Subcutaneous Testosterone Project
Condition: Gender Dysphoria
MeSH terms: Gender Dysphoria
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      For people who identify as transgender, there is a strong sense that they were born into the
      wrong body and that their outward looking body does not match how they truly feel about
      themselves. They feel male, not female and have always felt that way. There is a great deal
      of discomfort or dysphoria about looking and feeling female, and there is a strong desire to
      achieve a more masculine appearance. While surgery, clothing and hair for example, can help a
      person appear more like a male, many transgender males will want to take testosterone to make
      them feel and look more masculine.

      This usually involves injecting testosterone into a muscle every 1-2 weeks for many years.
      Intramuscular injections can often be uncomfortable or painful, and requires the patient to
      be taught how to inject themselves. Or somebody else has to do it. There is a growing trend
      in some transgender men to give their injection just below the skin or subcutaneously (like
      insulin in a diabetic), because it is less uncomfortable but we don't really know if
      testosterone gets into the blood in the same way. At least one clinic in the US already
      suggests that patients can use the subcutaneous method but there is almost no research to
      show it's the same as intramuscular.

      Our project will be looking at a small group of transgender males who are already on
      intramuscular testosterone and then switch them over to the same dose of subcutaneous
      testosterone, and then compare their levels of testosterone. If those levels are similar,
      then patients may chose the less uncomfortable subcutaneous injection.
    

Detailed description: 
      Rationale:

      In caring for transgender males (born female but identify as male), intramuscular (IM)
      testosterone is considered standard of care if they elect therapy to transition. Yet, IM
      testosterone has limitations: discomfort; a modest amount of teaching; bleeding concerns if
      the patient is on anticoagulants; and fluctuations in circulating serum testosterone. Erratic
      absorption may also led to variability in mood and energy. Due to these limitations, there is
      a trend, especially in younger patients, to use the more comfortable subcutaneous (SC) route.
      However, there are little data suggesting equivalency of SC to IM testosterone and virtually
      no data in transgender males.

      Hypothesis:

      In transgender males, SC testosterone will yield similar pharmacokinetics and better
      tolerability when compared to IM testosterone.

      Objectives:

        1. To validate, using a cross-over design, whether pharmacokinetic parameters of SC vs. IM
           testosterone administration are similar.

        2. To characterize, using a validated pain questionnaire and patient diary, tolerability of
           SC vs. IM testosterone.

      Research Plan:

      Patients (19-59 years old) on a weekly self-injection schedule of either T cypionate or
      enanthate will be included. Patients with medical instability, recent or imminent surgery
      will be excluded. Twenty-five patients will be recruited from the 6 local Vancouver Coastal
      HealthTrans Primary Care physicians' clinics.

      Using a cross-over design, trough serum testosterone levels from the IM technique will be
      determined weekly for 3 weeks. Patients will then switch to SC injection of the same
      testosterone ester and dosage, and weekly trough levels measured for another 8 weeks. These
      trough measurements will allow us to determine attainment of steady-state testosterone
      levels. During the 3rd and 11th week, serial testosterone levels will be collected to
      generate noncompartmental pharmacokinetic parameters, which will be compared between the two
      techniques. Patients will complete a validated pain analogue questionnaire during the initial
      3-week IM phase, and again during weeks 2 and 8 of the SC phase and maintain a diary
      throughout the study. Descriptive and inferential statistics will be used with p<0.05
      denoting significance.

      Significance: If SC testosterone yields similar pharmacokinetics and better tolerability than
      IM testosterone, it will reduce the perceived barrier of IM injections and mitigate
      non-compliance. There are potential cost savings as patients will not require a clinician to
      inject. The findings may also be generalized to hypogonadal males. Ultimately, results are
      crucial to designing a larger multi-center study to provide definitive dosing
      recommendations.
    

Intervention name(s): Subcutaneous testosterone
Intervention type(s): Drug
Other intervention name(s): Testosterone cypionate; Testosteron enanthate
Intervention MeSH terms: Methyltestosterone; Testosterone; Testosterone undecanoate; Testosterone enanthate; Testosterone 17 beta-cypionate
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Intramuscular testosterone; Subcutaneous testosterone