What is the recommended protocol for testosterone injection therapy in treating hypogonadism?

From the Guidelines

The recommended protocol for testosterone injection therapy in treating hypogonadism typically involves testosterone cypionate or enanthate injections administered intramuscularly at doses of 50-100 mg weekly or 100-200 mg every two weeks, as supported by recent evidence from the American College of Physicians 1.

Key Considerations

• Treatment should begin after confirming hypogonadism through morning total testosterone levels below 300 ng/dL on two separate occasions, along with symptoms such as decreased libido, fatigue, and reduced muscle mass.
• Injections are typically administered into the gluteal muscle or thigh.
• Patients should have baseline measurements of hematocrit, PSA (in men over 40), and lipid profiles before starting therapy, with follow-up monitoring at 3-6 months and then annually.
• Testosterone levels should be checked midway between injections, aiming for mid-normal range (400-700 ng/dL).
• Some patients may benefit from more frequent, smaller doses (e.g., twice weekly) to maintain steadier hormone levels and reduce side effects like mood swings.

Important Outcomes

• Treatment is typically lifelong for primary hypogonadism, while secondary hypogonadism may sometimes be reversible.
• This approach effectively restores physiologic testosterone levels, improving energy, libido, muscle mass, and bone density while minimizing potential side effects like erythrocytosis, acne, and potential cardiovascular risks, as noted in studies 1.

Monitoring and Safety

• Long-term efficacy and safety are unknown, and patients should be closely monitored for potential adverse effects.
• The FDA has required companies that manufacture testosterone products to conduct a controlled clinical trial to evaluate the effects of testosterone therapy on cardiovascular outcomes, as mentioned in 1.

From the FDA Drug Label

DOSAGE AND ADMINISTRATION Prior to initiating Aveed, confirm the diagnosis of hypogonadism by ensuring that serum testosterone has been measured in the morning on at least two separate days and that these concentrations are below the normal range. For intramuscular use only. Three (3) mL (750 mg) is to be injected intramuscularly at initiation, at 4 weeks, and every 10 weeks thereafter.

The recommended dose of AVEED is 3 mL (750 mg) injected intramuscularly, followed by 3 mL (750 mg) injected after 4 weeks, then 3 mL (750 mg) injected every 10 weeks thereafter.

The recommended protocol for testosterone injection therapy in treating hypogonadism is:

• Initiation: 3 mL (750 mg) intramuscularly
• Follow-up: 3 mL (750 mg) at 4 weeks, and every 10 weeks thereafter
• Administration: Inject deeply into the gluteal muscle, following the usual precautions for intramuscular administration of oily solutions
• Observation: Observe patients in the healthcare setting for 30 minutes after each injection to monitor for serious POME reactions or anaphylaxis 2, 2, 2.

From the Research

Testosterone Injection Therapy for Hypogonadism

• The recommended protocol for testosterone injection therapy in treating hypogonadism involves weekly-to-biweekly injections of testosterone cypionate or testosterone enanthate, which are widely used due to their economical and generally well-tolerated nature 3.
• Another option is the intramuscular injection of testosterone undecanoate, which can be administered quarterly, providing an attractive new therapy for hypogonadism 3, 4.
• The treatment should be initiated only after two morning total serum testosterone measurements show decreased levels, and all patients should be counseled on the potential risks and benefits before starting therapy 5.
• The benefits of androgen replacement therapy in hypogonadal men include improved sexual function, an enhanced sense of well-being, increased lean body mass, decreased body fat, and increased bone density 3.
• However, testosterone therapy may also carry potential risks, including the possibility of stimulating the growth of an occult prostate cancer, rising prostate-specific antigen levels, worsening lower urinary tract symptoms, polycythemia, and increased risk of venous thromboembolism 3, 5, 6.

Monitoring and Follow-up

• To confirm an adequate replacement dosage, assessment of clinical responses and measurement of serum testosterone levels generally suffice 3.
• For selected men, serial measurement of bone mineral density during androgen therapy might be helpful to confirm end-organ effects 3.
• For men aged >50 years, measurement of hematocrit for detection of polycythemia and a digital rectal examination with a serum prostate-specific antigen level measurement for prostate cancer screening during the first few months of androgen therapy are recommended 3.
• A hematocrit should be obtained yearly or after changes in therapy, and annual prostate cancer screening can be offered to the patient after a discussion of its risks and benefits 3.

Comparison of Testosterone Therapies

• A study comparing intramuscular testosterone cypionate (IM-TC) and subcutaneous testosterone enanthate autoinjector (SCTE-AI) found that both provide a significant increase in total testosterone levels, but SCTE-AI is associated with lower levels of post-therapy estradiol and hematocrit compared to IM-TC 7.
• Testosterone undecanoate injected at extended intervals of 12 weeks has been shown to be an effective and safe treatment option for male hypogonadism, with minimal changes in body weight, hemoglobin, serum lipids, prostate-specific antigen, and prostate volume during treatment 4.