What are the guidelines for using artificial testosterone shots, specifically testosterone replacement therapy (TRT), for treating hypogonadism?

Testosterone Replacement Therapy Guidelines

Testosterone replacement therapy should only be prescribed to men with confirmed hypogonadism (both persistent symptoms AND laboratory-confirmed low morning testosterone levels between 8-10 AM on at least two separate occasions), specifically when the cause is related to testicular, pituitary, or hypothalamic dysfunction—not for aging alone or to enhance performance in eugonadal men. 1, 2

Diagnostic Requirements

Before initiating TRT, you must confirm:

• Morning total testosterone drawn between 8-10 AM on two separate occasions showing persistently low levels 1
• Presence of specific hypogonadal symptoms (decreased libido, erectile dysfunction, depressed mood, loss of muscle/bone mass) 1, 2
• LH and FSH measurements to distinguish secondary (low/normal LH/FSH) from primary hypogonadism (elevated LH/FSH) 1
• Free testosterone by equilibrium dialysis and SHBG, particularly in obese patients where total testosterone may be misleading 1
• Assessment for reversible causes: pituitary disorders, medications affecting the HPG axis, obesity, and metabolic disorders 1

Critical pitfall: Do not test testosterone during acute illness, as levels may be falsely low 1

FDA-Approved Indications

The FDA label explicitly approves testosterone enanthate for: 2

• Primary hypogonadism (testicular failure from cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome, orchidectomy)
• Hypogonadotropic hypogonadism (gonadotropin or LHRH deficiency, pituitary-hypothalamic injury from tumors, trauma, or radiation)
• Carefully selected males with clearly delayed puberty
• Women with metastatic mammary cancer (secondary use)

The FDA has NOT established safety and efficacy for age-related hypogonadism 2

Absolute Contraindications

Do not prescribe TRT in men with: 3, 1

• Active or treated male breast cancer
• Desire for fertility in the near future (TRT suppresses spermatogenesis) 3, 1, 4

Relative Contraindications Requiring Caution

Exercise extreme caution and individual risk assessment in: 3, 1

• Cardiovascular disease: The FDA issued a 2015 Safety Announcement warning of possible increased risk of heart attack and stroke, though level 1 trials showed conflicting results 3
• Prostate cancer history: Particularly in locally advanced or metastatic disease; post-radical prostatectomy with favorable pathology may be considered with shared decision-making 3
• Severe lower urinary tract symptoms: Though recent trials suggest moderate LUTS may not worsen with TRT 3
• Uncontrolled/severe congestive heart failure 3
• Untreated obstructive sleep apnea: Recent evidence suggests this may not be an absolute contraindication 3

Treatment Selection Algorithm

First-line approach: 1

• TRT is recommended as first-line treatment for symptomatic secondary hypogonadism when fertility is not an immediate concern
• For mild erectile dysfunction: TRT alone 1
• For severe erectile dysfunction: Consider combination of TRT with PDE5 inhibitors 1

Formulation selection based on patient factors: 1

• Transdermal gel/patch: Provides stable levels but variable absorption; risk of transfer to others 1
• Intramuscular injections: Less frequent administration but fluctuating levels 1
• Implantable pellets: Long-term treatment requiring procedural implantation 1

Special Population: Obesity and Metabolic Syndrome

For obese men with functional hypogonadism: 1

• Weight loss through diet and physical activity can reverse obesity-associated secondary hypogonadism
• Lifestyle modifications alone yield modest testosterone increases
• Recommended approach: Combine lifestyle changes with TRT for better outcomes in symptomatic patients 1
• TRT shows beneficial effects on insulin sensitivity and biometric parameters in metabolic syndrome, though results are conflicting 3

Monitoring Protocol

Initial monitoring (first 2-3 months): 1

• Clinical response assessment at 3 months
• Testosterone levels at 2-3 months after initiation
• Hematocrit monitoring; consider phlebotomy if >54%
• PSA monitoring per shared decision-making approach

Ongoing surveillance: 3, 1

• PSA testing using shared decision-making in accordance with AUA Early Detection of Prostate Cancer Guidelines
• Patients with prostate cancer history should have PSA monitored on the same schedule as men without testosterone deficiency, though clinicians may increase testing frequency 3

Fertility Preservation Considerations

Critical counseling point: 3, 4

• The long-term impact of exogenous testosterone on spermatogenesis must be discussed with all men interested in future fertility
• For men planning future reproduction, testosterone cessation should occur well in advance of conception attempts
• Recovery time to restore sperm in ejaculate is highly variable 3, 4
• Spontaneous recovery of spermatogenesis may occur after TRT cessation, but some patients may not recover or tolerate waiting 4

Alternative for fertility preservation: 5

• Gonadotropins are the preferred alternative when fertility is desired in the near future, though they require frequent injections
• Clomiphene citrate may increase testosterone levels but lacks sufficient data on efficacy for hypogonadal symptoms and should not be used routinely 5

What NOT to Do

The European Urology guidelines explicitly recommend against: 1

• Using TRT in eugonadal men
• Using TRT to reduce weight or enhance cardiometabolic status as a primary goal
• Using TRT to improve cognition, vitality, or physical strength in aging men without documented hypogonadism
• Overlooking fertility concerns when initiating TRT in men of reproductive age

FDA warning: TRT should not be used for hypogonadism due to aging alone 3

Cardiovascular Risk Counseling

Patients must be informed: 3

• The FDA found a "possible" increased risk of cardiovascular events with TRT based on retrospective studies
• Level 1 randomized trials showed conflicting results—some showed increased CV risk, others showed no difference or even reduced risk
• All patients starting or currently prescribed TRT should be advised of these possible cardiovascular risks