Iris de Nie

13 GENERAL INTRODUCTION AND THESIS OUTLINE 1 Cancers of the male genital tract The male genital tract compromises the penis, testes, epididymes, vas deferens, seminal vesicles, and the prostate. The most common cancers within the male genital tract, in order from least to most frequent, are penile, testicular and prostate cancer. In this thesis we will only focus on testicular and prostate cancer because of the potential influence of sex steroids on the development of these malignancies, as opposed to penile cancer which is mainly associated with being infected with Human Papilloma Virus. 14 Testicular cancer mainly occurs in young people; the incidence in the Netherlands is 9.5 per 100.000 men, with a peak incidence of 32.4 per 100.000 men in those between 30-34 years old. 15 Testicular cancers can roughly be divided into sex cord or gonadal stromal tumors and germ-cell tumors, of which the latter most commonly occur. Germ-cell tumors are further classified as seminoma, non-seminoma and mixed germ-cell tumors. Prognosis, depending on histology, location of the primary tumor and metastases, and serum tumor marker levels, is generally better for seminoma compared to non-seminoma. 16 Although the incidence has increased over the past 40 years in most countries, the etiology of testicular cancer and the reasons for this rise remain unclear. Established risk factors for testicular cancer are a history of cryptorchidism, a low sperm count, presence of a contralateral testis tumor or a positive family history among first-grade relatives for testicular cancer. 16 Some theories also suggest that a relative excess of exogenous estrogens during pre- or post- natal life (e.g. diethylstilbestrol, pesticides) may play a causal role in the development of testicular cancer. 17-19 Prostate cancer is the second most common cancer in men worldwide, accounting for approximately 15 per cent of all new cancers with incidence mainly dependent on age. 20,21 Other risk factors include genetic factors such as a positive family history and an African ethnicity. 21 It has been assumed that sex hormones, and androgens in particular, are involved in the pathogenesis of prostate cancer, because of the physiological dependency of prostate cells on androgens for functioning and proliferation. 22,23 In metastasized or advanced prostate cancer, androgen deprivation therapy is used to slow the progression of the disease. 24 However, a large meta-analysis showed no association between endogenous serum testosterone levels and prostate cancer incidence nor did it show an increased prostate cancer risk in hypogonadal men using testosterone replacement therapy. 25 There is currently very limited data available about a potential preventive effect of long-term androgen deprivation on the occurrence of prostate cancer. Influence of gender-affirming treatment on the male genital tract Asmentioned above,under the influence of GAHTsubstantial changes occur in sexual function and the male genital tract.Trans women often experience a decrease in sexual desire as well as an increase in the time being comfortable without sexual activity, after initiating GAHT. 26 Furthermore, the low levels of serum testosterone result in an increased rate of erectile dysfunction and a decreased volume of the prostate and testes. Another consequence