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129 PROSTATE CANCER INCIDENCE UNDER ANDROGEN DEPRIVATION 8 castration-resistant prostate cancer. Different theories suggest that castration-resistant prostate cancers have developed mechanisms that enable them to use steroids from the circulation more efficiently through de novo androgen synthesis, changed function of the androgen receptor, or even through estrogen receptor signaling pathways. 145,146,152 European guidelines advice against systematic population-based PSA screening for prostate cancer, since it does not increase survival and causes overtreatment. 153 Following these guidelines, routine population-based PSA screening, in both cis men and trans women, is not performed in the Netherlands. PSA testing is only recommended in people with an elevated risk of prostate cancer after counselling on the potential risks and benefits. 21 Given the low incidence of prostate cancer and lack of PSA reference values in this population, there is even less reason to perform routine screening in trans women. However, it remains important that trans women and their health care providers are aware of the presence of the prostate and the possibility of the development of prostate cancer despite low serum androgen levels. This study provides novel insights into prostate cancer risk in trans women receiving androgen deprivation and estrogen treatment.The major strengths of our study include the large cohort size consisting of people with a wide age range and the validation of our data by linking our cohort to the Dutch national pathology database. Also, our study has a long follow-up period which is adequately calculated using data on mortality from Statistics Netherlands. Furthermore, since the current practice for prostate cancer screening in the Netherlands is the same for cis men and trans women, i.e. no routine PSA testing, the role of detection bias in this study seems to be very limited. A limitation of this study is the lack of information about the clinical symptoms of the six trans women with prostate cancer that led to the diagnosis, since the majority were diagnosed and treated in other hospitals than our clinic. Furthermore, information about family history, hormone use, and lifestyle, was missing or incomplete due to the retrospective design of our study. In particular, data on family history would have provided more insight into the genetic susceptibility for prostate cancer, which is known to be an important risk factor. 154 Although the influence of these risk factors on prostate cancer should not be underestimated, the most profound difference between our cohort and the reference population is gender-affirming treatment with anti-androgens and estrogens and eventually orchiectomy. For future studies, it would be worthwhile to investigate the clinical symptoms in trans women leading to prostate cancer diagnosis. Further research is needed to understand the pathogenesis of prostate cancer in trans women receiving hormone treatment and how this influences treatment outcome compared to cis males.