Preclinical Murine Model of Gender-Affirming Hormone Therapy

Background: Gender-affirming hormone therapy (GAHT) is a common part of transgender medical care, involving the alteration of sex hormone levels. Although sex hormones are known to be implicated in kidney health and disease, few studies have explicitly examined the effects of GAHT on kidney health. Methods: Male and female C57Bl6/J mice were used. At 8 weeks of age, males were implanted with 17β-estradiol (E2) and spironolactone pellets (MH), or dose matched placebo pellets (MP). Female mice were implanted with a testosterone (T) pellet (FH), or a dose-matched placebo pellet (FP). Untreated male (MQ) and female (FQ) mice were used as comparators. During the hormonal acclimation, 24 hour urine was collected, and body composition, glomerular filtration rate (GFR), and plasma creatinine (PCr) were measured. After 11 weeks of acclimation, mice were euthanized, and tissues were collected. Plasma was collected at euthanasia. Results: MH had higher E2 level compared to MQ, although T levels were not different. FH did not have different E or T levels compared to FP or FQ. Percent lean and fat mass did not differ between groups. IL2 in MH were decreased compared to MP, but no differences were noted in the female groups. IL5 in FH were slightly lower than FP and FQ, although significance was not reached. In MH, bone mineral density sharply increased; no significant changes were noted in other groups. No differences in PCr were noted between groups, although all groups experience a sharp increase during the acclimation, which resolved. GFR remained stable across time. Kidney expression of KIM-1 and NGAL was not detected in any groups. At 10 weeks of hormonal acclimation, an increase in urine creatinine was noted in both MH and FH. Conclusion: Administration of exogenous sex hormones in a murine model does not independently cause kidney damage. Although a spike in PCr was noted, GFR remained stable, which may indicate an extra-renal cause. Slight modulations in cytokine levels may indicate changes in an inflammatory milieu that would be further reflected with kidney injury. Although FH did not have significantly different T levels than FP and FQ, differences in other parameters, including cytokine expression and urine creatinine, may indicate that T administration may have an effect on parameters affecting kidney function. Funding: NIDDK Support