Iris de Nie

139 GENERAL DISCUSSION AND FUTURE PERSPECTIVES 9 it seems even more harmful to deprive young transgender adolescents from treatment. Therefore, it is of utmost importance to find a way for fertility preservation for those who are unable to pursue semen cryopreservation prior to the initiation of treatment. The results of our study on testicular tissue obtained at time of GAS seem promising, since in a small percentage of trans women (who initiated treatment in Tanner stage 4 or higher) mature spermatozoa could have been harvested from the orchiectomy specimen ( chapter 6 ). Furthermore, in all adolescents there were still germ cells present in the orchiectomy specimen. However, the downside of harvesting germ cells from testicular tissue is that such spermatozoa can only be used for invasive and expensive ICSI treatments, and the use of immature germ cells require techniques that are currently still experimental and far from the clinical realm. Therefore, cryopreservation of a semen sample prior to initiation of GAHT remains the preferred method of fertility preservation in transgender women, and harvesting germ cells from orchiectomy specimens might only be a considerable alternative in those for whom this is not an option. Another interesting observation in the histological study on testicular tissue obtained at time of GAS was that seminiferous tubules and spermatogenesis seemed more negatively affected in trans women who initiated GAHT during adulthood ( chapter 6 ). This may be related to the use of cyproterone acetate instead of GnRHa as testosterone suppressing therapy. Whereas GnRHa only leads to inhibition of gonadotropin secretion, cyproterone acetate also has progestative effects and acts as a direct antagonist of the androgen receptor. It hereby inhibits the influence of androgens on the androgen-dependent organs, among which the testes. The latter might have more profound and irreversible effects on testicular tissue. Because of unwanted side-effects of cyproterone acetate (e.g. increased risk for meningioma), transgender women commencing GAHT in our clinic above the age of 18 years now receive GnRHa as testosterone suppressing therapy instead of cyproterone acetate. The potential consequence of irreversible infertility might be an extra reason to not prescribe cyproterone acetate anymore. Since several years, an increasing number of people with non-binary identities or less need to confirm to binary cis presentation, choose to keep their male gonads. Therefore, the results of our study assessing the influence of GAHT on testicular cancer risk become increasingly relevant ( chapter 7 ). Our observation that testicular cancer risk in trans women is similar to the general population, and did not seem related to a longer period of exogenous estrogen exposure, is reassuring for trans women who do not wish to undergo genital GAS. Since guidelines advice against population-based screening for testicular cancer in cis males, and no increased risk exist in trans women, there seems to be no reason for extra precautions in the gender diverse population. However, awareness of the presence of the gonads remains important and regular testicular self-examination is recommended. Our findings also raise the question if it is still necessary to perform routine histopathological analysis of orchiectomy specimens when there is no suspicion of testicular pathology, since testicular cancer was discovered in only 0.1% of the 722 analyzed orchiectomy specimens. Especially, in cases where this tissue may be used for fertility preservation purposes instead.