Iris de Nie

118 C H A P T E R 7 women obtained during GAS. 104,119 To the best of our knowledge this is the first reported case of testicular cancer discovered during histopathological analysis of an orchiectomy specimen, even though our center implemented routine histopathological analysis of orchiectomy specimens obtained during GAS approximately ten years ago. For trans women who underwent bilateral orchiectomy outside the Netherlands or before routine histopathological analysis was implemented, no histology results were available. Since testicular cancer was discovered in only 0.1% of the 722 analyzed orchiectomy specimens, one can argue if this routine histopathological analysis is necessary when there is no suspicion of testicular pathology. In literature, exposure to estrogens has been implicated as a risk factor for germ cell tumors. Studies in rodents have shown that exposure to high estrogen levels during either pre-natal or adult life induces testicular tumor formation, however it is unclear how such findings in animals apply to humans. 132 Several epidemiological studies have found a possible association between exposure to occupational and environmental estrogenic chemicals, such as pesticides and other endocrine disrupting agents, and increased testicular cancer risk but require further confirmation. 17-19,133 Also, studies have investigated the association between high maternal estrogen levels during the first trimester of pregnancy and the development of testicular cancer in offspring but failed to produce clear evidence for this estrogen excess hypothesis. 18,134 Limitations of these studies, however, include the indirect parameters that are used to assess the effect of estrogen exposure such as maternal age > 30 years, being first-born, and twinning. We feel that, with our current study, we are able to more directly assess the influence of estrogens on testicular cancer risk, since the most profound difference between our cohort and cis men is the use of gender-affirming hormones. As we found that testicular cancer risk in trans women is not increased compared to cis men, our results do not support the hypothesis of a carcinogenic effect of post-natal exposure to exogenous estrogens on testicular tissue. The major strengths of our study include the large cohort size consisting of young people with an age range in the peak incidence of testicular cancer. Also, follow-up time is adequately calculated by using the date that people were no longer at risk for testicular cancer or when they were last seen at our gender clinic. Furthermore, we were able to validate our data by linking our cohort to the Dutch national pathology database which has nationwide coverage. 126 Taken these factors into account, we feel that we are the first to report a reliable estimate of the testicular cancer risk in trans women. A limitation of this study is that, despite the large cohort size, follow-up time is relatively short due to the fact that the majority of trans women decided to undergo bilateral orchiectomy directly after the required minimum of twelve months GAHT. Nonetheless, within the subgroup of 523 trans women using hormonal treatment for at least 5 years (median 8.9 years, range 5.0-52.1), no testicular cancer cases were observed, implying that a longer duration of hormonal treatment does not contribute to an increased testicular cancer risk. It might be worthwhile to repeat this study in ten years, to establish a larger