Introduction: Transgender women with intact gonads receive lifelong hormonal treatment in order to suppress physiologic androgen production. Cyproterone acetate (CA) is the most comon antiandrogenic drug prescribed for this indication in Europe, with a dose range between 25-100 mg/day. Aim: To assess the effectiveness and safety of low dose (<20 mg/day), compared with high dose (>50 mg/day) CA treatment. Methods: Historical cohort study of transgender women treated in our department between January 2000 and October 2018. Results: There were 42 transgender women in the low dose group (LDG) and 32 in the high dose group (HDG). Age (27.9 ± 1.6 vs.28.9 ± 1.7 years) and follow up time (16.2 ± 2.2 vs. 20.1 ± 2.1 months) were similar in the LDG and HDG, respectively. At the last available visit, testosterone levels were effectively and similarly suppressed in both treatment groups (0.6 ± 0.1 vs 0.8 ± 0.3 nmol/l; p=0.37, for LDG and HDG respectively). Prolactin (659 ± 64 vs 486 ± 42 mIU/ml, p=0.02), LDL cholesterol (96.1 ± 5 vs 78.5 ± 4 mg/dl, p= 0.02) and triglycerides (93.3 ± 9 vs 69 ± 5 mg/dl; p=0.02) were higher in the HDG compared with LDG respectively. Side effects were common in the HDG (four cases of increased liver enzymes, one case of pulmonary embolism and one case of sudden death). Conclusion: We show for the first time that anti-androgenic treatment of transgender women with low dose CA is as effective as high dose treatment, but safer. We suggest incorporation of this observation in future guidelines.