Treatment for Low Testosterone (Hypogonadism)
Testosterone replacement therapy (TRT) is the first-line treatment for men with confirmed hypogonadism, with transdermal formulations generally preferred over intramuscular injections due to more stable testosterone levels and lower risk of side effects. 1
Diagnosis Confirmation
- Diagnosis requires both persistent specific symptoms and confirmed testosterone deficiency through biochemical testing 1
- Morning serum total testosterone measurements should be repeated to confirm low levels (drawn between 8 AM and 10 AM) 1
- Free testosterone and sex hormone-binding globulin levels should be measured, especially in men with obesity 1
- Serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) should be measured to distinguish primary (testicular) from secondary (pituitary-hypothalamic) hypogonadism 1
Treatment Options
Transdermal Testosterone
- Provides more stable day-to-day testosterone levels 1
- Lower risk of erythrocytosis (3-18%) compared to injections (up to 44%) 2
- More expensive option ($2,135.32 annually) 3
- Some patients prefer topical gel over injections for convenience, ease of use, and non-staining of clothes 3
Intramuscular Testosterone
- Administered every 2-3 weeks (cypionate or enanthate) 1
- More economical option ($156.24 annually) 3
- Peak serum levels occur 2-5 days after injection, with return to baseline usually observed 10-14 days after injection 1
- Some patients prefer injectable testosterone over gel-based preparations due to lower cost 3
- Higher risk of erythrocytosis compared to transdermal preparations 1
FDA-Approved Indications
- TRT is indicated for primary hypogonadism (testicular failure) and hypogonadotropic hypogonadism (pituitary-hypothalamic dysfunction) 4
- Safety and efficacy in "age-related hypogonadism" have not been established 4
Monitoring Treatment
- Testosterone levels should be tested 2-3 months after treatment initiation and/or after any dose change 1
- For patients receiving testosterone injections, levels should be measured midway between injections, targeting a mid-normal value (500-600 ng/dL) 1
- Once stable levels are confirmed, monitoring every 6-12 months is typically sufficient 1
- Monitor for erythrocytosis, fluid retention, benign prostatic hyperplasia, sleep apnea, gynecomastia, acne, and testicular atrophy 1
Expected Benefits
- Improved sexual function and libido 1
- Possible improvements in fasting plasma glucose, insulin resistance, and lipid profile 1
- Small improvements in vitality and fatigue 3
- Modest improvements in depressive symptoms 3
Special Considerations
Fertility Concerns
- TRT may compromise fertility by suppressing the hypothalamic-pituitary-gonadal axis 1, 5
- For men wishing to preserve fertility, alternative treatments include:
Weight Management
- Weight loss through low-calorie diets can improve testosterone levels in men with obesity-associated secondary hypogonadism 1
- Regular physical activity and exercise should be encouraged 1
Treatment Algorithm
- Confirm diagnosis with repeated morning testosterone measurements and appropriate symptom assessment 1
- Determine if fertility preservation is needed:
- Select TRT formulation based on:
- Monitor treatment efficacy and safety as recommended 1
- If no improvement in symptoms after 12 months, consider discontinuing treatment 1
Cautions and Contraindications
- TRT is not recommended for men with "age-related hypogonadism" without confirmed low testosterone levels 4
- Use caution in men with prostate cancer, breast cancer, uncontrolled congestive heart failure, severe lower urinary tract symptoms, or erythrocytosis 7
- The European Association of Urology specifically recommends against using testosterone therapy in eugonadal individuals 1