Body, metabolic and renal changes following cross-sex estrogen/progestogen therapy in a rodent model simulating its use by transwomen

Purpose The use of sex steroids by trans people has been of paramount importance regarding body changes during gender transition. The objective of this study was to assess the effects of an injectable steroid combination frequently used by transwomen, namely estradiol enanthate with dihydroxyprogesterone acetophenide (E2EN/DHPA), on blood pressure and metabolic outcomes using an animal model. Methods Two-month-old male Wistar rats were orchiectomized or sham-operated and divided into groups: (1) Sham treated with sesame oil vehicle (SG), (2) sham treated with E2EN/DHPA (SP), (3) orchiectomized rats treated with vehicle (OG), and (4) orchiectomized rats treated with E2EN/DHPA (OP), with all groups treated every 10 days for 5 months. We evaluated systolic blood pressure (SBP), body weight (BW), abdominal circumference, nasoanal length (NAL), food and water intake (FI, WI), lipid profile (triglycerides, LDL, and HDL), serum C-reactive protein (CRP), plasma concentrations of urea (URpl) and creatinine (CRpl), 24 h urinary volume (V24 h), sodium and potassium excretion (UNa + , UK + ), and proteinuria. Results E2EN/DHPA administration reduced BW (SP 324.5 ± 31.1; OP 291.7 ± 41.3 g) and NAL (SP 24.5 ± 0.4; OP 24.6 ± 1.0 cm), without changing blood pressure, but increased URpl concentration (SP 55.0 ± 4.8; OP 42.5 ± 8.8 mg/dL) and CRpl (SP 0.47 ± 0.05; OP 0.46 ± 0.04 mg/dL), sodium (SP 3.1 ± 0.8; OP 3.3 ± 0.4 µEq/min/kg), potassium (SP 0.91 ± 0.22; OP 0.94 ± 0.22 µEq/min/kg) excretions and urinary volume (SP 15.5 ± 2.1; OP 16.4 ± 2.9 mL/24 h). Conclusion Cross-sex hormone therapy with E2EN/DHPA significantly modified body characteristics in male rats, producing a feminizing change without altering blood pressure or generating harmful metabolic parameters, but larger translational studies are still needed.