What is the recommended treatment for hypogonadism (low testosterone) in men using testosterone injections?

Testosterone Injection Treatment for Male Hypogonadism

For men with confirmed hypogonadism, testosterone replacement therapy via intramuscular injections is an effective treatment option, particularly for those who prefer less frequent administration or have cost concerns, though transdermal preparations may be preferred for most patients due to more stable testosterone levels.

Diagnosis of Hypogonadism

• 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 due to variability in assays 1
• Assessment should include morning total testosterone concentration drawn between 8 AM and 10 AM, as well as free testosterone level by equilibrium dialysis and sex hormone-binding globulin level, especially in men with obesity 2
• If testosterone levels are subnormal, they should be repeated, and serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) concentrations should be measured to distinguish primary (testicular) from secondary (pituitary-hypothalamic) hypogonadism 2
• If testosterone levels are low with concomitantly low LH/FSH, further evaluation to identify the etiology of hypothalamic and/or pituitary dysfunction may include measurements of serum prolactin and iron saturation, pituitary function testing, and MRI of the sella turcica 2

Symptoms and Signs of Hypogonadism

• Diminished libido and sense of vitality 2
• Erectile dysfunction 2
• Reduced muscle mass and bone density 2
• Depression and anemia 2
• Increased fatigue 2
• Impaired cognition 2
• Decreased energy, muscle mass, and body hair 2
• Hot flashes, gynecomastia, and infertility 2

Testosterone Injection Therapy

Indications

• FDA-approved for replacement therapy in males with conditions associated with deficiency or absence of endogenous testosterone 3
• Primary hypogonadism (congenital or acquired) - testicular failure due to cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome, or orchidectomy 3
• Hypogonadotropic hypogonadism (congenital or acquired) - idiopathic gonadotropin or LHRH deficiency, or pituitary-hypothalamic injury from tumors, trauma, or radiation 3

Administration and Pharmacokinetics

• Intramuscular testosterone injections (cypionate or enanthate) are administered every 2-3 weeks 2
• Peak serum levels occur 2-5 days after injection, with return to baseline usually observed 10-14 days after injection 2
• For patients receiving testosterone injections, levels should be measured midway between injections, targeting a mid-normal value (500-600 ng/dL) 2

Advantages of Injections

• Low cost compared to other formulations (annual cost in 2016 per Medicare beneficiary: $156.24 for intramuscular vs. $2135.32 for transdermal) 2
• Avoids daily administration 2
• Advantageous in patients with reduced personal disease-management skills or resources 2
• High peak serum levels of testosterone 2

Disadvantages of Injections

• Pain of injection 2
• Need for frequent medical visits for administration 2
• "Roller coaster" effect with alternating periods of symptomatic benefit and return to baseline symptoms, corresponding to fluctuations in serum testosterone levels 2
• Higher risk of erythrocytosis (up to 44% with injection vs. 3-18% with transdermal administration) 2

Monitoring Recommendations

• Testosterone levels should be tested 2-3 months after treatment initiation and/or after any dose change 2
• Once stable levels are confirmed on a given dose, monitoring every 6-12 months is typically sufficient 2
• For men aged >50 years, measurement of hematocrit for detection of polycythemia and a digital rectal examination with serum PSA measurement for prostate cancer screening during the first few months of therapy 4
• Subsequently, hematocrit should be obtained yearly or after changes in therapy, and annual prostate cancer screening can be offered 4

Potential Benefits of Testosterone Therapy

• Improved sexual function and libido 2, 5
• Enhanced sense of well-being and energy 5
• Increased lean body mass and decreased body fat 4, 5
• Increased bone density 4
• Improvements in fasting plasma glucose, insulin resistance, triglyceride levels, and HDL cholesterol 2
• Alleviation of depressed mood 5

Potential Risks and Side Effects

• Erythrocytosis (higher risk with injections than transdermal preparations) 2
• Fluid retention (rarely of clinical significance) 2
• Benign prostatic hyperplasia (rarely of clinical significance) 2
• Prostate cancer (controversial; unknown level of risk; requires long-term monitoring) 2
• Sleep apnea (infrequent) 2
• Gynecomastia (rare, usually reversible) 2
• Acne or oily skin (infrequent) 2
• Testicular atrophy or infertility (common, especially in young men; usually reversible with cessation of treatment) 2

Comparative Effectiveness with Other Formulations

• Transdermal testosterone preparations (gel, patch) are often favored over intramuscular injections due to the relative stability of testosterone levels from day-to-day 2
• Transdermal preparations are recommended for most hypogonadal men because they usually produce normal serum testosterone concentrations and patients typically find them more convenient 2
• Patient preferences vary - in one study, 53% of patients chose injectable testosterone over gel-based pellet regimens, mostly because of lower cost 2, while another study found 71% preferred topical gel over injection or patch for reasons of convenience, ease of use, and non-staining of clothes 2