What are the differences in testosterone levels, including free testosterone, between subcutaneous and intramuscular administration of testosterone cypionate in patients with hypogonadism?

From the Guidelines

Testosterone cypionate administration via subcutaneous (SC) or intramuscular (IM) injection generally results in similar testosterone levels for treating hypogonadism, with SC being slightly preferred.

Recommendation

Use subcutaneous administration of testosterone cypionate, typically 50-100 mg weekly or 100-200 mg every two weeks. SC injections are easier to self-administer, less painful, and may lead to more stable testosterone levels compared to IM injections. They also have a lower risk of injection site complications.

Key Points

• Both methods effectively raise total and free testosterone levels in hypogonadal men.
• Any differences in peak levels or time to peak are usually not clinically significant.
• The similar effectiveness is due to the slow release of testosterone from the cypionate ester, which occurs comparably in both muscle and fat tissue.
• The large molecular size of testosterone cypionate allows for sustained release regardless of injection site.

Implementation

To implement subcutaneous testosterone cypionate administration:

1. Use a 25-27 gauge, 5/8 inch needle for SC injection.
2. Inject into abdominal fat, rotating sites.
3. Monitor testosterone levels, hematocrit, and PSA regularly.
4. Adjust dose based on symptoms and lab results. According to the most recent evidence from 1 and 1, there is no significant difference in reported outcomes by testosterone formulation (intramuscular vs. transdermal), but patient characteristics, testosterone levels, and outcome reporting varied in studies of intramuscular versus transdermal formulations. However, the evidence from 1 and 1 suggests that transdermal testosterone preparations are generally preferred due to their relative stability of testosterone levels from day-to-day and the ability to avoid the discomfort of intramuscular injections. Nevertheless, the method of testosterone replacement should be individualized for each patient.

From the Research

Testosterone Levels and Administration Methods

The differences in testosterone levels, including free testosterone, between subcutaneous and intramuscular administration of testosterone cypionate in patients with hypogonadism are as follows:

• There is no direct comparison of subcutaneous and intramuscular administration of testosterone cypionate in the provided studies 2, 3, 4, 5, 6.
• However, a study comparing intramuscular testosterone cypionate (IM-TC) and subcutaneous testosterone enanthate autoinjector (SCTE-AI) found that both treatments provided a significant increase in trough total testosterone (TT) levels, but SCTE-AI was associated with lower post-therapy estradiol (E2) and hematocrit (HCT) levels 3.
• Another study discussed the various methods of testosterone replacement therapy, including intramuscular injections, transdermal therapies, and subcutaneous injections, but did not directly compare the effects of subcutaneous and intramuscular administration of testosterone cypionate on testosterone levels 4.
• The use of different routes of administration, such as transdermal therapies, has been shown to be effective in delivering physiologic levels of testosterone and may be associated with fewer side effects compared to intramuscular injections 5, 6.

Key Findings

• Intramuscular testosterone cypionate and subcutaneous testosterone enanthate autoinjector can both increase total testosterone levels in hypogonadal men 3.
• Subcutaneous testosterone enanthate autoinjector may be associated with a more favorable safety profile, with lower post-therapy estradiol and hematocrit levels, compared to intramuscular testosterone cypionate 3.
• The choice of testosterone replacement therapy should be individualized, taking into account the patient's preferences and medical history 4, 5.