Abstract Introduction Many transgender and gender diverse (TGD) individuals seek medical gender-affirming hormone treatments (GAHT), including pubertal blockade and cross-sex hormone therapy., including pubertal blockade and cross-sex hormone therapy. However, there is limited research on the long-term health impacts of GAHT on body health in both rodents and humans. Objective We aimed to establish a GAHT model for feminization in C57Bl/6 mice from adolescence to adulthood. Methods Ethical approval CEUA/UFF 9356200224. In adolescence (6 weeks old), male C57BL/6 mice received a pubertal blockade with leuprolide (20 μg/day) for 6 weeks, followed by hormonal therapy in adulthood (3 to 6 months old) with estradiol (E 2, 30 μg/week) alone or combined with cyproterone acetate (Cyp) at low and high doses (2 or 20 mg/kg/day on drinking water) for 12 weeks. Data are expressed as mean ± SD, with group comparisons conducted by one-way ANOVA with Tukey’s post hoc test (p0.05). Results In adolescence, control mice had 19.8±2.0g of body mass (BM), which increased by 16.7% at 3 months old (p=.004) and 33.4% (p=.002) at 6 months old. GAHT mice showed a similar BM increase, with no modulation by either leuprolide in adolescence or hormonal therapy in adulthood. At 6 months, muscle mass (gastrocnemius /soleus) also showed no difference among groups (p0.45). Testis weight in control mice was 178.9 ± 34.1 g, and the gonadosomatic index (GSI) was 0.68 ± 0.12g/g%. While GAHT did not affect these parameters (p.23), it decreased sperm count and motility in all groups treated with E2 and E2/Cyp low and high doses. Finally, GAHT with E2/Cyp low and high doses resulted in bladder, seminal vesicles, and prostate atrophy (summed weight) similarly when compared to control mice (-23.7%, p = 0.0069 and -28.9%, p = 0.001, respectively). Conclusions Male-to-female transition was successfully achieved by combining estradiol and low-dose cyproterone acetate after pubertal blockade with leuprolide. Although testis weight remained unchanged, reductions in sperm count and seminal vesicle size indicate suppressed testosterone production. The following steps include examining the external genitalia, sperm, and testis morphology. Supported by FAPERJ and CNPq grants Disclosure No
Sampaio et al. (Mon,) studied this question.