Testicular cancer; gonadal, sexual and psychological aspects of the disease and its treatment.

Abstract: The survival rates among testicular germ cell cancer (TGCC) patients have dramatically increased and more than 95 % are cured. The question of quality of life of the survivors is, therefore, important. The TGCC treatment, and thereby its side-effects may vary. A contributing factor to this variation is also genetically determined inter-subject difference in the sensitivity to the adverse effects of cancer therapy. The aim of this thesis has been, in order to improve the management and counselling of TGCC patients, to increase the level of knowledge regarding impairment of reproductive functions as well as the risks of emotional disorders (EMD) related to TGCC and its treatment. In article I, impact of therapy and androgen receptor (AR) polymorphisms on sperm concentration was investigated. Radiotherapy (RT) or 3 to 4 cycles of chemotherapy (SCT) caused initial decline in sperm concentration, which returned to pre-treatment levels 2 to 5 years after therapy. In the SCT group, sperm concentration 1 to 2 years post-treatment was inversely correlated to the androgen receptor (AR) CAG repeat length, indicating a genetic variation in the recovery of sperm concentration. In article II, risk factors for developing hypogonadism were studied. SCT and RT treated were at higher risk of hypogonadism, 6 and 12 months post-treatment as compared to those who received 1 to 2 cycles of chemotherapy. Microlithiasis and hormone deficiency prior to treatment predicted increased risk of hypogonadism after cancer therapy. In article III, TGCC patients, 3 to 5 years after treatment, were compared to the general population concerning prevalence of sexual dysfunctions. A higher proportion of TGCC patients had low sexual desire and erectile dysfunction. Neither hypogonadism nor treatment modality had any obvious impact on the risk of these sexual problems. In article IV, the presence of EMD was investigated, 3 to 5 years after TGCC therapy and related to hypogonadism, AR polymorphisms and treatment modality. Neither anxiety nor depression was overrepresented in hypogonadal TGCC patients and no association between AR polymorphisms and EMD was found. Patients treated with than four cycles of cisplatinum based chemotherapy due to refractory or relapsed disease were more prone to experiencing symptoms of anxiety.