What are the symptoms, causes, and treatments of andropause, including lifestyle modifications and Testosterone Replacement Therapy (TRT) with methods such as pellets, injections, and creams?

Andropause: Symptoms, Causes, and Treatment Options

Testosterone replacement therapy (TRT) is recommended for men with confirmed low testosterone levels who exhibit symptoms of andropause, with treatment selection based on patient preference, comorbidities, and treatment goals. 1, 2

Symptoms of Andropause

Andropause, also known as late-onset hypogonadism or testosterone deficiency syndrome, presents with various symptoms:

Sexual Symptoms

• Decreased libido/sexual desire
• Erectile dysfunction
• Reduced morning erections
• Decreased testicle size

Physical Symptoms

• Fatigue and reduced energy levels
• Decreased muscle mass and strength
• Reduced bone density (osteoporosis risk)
• Increased body fat
• Gynecomastia (breast enlargement)
• Thinning of body hair
• Anemia

Psychological Symptoms

• Depressed mood
• Anxiety and irritability
• Reduced motivation
• Impaired cognition and memory
• Sleep disturbances
• Decreased sense of well-being 1

Causes of Andropause

Andropause is primarily characterized by:

• Age-related decline in testosterone (approximately 1% per year after age 40)
• Approximately 20% of men aged 60-80 years have testosterone levels below normal range
• Primary gonadal insufficiency (testicular failure)
• Secondary causes (hypothalamic-pituitary dysfunction)
• Metabolic factors (obesity, diabetes)

Diabetes significantly impacts testosterone levels, with research showing earlier onset of andropause symptoms in diabetic men compared to non-diabetic men 3.

Diagnosis

Diagnosis requires both:

1. Clinical symptoms of hypogonadism
2. Biochemical evidence of low testosterone

Laboratory evaluation should include:

• Morning total testosterone levels (ideally between 8-10 AM)
• Free testosterone
• Luteinizing hormone (LH) and follicle-stimulating hormone (FSH)
• Complete blood count
• Prostate-specific antigen (PSA) in men over 40 1

Treatment Options

Lifestyle Modifications

• Weight loss for overweight/obese men
• Regular physical activity and exercise
• Adequate sleep (7-8 hours)
• Stress reduction techniques
• Healthy diet (Mediterranean diet recommended)
• Moderate alcohol consumption
• Smoking cessation 1, 2

These lifestyle changes can increase testosterone levels by 1-2 nmol/L and improve symptoms, particularly in men with metabolic disorders or obesity 1.

Testosterone Replacement Therapy (TRT)

TRT should be considered when:

• Total testosterone level is below 350 ng/dL with symptoms
• Levels between 231-346 ng/dL may warrant a 4-6 month trial if symptomatic
• Levels below 230 ng/dL usually benefit from treatment 1

TRT Formulations:

1. Injectable testosterone

   • Testosterone cypionate/enanthate: 50-100 mg weekly
   • Advantages: Low cost, high peak levels
   • Disadvantages: "Roller coaster" effect with fluctuating levels, pain at injection site, frequent medical visits 1, 2

2. Transdermal formulations

   • Testosterone gel (1%): 50-100 mg daily
   • Advantages: Stable testosterone levels, lower risk of erythrocytosis
   • Disadvantages: Risk of transfer to women/children, skin irritation (5%) 1, 2

3. Testosterone pellets

   • Implanted subcutaneously
   • Advantages: Long-lasting (3-6 months), stable levels
   • Disadvantages: Requires minor procedure, risk of extrusion, infection 1

Benefits of TRT

Studies show TRT can improve:

• Sexual function (libido and erectile function)
• Energy levels and vitality
• Muscle mass and strength
• Bone mineral density
• Mood and sense of well-being
• Quality of life 4, 2

Contraindications to TRT

Absolute contraindications:

• Active prostate or breast cancer
• Hematocrit >50%
• Severe untreated sleep apnea
• Uncontrolled heart failure
• Recent cardiovascular events (within 3-6 months) 2

Monitoring During TRT

Regular monitoring is essential:

• Total testosterone: Target 450-600 ng/dL (check at 3 months, then annually)
• Hematocrit: Discontinue if >54%
• PSA: Biopsy if >4.0 ng/mL or increases >1.0 ng/mL in any year
• Digital rectal examination: Annually 1, 2

Special Considerations

Sleep Apnea

TRT can be safely administered in patients with obstructive sleep apnea who are adequately treated with CPAP. Combined CPAP and testosterone therapy shows better outcomes than CPAP alone 2.

Cardiovascular Risk

Current evidence suggests TRT has a neutral or possibly beneficial effect on cardiovascular health, contrary to earlier beliefs 1.

Prostate Health

While theoretical concerns exist about TRT stimulating prostate cancer, studies show only mild increases in PSA with treatment. Regular monitoring is still essential 1, 5.

Common Pitfalls to Avoid

1. Treating men with normal testosterone levels
2. Failing to identify secondary causes of hypogonadism
3. Not monitoring hematocrit (risk of polycythemia)
4. Overlooking prostate health monitoring
5. Using custom-compounded bioidentical hormones without evidence of superiority
6. Not discussing potential fertility impacts with younger patients

TRT has shown significant benefits for men with confirmed low testosterone and andropause symptoms, but treatment should be approached with careful consideration of individual risk factors and regular monitoring.