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123 PROSTATE CANCER INCIDENCE UNDER ANDROGEN DEPRIVATION 8 INTRODUCTION Transgender people experience an incongruence between the sex assigned at birth and their experienced or expressed gender. 70 People assigned male at birth who identify as male are defined as cis men, and those who identify as female are defined as trans women. In the Netherlands, the prevalence of gender dysphoria in birth-assigned males is approximately 1 in 2,800. 71 Transgender people may choose medical treatment to align their physical characteristics with their experienced gender, including gender-affirming hormone treatment and gender-affirming surgery. Hormone treatment for trans women consists of anti-androgens combined with estrogens. 2 Although gender-affirming hormone treatment is generally considered safe, there may be risks and side effects, such as thromboembolic events or the development of sex hormone-related cancers (e.g. breast cancer). 4,135,136 Gender-affirming surgery involves bilateral orchiectomy, often combined with vaginoplasty and sometimes with breastaugmentation. 1 Although the prostate is biologically a male organ, prostatectomy is not performed during gender-affirming surgery because of the potential significant complications, such as incontinence. Therefore, trans women remain at risk for prostatic diseases after this procedure. It has been assumed that sex hormones, and androgens in particular, are involved in the pathogenesis of prostate cancer, because of the physiological dependency of prostate cells on androgens for functioning and proliferation. 22,23 In metastasized or advanced prostate cancer, androgen deprivation therapy is used to slow the progression of the disease. 24 However, a large meta-analysis showed no association between endogenous serum testosterone levels and prostate cancer incidence nor did it show an increased prostate cancer risk in hypogonadal men using testosterone replacement therapy. 25 Androgen deprivation therapy in cis men is primarily used in patients diagnosed with advanced prostate cancer and only sporadically for other indications, such as to control sex impulses in patients with severe paraphilias. 46 Therefore, there is currently very limited data available about a potential preventive effect of long-term androgen deprivation on the occurrence of prostate cancer. The primary aim of this study was to investigate the incidence of prostate cancer in trans women receiving androgen deprivation therapy and estrogens. Furthermore, this study gives a unique opportunity to study the potential preventive effect of androgen deprivation on the initiation and development of prostate cancer in general. METHODS Study design and data collection For this retrospective cohort study, data on subjects were obtained from their medical files including medical history, age at the start of hormone treatment, documented hormone use, and data on gender-affirming surgery.This database was linked to Nationwide Network