Iris de Nie

136 C H A P T E R 9 affected in those who initiated medical treatment as adults compared to those who initiated treatment during adolescence, despite the lower mean duration of medical treatment prior to GAS. A higher percentage of hyalinization of the seminiferous tubules was observed in the adult subgroup, as well as a complete absence of germ cells in 11% of orchiectomy specimens. The difference between the adult subgroup and the adolescent subgroups might be explained by age, lifestyle, higher dosages of estradiol, or the use of cyproterone acetate instead of GnRHa as testosterone suppressing therapy. The use of GAHT may not only result in incomplete spermatogenesis and hyalinized seminiferous tubules, but might also affect testicular carcinogenesis. Specifically, a relative excess of exogenous estrogens during pre- or post-natal life (e.g. diethylstilbestrol, pesticides) is suggested to play a causal role in the development of testicular cancer. 17-19 To assess the safety of hormone treatment in terms of testicular cancer risk, we conducted a study to evaluate the incidence of testicular cancer in trans women using GAHT. As described in chapter 7 , we observed a total of three testicular cancer cases in our cohort, of which two were discovered due to symptoms and the third was encountered during routine histopathological analysis of the bilateral orchiectomy specimen. Based on age- specific incidence rates in cis men, a similar amount of testicular cancer cases would have been expected, which suggest that testicular cancer risk in trans women is comparable to the risk in cis men. Furthermore, results from a subgroup analysis in trans women with a long follow-up period, suggest that longer exogenous estrogen exposure does not increase the risk for the development of testicular cancer. The prostate is another part of the male genital tract that may be influenced by GAHT, since prostate cells are physiologically dependent on androgens for functioning and proliferation. 22,23 A paradox in the current knowledge is that, on the one hand, androgen deprivation slows the progression of metastasized or advanced prostate cancer, while, on the other hand, higher endogenous serum testosterone or elevating testosterone concentrations in hypogonadal men do not increase prostate cancer risk. 24,25 In trans women the prostate is not removed during gGAS because of the potential significant complications, such as incontinence. Therefore, they remain at risk for prostatic diseases after this procedure. In the study described in chapter 8 ,we assessed the prostate cancer incidence in trans women using GAHT and we hereby studied the potential preventive effect of androgen deprivation on the occurrence of prostate cancer. In line with our hypothesis, we found a 5-fold decrease in prostate cancer risk in trans women using GAHT compared with the general male population of similar age which confirms a preventive effect of androgen deprivation on the initiation and development of prostate cancer in general. METHODOLOGICAL CONSIDERATIONS The studies presented in this thesis have several strengths. In the majority of our studies we included large populations, especially in comparison with previous studies conducted on these topics. This allowed us to include multiple variables in the association models assessing the effect of certain factors on semen quality, and to perform subgroup analyses