Abstract 077: 17b-estradiol Implants With An Antiandrogen Or Castration Attenuate Body Weight And Total Lean Mass But Differentially Modulate Total Cholesterol And The Pressor Response To Chronic Angiotensin II In The Male Rat

Abstract

Background: Transfemales are biological males at birth, but identify as female by gender. Gender-Affirming Hormone Therapy ( GAHT ) is used to alter hormone levels to match gender identity. GAHT in transfemales involves administration of estradiol ( E2 ) with an androgen antagonist ( AA ) or orchiectomy. Sex is an independent predictor of cardiovascular ( CV ) risk, but the role of sex hormones on CV risk in transfemales is unknown. Thus, this study tested the hypothesis that GAHT in male rats increases CV risk. Methods: Male Sprague Dawley ( SD ) rats were randomly assigned at 14 weeks of age to three groups that underwent either mean arterial pressure ( MAP , N=3-5/group) or metabolic (N=8/group) monitoring. Control ( C ): empty silastic capsule. E2+AA: silastic capsule with 17-beta E2 benzoate (5 mg/21 days) plus AA, spironolactone (10 mg/kg/day, incorporated in diet). E2+CTX: silastic capsule with E2 plus castration ( CTX ). Silastic capsules (+/- E2) were replaced every 21 days starting at 14 weeks. AA, started at 14 weeks of age, was continued in E2+AA but discontinued after CTX at 16 weeks of age in E2+CTX. Results: (Table 1) : The pressor response to angiotensin II ( ANG II ) was similar in C and E2+CTX but was blunted in E2+AA despite similar baseline MAP, increase in E2 and decrease in testosterone. Cholesterol was only increased in E2+AA. Conclusion: These results suggest that feminizing therapy in male rats is associated with similar changes in sex steroids but the pressor response to ANG II and lipid profile differ based on the method of androgen reduction. The use of a transfemale rodent model will allow study of the pathophysiology of increased CV risk associated with GAHT across the lifespan.