Good Practice in Testosterone Replacement Therapy (TRT): Recent Updates

Introduction

Testosterone replacement therapy (TRT) has received renewed public attention following announcements regarding testosterone screening among U.S. military personnel. In response, the Endocrine Society highlighted several key principles of evidence-based testosterone therapy that apply to all men being evaluated for possible testosterone deficiency.

These recommendations reinforce an important message: good testosterone treatment begins with the correct diagnosis—not simply a low laboratory value or nonspecific symptoms.

1. Make the Diagnosis Correctly

Male hypogonadism is a clinical diagnosis that requires:

• Symptoms and/or signs consistent with testosterone deficiency;
• Consistently low morning testosterone levels on at least two separate fasting blood tests;
• Reliable laboratory testing.

Many common complaints—including fatigue, low energy, poor concentration, depressed mood, decreased motivation, and reduced libido—may result from numerous other conditions such as:

• Obesity
• Obstructive sleep apnea
• Chronic stress
• Depression
• Chronic illness
• Glucocorticoid therapy
• Opioid medications
• Thyroid disease

For men with obesity (BMI >27 kg/m²) and no other established cause of hypogonadism, weight loss remains first-line therapy, as testosterone levels often improve with reduction in body fat.

2. TRT Has Proven Benefits—but Also Potential Risks

For men with confirmed hypogonadism caused by disorders of the testes, pituitary gland, or hypothalamus, testosterone therapy has been shown to improve:

• Sexual function
• Libido
• Mood
• Lean muscle mass
• Muscle strength
• Bone mineral density
• Quality of life

The large TRAVERSE trial involving more than 5,200 men found no increase in major cardiovascular events (heart attack or stroke) during approximately 1–4 years of follow-up.

However, investigators also observed:

• Increased relative risk of pulmonary embolism;
• Higher fracture rates.

Long-term safety—including the potential relationship with prostate cancer—continues to be studied.

For these reasons, appropriate patient selection and regular monitoring remain essential throughout treatment.

3. Laboratory Quality Matters

One of the most overlooked aspects of testosterone evaluation is laboratory accuracy.

Different laboratories may report substantially different testosterone values from the same blood sample because of differences in assay methodology.

The Endocrine Society recommends using standardized testosterone assays whenever possible, including laboratories participating in the CDC Hormone Standardization (HoST) Program.

Poor-quality laboratory testing increases the risk of:

• Diagnosing hypogonadism when it is not present;
• Missing genuine testosterone deficiency;
• Making inappropriate treatment decisions.

Shared Decision-Making

Testosterone therapy should never be viewed as a universal solution for fatigue or aging.

Instead, treatment decisions should be individualized after discussing:

• Expected benefits;
• Potential risks;
• Fertility considerations;
• Alternative treatments;
• Appropriate monitoring.

Shared decision-making remains a cornerstone of high-quality endocrine care.

Key Takeaways

• Testosterone deficiency requires both symptoms and consistently low testosterone levels.
• Many symptoms commonly attributed to "low testosterone" have other medical causes.
• Weight loss is first-line therapy for many men with obesity-related low testosterone.
• TRT improves sexual function, muscle mass, bone health, and quality of life in appropriately selected patients.
• Long-term safety continues to be studied, making regular follow-up important.
• Accurate laboratory testing is essential before making treatment decisions.

References

• Endocrine Society. Statement on Testosterone Replacement Therapy (2026).
• Endocrine Society Clinical Practice Guideline: Testosterone Therapy in Men with Hypogonadism.
• TRAVERSE Trial (2023).