdermal preparations 1, 2

Common to All Formulations

• Fluid retention 1
• Potential worsening of benign prostatic hyperplasia 1
• Sleep apnea 1
• Gynecomastia 1
• Acne or oily skin 1
• Testicular atrophy and infertility due to suppression of the hypothalamic-pituitary-gonadal axis 1, 8

Critical Safety Warning for Transdermal Gel

Children must avoid contact with unwashed or unclothed application sites due to risk of virilization from secondary exposure 2

Clomiphene Citrate as Alternative Treatment

When to Consider Clomiphene

• Men with secondary hypogonadism who wish to preserve fertility 6
• Men with obesity-related hypogonadism where increased aromatization of testosterone to estradiol suppresses LH 6
• Cost-conscious patients seeking effective treatment 6

Clomiphene Advantages

• Preserves fertility by maintaining or improving spermatogenesis 6
• Lower risk of polycythemia compared to testosterone replacement 6
• Achieves similar or superior outcomes for sexual function and quality of life 6

When NOT to Use Clomiphene

• Primary testicular failure - check baseline LH and FSH first 6
• Secondary hypogonadism that fails to respond after 3 months - switch to testosterone replacement 6
• When fertility preservation is not a concern 6

Common Pitfalls to Avoid

• Do not treat based on symptoms alone without laboratory confirmation of low testosterone on two separate morning measurements 7
• Do not use testosterone in eugonadal men even if they have symptoms like fatigue or low libido 1, 7
• Do not fail to distinguish between primary and secondary hypogonadism, as this determines whether clomiphene is an option 1, 6
• Do not apply transdermal gel to abdomen, genitals, chest, armpits, or knees - only shoulders and upper arms 2