What are the symptoms and treatment options for low testosterone in adult males?

Symptoms of Low Testosterone in Adult Males

Sexual Symptoms (Most Specific)

Reduced libido (decreased sexual desire) is the most reliable and specific symptom of hypogonadism in adult males, followed closely by erectile dysfunction and decreased spontaneous or morning erections. 1

• Decreased libido is the most specific symptom warranting testosterone testing and is considered a primary indicator of hormonal dysfunction 1
• Erectile dysfunction, particularly when PDE5 inhibitor therapy (like sildenafil) has failed, strongly suggests underlying hypogonadism 1, 2
• Reduced spontaneous or morning erections are considered "more specific" for hypogonadism compared to other symptom categories 1
• Approximately 36% of men seeking consultation for sexual dysfunction have confirmed hypogonadism 2

Physical Symptoms

• Decreased vigorous activity and reduced physical function are common physical manifestations 1
• Difficulty walking more than 1 km and decreased bending ability are specific physical findings associated with hypogonadism 1
• Loss of body and facial hair occurs with testosterone deficiency 1
• Osteoporotic changes (decreased bone mineral density) develop as a consequence of prolonged hypogonadism 1
• Decreased muscle mass and increased body fat result from testosterone deficiency 3

Psychological Symptoms (Less Specific)

• Low mood or depression is commonly reported but less specific for hypogonadism 1
• Decreased motivation and fatigue are associated symptoms but can have multiple causes 1
• Reduced sense of vitality and psychological energy may occur 2

Important caveat: The American College of Physicians specifically recommends against initiating testosterone treatment to improve energy, vitality, physical function, or cognition alone, as evidence shows little to no benefit for these outcomes. 1, 2

Treatment Options

Diagnostic Confirmation Required First

Before any treatment, confirm the diagnosis with morning total testosterone measured between 8-10 AM on at least two separate occasions, with levels below 300 ng/dL indicating hypogonadism. 1, 2

• Measure free testosterone by equilibrium dialysis and sex hormone-binding globulin (SHBG), especially in men with obesity 1, 2
• If testosterone is subnormal, measure serum LH and FSH to distinguish primary from secondary hypogonadism 1, 2

First-Line Treatment: Transdermal Testosterone Gel

Transdermal testosterone gel is the preferred first-line formulation, starting at 40.5 mg daily applied to shoulders and upper arms. 2, 4

• Provides more stable day-to-day testosterone levels compared to injections 2
• Target mid-normal testosterone levels (500-600 ng/dL) during treatment 2
• Annual cost approximately $2,135 2
• Check testosterone levels at 2-3 months after initiation, then every 6-12 months once stable 2

Alternative: Intramuscular Testosterone Injections

For cost-conscious patients, intramuscular testosterone cypionate or enanthate 100-200 mg every 2 weeks is more economical at $156 annually. 2

• Peak levels occur 2-5 days after injection, returning to baseline by days 10-14 2
• Measure testosterone levels midway between injections (days 5-7) 2
• Higher risk of erythrocytosis compared to transdermal preparations 2

Expected Treatment Outcomes

Testosterone therapy produces small but significant improvements in sexual function and libido (standardized mean difference 0.35), but little to no effect on physical functioning, energy, vitality, or cognition. 2

• Sexual function and libido: Small but significant improvements 2
• Quality of life: Modest improvements, primarily in sexual function domains 2
• Physical functioning: Little to no effect 2
• Energy and vitality: Minimal improvements (SMD 0.17) 2
• Depressive symptoms: Less-than-small improvements (SMD -0.19) 2
• Cognition: No meaningful benefit 2

Absolute Contraindications to Testosterone Therapy

Never initiate testosterone in men with: 2, 4

• Active desire for fertility preservation (use gonadotropin therapy instead) 2
• Active or treated male breast cancer 2
• Prostate cancer (though evidence is evolving) 2
• Hematocrit >54% 2
• Untreated severe obstructive sleep apnea 2

Critical Monitoring Requirements

• Hematocrit: Monitor periodically, withhold treatment if >54%, consider phlebotomy in high-risk cases 2
• PSA levels: Monitor 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 2
• Clinical response: Reevaluate at 12 months and discontinue if no improvement in sexual function 2

Special Consideration: Fertility Preservation

For men with secondary hypogonadism who desire fertility, gonadotropin therapy (recombinant hCG plus FSH) is mandatory—testosterone is absolutely contraindicated as it causes azoospermia. 2

Lifestyle Modifications

For men with obesity-associated secondary hypogonadism, attempt weight loss through low-calorie diets and regular exercise before initiating testosterone, as this can improve testosterone levels without medication. 2