What is the recommended medical management for low testosterone in healthy adults?

Medical Management of Low Testosterone in Healthy Adults

Primary Recommendation

Clinicians should NOT initiate testosterone treatment in men with age-related low testosterone to improve energy, vitality, physical function, or cognition. 1 The American College of Physicians provides a conditional recommendation against testosterone therapy for these nonspecific symptoms based on low-certainty evidence. 1

When to Consider Testosterone Treatment

Testosterone therapy should be considered ONLY in men with sexual dysfunction (erectile dysfunction or reduced libido) who have confirmed low testosterone levels. 1, 2

Specific Indications for Treatment:

• Sexual symptoms: Erectile dysfunction and decreased libido are the most reliable indicators warranting consideration of therapy 2
• Confirmed biochemical hypogonadism: Two separate morning testosterone measurements (8-10 AM) showing levels below normal range 2
• Known causes of hypogonadism: Primary hypogonadism (testicular failure) or hypogonadotropic hypogonadism (pituitary/hypothalamic dysfunction) 3

FDA-Approved Indications:

The FDA explicitly states that testosterone products are approved ONLY for conditions with deficiency or absence of endogenous testosterone due to known medical causes—NOT for age-related hypogonadism. 3 Safety and efficacy in "age-related hypogonadism" have not been established. 3

Critical Diagnostic Algorithm

Step 1: Symptom Assessment

• Prioritize sexual symptoms: Reduced libido, erectile dysfunction, decreased spontaneous/morning erections 2
• De-prioritize nonspecific symptoms: Fatigue, low energy, mood changes, cognitive complaints should NOT drive treatment decisions 1

Step 2: Laboratory Confirmation

• Measure morning total testosterone (8-10 AM) on two separate occasions 2
• Also measure free testosterone by equilibrium dialysis and SHBG, especially in obese men 2
• If subnormal, measure LH and FSH to distinguish primary from secondary hypogonadism 2

Step 3: Rule Out Contraindications

Absolute contraindications per FDA labeling: 3

• Breast cancer
• Known or suspected prostate cancer
• Pregnancy (for female partners—risk of virilization)

Evidence for Benefits and Harms

Sexual Function (The Primary Benefit):

• Moderate-certainty evidence shows testosterone improves sexual function with a small-to-moderate effect 1
• This is the ONLY outcome with meaningful clinical benefit supported by evidence 1

Outcomes WITHOUT Meaningful Benefit:

• Energy/vitality: Less-than-small improvement (SMD 0.17) 1
• Physical function: Minimal improvement in objective measures, no difference in self-reported function 1
• Cognitive function: No differences found 1
• Mood: Less-than-small improvement (SMD 0.19), but most men studied did not have baseline depression 1

Safety Profile:

• Cardiovascular events: Low-certainty evidence shows small increase to no difference (OR 1.22, CI 0.66-2.23) 1
• Serious adverse events: Moderate-certainty evidence shows no increased risk (OR 0.94) 1
• Mortality: Insufficient evidence to draw conclusions despite lower observed deaths in treatment groups 1
• Long-term safety data are lacking—most studies excluded men with recent cardiovascular disease 1

Treatment Formulations (If Initiated)

When treatment is appropriate, formulation choice depends on cost and patient preference: 1

• Injectable testosterone: Preferred by 53% of patients due to lower cost 1
• Topical gel: Preferred by 71% after trial use due to convenience and ease of use 1
• Annual cost difference: Transdermal formulations cost $2,135 vs. intramuscular $156 per year 1

Dosing for Testosterone Gel (Example):

• Starting dose: 40.5 mg daily applied to shoulders/upper arms 3
• Titrate based on pre-dose morning testosterone at 14 and 28 days 3
• Target range: 350-750 ng/dL 3

Critical Monitoring Requirements

Strict follow-up is mandatory if treatment is initiated: 4, 5

• Testosterone levels at 14 days, 28 days, then periodically 3
• Hematocrit monitoring (risk of erythrocytosis) 4
• PSA levels at set intervals 4
• Prostate examination before and during treatment 3
• Assessment for worsening urinary symptoms (BPH) 3

Common Pitfalls to Avoid

Do NOT test or treat based solely on: 1, 2

• Age alone in asymptomatic men 2
• Nonspecific symptoms like fatigue, low energy, or poor concentration without sexual symptoms 1
• Patient request for "optimization" or "anti-aging" purposes 3

Do NOT initiate treatment without: 2, 3

• Two separate morning testosterone measurements confirming low levels
• Presence of sexual symptoms (erectile dysfunction or reduced libido)
• Ruling out contraindications

Secondary exposure risk: Children and women must avoid contact with application sites—this is a boxed FDA warning due to virilization risk 3

The Bottom Line for Clinical Practice

The evidence supports a highly restrictive approach to testosterone therapy. Treatment should be reserved for men with both confirmed biochemical hypogonadism AND sexual dysfunction, not for the nonspecific symptoms that most commonly prompt patient requests. 1, 2 The American College of Physicians' guideline, endorsed by the American Academy of Family Physicians, explicitly recommends against treatment for energy, vitality, physical function, or cognition. 1 This conservative stance prioritizes patient safety given the lack of long-term safety data and minimal benefits for non-sexual outcomes. 1