What is the primary treatment approach for patients with hypogonadism (low testosterone)?

Treatment for Low Testosterone (Hypogonadism)

Testosterone replacement therapy (TRT) is the primary treatment for confirmed male hypogonadism with both persistent specific symptoms and biochemically confirmed testosterone deficiency. 1

Diagnosis and Confirmation

• Diagnosis requires both persistent symptoms (decreased libido, fatigue, erectile dysfunction) and confirmed low testosterone levels through biochemical testing 1
• Morning total testosterone concentration should be drawn between 8 AM and 10 AM and repeated to confirm low levels due to variability in assays 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) concentrations should be measured to distinguish primary (testicular) from secondary (pituitary-hypothalamic) hypogonadism 1

Treatment Options for Male Hypogonadism

First-Line Treatment: Testosterone Replacement Therapy

• TRT is indicated for replacement therapy in conditions associated with deficiency or absence of endogenous testosterone 2
• Treatment options include:

1. Injectable Testosterone

   • Intramuscular testosterone injections (cypionate or enanthate) administered every 2-3 weeks 1
   • More economical option compared to topical formulations 3
   • Peak serum levels occur 2-5 days after injection, with return to baseline usually observed 10-14 days after injection 1
   • Higher risk of erythrocytosis compared to transdermal preparations 1

2. Transdermal Formulations

   • Often favored over intramuscular injections due to more stable day-to-day testosterone levels 1
   • Lower risk of polycythemia (3-18%) compared to injections (up to 44%) 3
   • More expensive than injectable options 3

3. Other Formulations

   • All approved testosterone replacement methods can restore normal serum testosterone concentrations when used according to recommendations 4
   • Selection depends on patient preference with physician guidance 4

Alternative Approaches (When Fertility Preservation is Important)

• TRT induces reversible suppression of spermatogenesis 4
• Alternative options to preserve fertility include:
  • Human chorionic gonadotropin (hCG) 4, 5
  • Selective estrogen receptor modulators 4, 6
  • Aromatase inhibitors 4, 6
  • Gonadotropin therapy (combination of FSH and hCG) for hypogonadotropic hypogonadism 5

Monitoring and Follow-up

• 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 on a given dose, monitoring every 6-12 months is typically sufficient 1
• Monitor for potential side effects:
  • Erythrocytosis (higher risk with injections) 1
  • Fluid retention 1
  • Benign prostatic hyperplasia 1
  • Sleep apnea 1
  • Gynecomastia 1, 5
  • Testicular atrophy or infertility 1

Important Cautions and Considerations

• FDA specifically contraindicates the use of oral testosterone formulations for "age-related hypogonadism" not associated with structural or genetic etiologies 3
• The European Association of Urology specifically recommends against using testosterone therapy in eugonadal individuals 1
• TRT may compromise fertility in men by suppressing the hypothalamic-pituitary-gonadal axis 1
• Weight loss through low-calorie diets can improve testosterone levels in men with obesity-associated secondary hypogonadism 1
• Hepatotoxic androgens must be avoided 4

Treatment for Female Hypogonadism

• For premenopausal women with hypogonadism, estrogen replacement with progesterone is recommended as first-line therapy 1, 7
• Testosterone enanthate may be used in specific cases of metastatic mammary cancer in women who are 1-5 years postmenopausal 2