What are the guidelines for using testosterone supplements, such as AndroGel (testosterone) or Testim (testosterone), for treating low testosterone levels?

Testosterone Supplementation Guidelines

Testosterone therapy should only be initiated in men with documented low testosterone levels (<275-320 ng/dL on two fasting morning measurements) due to structural or genetic causes of hypogonadism—NOT for age-related low testosterone alone. 1

FDA-Approved Indications vs. Common Use

The FDA explicitly requires that all testosterone products (including AndroGel and Testim) be labeled for use only in men with hypogonadism from known structural or genetic causes (testicular failure, hypothalamic-pituitary injury). 1 The FDA specifically states that testosterone is contraindicated for "age-related hypogonadism" not associated with structural or genetic etiologies. 1

Despite this, most current testosterone use in the United States is for age-related low testosterone—a practice that exceeds FDA approval and lacks strong evidence for benefit. 1

When to Consider Testosterone Therapy

For Sexual Function Only (Conditional Recommendation)

If you decide to prescribe testosterone for age-related low testosterone, limit the indication to improving sexual function, as this is the only outcome with demonstrated benefit. 1

• Testosterone produces only small improvements in sexual function (standardized mean difference 0.35) and quality of life. 1, 2
• The quality of life improvement is primarily driven by effects on the sexual subscale, not overall well-being. 1
• Effect sizes are small and may not reach clinically meaningful thresholds for many patients. 1

When NOT to Prescribe

Do not initiate testosterone therapy to improve energy, vitality, physical function, or cognition—the evidence shows little to no benefit for these outcomes. 1

• Energy and vitality showed less-than-small improvements (SMD 0.17). 1
• Physical function showed no meaningful benefit. 1, 2
• Depressive symptoms improved by less-than-small amounts (SMD 0.19), and most men studied did not have baseline depression. 1
• Cognitive function showed no differences across multiple scales. 1

Formulation Selection: Intramuscular vs. Transdermal

When initiating therapy, prefer intramuscular testosterone over transdermal formulations (AndroGel, Testim) due to substantially lower cost and equivalent clinical effectiveness and safety. 1

• No differences in efficacy or harms were found between intramuscular and transdermal formulations. 1
• Intramuscular preparations are considerably more cost-effective. 1
• No head-to-head trials directly compared formulations, but observational data show no consistent safety differences. 1

Critical Safety Precautions for Transdermal Products

If transdermal products are used, strict adherence to transfer prevention is mandatory: 3

• Apply only to shoulders and upper arms that will be covered by a short-sleeve t-shirt—never to abdomen, genitals, chest, armpits, or knees. 3
• Wash hands immediately with soap and water after application. 3
• Cover application sites with clothing after gel dries. 3
• Wash application area thoroughly with soap and water before any skin-to-skin contact with others. 3
• Children and women must avoid contact with unwashed or unclothed application sites. 3
• Wait 2 hours before swimming or showering. 3
• Avoid fire, flames, or smoking until gel dries (alcohol-based products are flammable). 3

Secondary exposure to children has caused virilization (enlarged genitalia, premature pubic hair, aggressive behavior, advanced bone age), with some changes not fully reversible even after discontinuation. 3

Contraindications

Testosterone therapy is absolutely contraindicated in: 3

• Men with breast cancer or known/suspected prostate cancer
• Pregnant women or women who may become pregnant (risk of fetal virilization)
• Men with recent cardiovascular events (most trials excluded these patients)
• Men with elevated prostate-specific antigen levels

Monitoring Requirements

Patients on testosterone require periodic monitoring for serious complications: 2, 3

• Hemoglobin and hematocrit for polycythemia (occurs in 2.8-17.9% depending on formulation, up to 44% with injections). 2
• Prostate-specific antigen and digital rectal examination for prostate complications. 3
• Assessment for worsening benign prostatic hyperplasia symptoms (increased urination, weak stream, urgency). 3
• Cardiovascular monitoring, though trials were not powered to detect cardiovascular events. 1, 2

Evidence Limitations and Uncertainties

The evidence supporting testosterone therapy is weak, with critical gaps in long-term safety data: 1, 2

• Most trials lasted less than 1 year; long-term safety beyond 36 months is unknown. 1, 2
• No trials had adequate power to assess cardiovascular events, prostate cancer, thromboembolic disease, or mortality. 1
• While pooled analysis showed fewer deaths with testosterone (Peto OR 0.47), this evidence is too imprecise with low event rates to draw conclusions. 1
• Low-certainty evidence suggests a possible small increase in cardiovascular events (Peto OR 1.22). 2
• Trials typically excluded men at higher risk (recent cardiovascular disease, prostate cancer history), limiting generalizability. 1

Alternative Approaches

For men with bothersome symptoms despite contraindications or insufficient evidence for benefit, consider non-hormonal alternatives: 2

• PDE5 inhibitors for erectile dysfunction
• Exercise programs for fatigue and physical function
• Treatment of underlying conditions (diabetes, metabolic syndrome, obesity) that contribute to low testosterone

Common Pitfalls to Avoid

• Do not prescribe testosterone without documenting two fasting morning testosterone levels below the threshold (<275-320 ng/dL). 1
• Do not use testosterone for vague symptoms like "feeling tired" or "getting older" without confirmed hypogonadism from structural causes. 1
• Do not assume testosterone will improve overall quality of life, energy, or physical function—the evidence does not support these benefits. 1, 2
• Do not neglect counseling about transfer risks with transdermal products, especially to children and pregnant women. 3
• Do not prescribe oral testosterone undecanoate for age-related hypogonadism—the FDA specifically contraindicates this use due to blood pressure increases and lack of established efficacy. 1