Iris de Nie

112 C H A P T E R 7 GAHT, who are still at risk for testicular cancer. Several studies have been conducted on the influence of androgen deprivation, estradiol supplementation, or a combination of these two, on testicular tissue and showed incomplete spermatogenesis, a decreased diameter of seminiferous tubules, and increased peritubular hyalinization. 28,29,104,125 However, very little is known about the influence on the occurrence of testicular cancer and only a few cases of testicular cancer in trans women using GAHT have been reported. 41-45 The primary aim of this study was to evaluate the incidence of testicular cancer in trans women using GAHT and, hereby, assess the safety of hormonal treatment in terms of testicular cancer risk. A secondary aim was to assess the outcome of histopathological analyses of orchiectomy specimens obtained during GAS. METHODS Study design and population For this nationwide retrospective cohort study, we identified all people who visited the gender identity clinic of the Amsterdam UMC between 1972 and September 2017. Approximately 95% of all transgender people in the Netherlands visit our center for either psychological, endocrine, or surgical treatment. Since only trans women using GAHT were eligible for inclusion, people who never used GAHT, those who underwent bilateral orchiectomy prior to the start of GAHT, or those of whom the start date of GAHT was unknown, were excluded. Other exclusion criteria involved being under 18 years of age at the time of the study (2020), or having used female and male hormones alternatingly during the follow-up period. Lastly, since data were partially obtained from the Dutch national pathology database (PALGA), which covers histopathologic diagnoses nationwide since 1991, trans women were also excluded when their last visit to the gender identity clinic was before 1991. 126 Hormonal treatment for trans women generally consists of a combination of antiandrogens and estrogens. The most commonly prescribed antiandrogen in this cohort was cyproterone acetate (10 to 100 mg daily) and only sporadically spironolactone (100 to 200 mg daily) was used. Different administration routes for estrogens exist, such as transdermal, oral and intramuscular formulations. The different types of estrogens prescribed in our center included estradiol patches (50 to 150 µg/24 hours twice weekly), estradiol gel (0.75 to 3.0 mg daily), estradiol valerate (2 to 6 mg daily), ethinyl estradiol (25 to 100 µg daily), conjugated estrogens (0.625 to 1.25 mg daily), estradiol implants (20 mg every 3 to 6 months), and estradiol injections (10 to 100 mg every 2 to 4 weeks). From 2001 onward, mainly estradiol patches, estradiol gel, or estradiol valerate were used. People who started hormonal treatment when they were younger than 18 years, often used GnRHa, namely triptorelin, prior to the start with estrogens, and continued this medication until orchiectomy. The Ethical Review Board of the VU University Medical Center Amsterdam, concluded that the Medical Research Involving Human Subjects Act (WMO) did not apply to this study.