A systematic review of transgender male rodent model methodology.

Sixteen experimental rodent studies on transgender male GAHT were identified, conducted predominantly in mice.

• Studies were identified from PubMed, Embase, and Scopus databases from inception to August 1, 2024.
• 11 of 16 studies were performed on mice and 5 of 16 on rats.
• Study characteristics and methodology were extracted and compared across all 16 studies.

Weekly subcutaneous injections of testosterone enanthate was the preferred method of hormone administration across included studies.

• Subcutaneous (SC) pellets and SC silastic implants were also featured in some studies.
• Sesame oil was the preferred solvent for injected testosterone formulations.
• Methods varied largely across the 16 included studies.

Weekly doses of approximately 450 µg in mice and 420-900 µg in rats consistently induced testosterone levels comparable to male counterparts.

• Post-intervention circulating sex hormone concentrations were the primary outcome used to determine whether successful GAHT had been achieved.
• These doses were administered via subcutaneous injection.
• Achieving male-range testosterone levels was the benchmark for successful modeling of transgender male GAHT.

Subcutaneous silastic implants containing 10 mg of unesterified testosterone in mice or 10 mg/100 g in rats were also identified as successful methods.

• These implant doses successfully induced testosterone levels of the male counterpart.
• Silastic implants represent an alternative to injection-based administration in rodent TGM models.
• Both mice and rat dosing parameters were identified for this delivery method.

Most studies administered hormones for 6-8 weeks before performing post-treatment assessments.

• This duration was the predominant treatment period observed across the 16 included studies.
• The 6-8 week treatment window preceded the post-intervention outcome measurements including circulating sex hormone concentrations.
• Treatment duration was identified as a key methodological variable across studies.

Methods varied significantly across existing rodent models of transgender male GAHT, highlighting a need for standardization.

• The review aimed to assess existing methodology and how it influences circulating sex-hormone levels.
• The review identified effective methodological approaches intended to improve reproducibility and accuracy of preclinical models.
• The authors framed their findings as 'an integral step forward to bridging gaps in preclinical transgender healthcare research.'
• Recommendations of best practice were a stated goal of the systematic review.