The effects of gender-affirming testosterone therapy on reproduction in a transmasculine mouse model
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Abstract
BACKGROUND: In recent years, there has been a large number of individuals that identify as transgender, with approximately 0.5% of the population identifying as transgender or non-binary. In line with the current standards of care, some of these individuals, desire gender-affirming care such as hormonal therapy to align their secondary sex traits with their identified gender. While numerous studies have explored how gonadal hormones influence the brain and the reproductive system, emerging research is being conducted on the impact that gender-affirming gonadal hormones have on transgender people. For this reason, some scientists have developed transgender rodent models to further our understanding of the physiological impact of gender-affirming hormones. OBJECTIVE: The aim of our research was to create a transmasculine mouse model, recapitulating the approach to treatment in humans, and assess the reproductive phenotype.
METHODS: 40 eight week old wild type C57BL/6 mice, including 30 females and 10 males were injected with testosterone enanthate or vehicle weekly for 6 weeks to measure changes in their reproductive phenotype. The 30 female mice were divided equally into three groups and injected with testosterone enanthate (Sigma SML3730) subcutaneously (SQ) or sesame oil weekly for six weeks (Figure 5). The Female Low T group was injected with 0.45 mg of testosterone enanthate and the Female High T group was injected with 0.90 mg of testosterone enanthate, and the Female Vehicle group was injected with sesame oil as a control. The Male Vehicle group was also injected with sesame oil, similar to the Female Vehicle group and served as an additional control group. This study measured serum testosterone and luteinizing hormone concentrations, as well as changes in body weight, body length, clitoral length, and estrous cyclicity.
RESULTS: Our results showed that both testosterone-treated female mice groups had an increase in body weight, body length, as well as clitoral length in the setting of serum testosterone levels in the male range. Additionally, both testosterone-treated groups displayed decreased serum luteinizing hormone concentrations and loss of estrous cyclicity.
CONCLUSION: In conclusion, this preclinical model of T-GAHT in female mice displayed an altered reproductive phenotypes and can be used for future studies to understand the impact on fertility in mice.
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2025