Testicular function

Is the testicular function of men and boys who received cancer treatment reduced in comparison to men and boys in the general population?

Cancer treatment, in particular chemotherapy and radiation, damages spermatogenic function in patients with cancer as the stem cells are immediately affected. Accordingly, sperm output falls rapidly and to a varying degree and duration (including being permanent). In addition, cancer treatment can as also be damaging to testicular Leydig cells, resulting in decreased testosterone levels. Hypogonadism is typically primary (testicular) hypogonadism in these cases, however certain cancer treatments may cause secondary (pituitary) hypogonadotrophic hypogonadism. Certain cancer treatments are more gonadotoxic than others, including platinum-based chemotherapies and radiation therapy.^[1][2][3][4]

Assessment of Sertoli cell function and sperm production utilises sperm count^{[5][1][6][7][8][9]} or surrogate measures such as follicle stimulating hormone (FSH),^{[5][10][10][1][6][7][11][12][13][8][9][14]} and inhibin B^{[5][1][13][8]} although inhibin B is typically measured in a research setting rather than in routine clinical practice. Although these markers give an indication of sperm production not sperm function, findings are consistent with impaired spermatogenesis in men and boys treated for cancer, with a reduced sperm count, raised FSH and decreased inhibin B.

Effects on sperm count or markers of spermatogenesis in men and boys treated for cancer are greatest with higher doses of cyclophosphamide and testicular irradiation[1], and cranial irradiation and chemotherapy, compared to radiotherapy alone^[13]. In a study of boys treated for cancer, those with Hodgkin and non-Hodgkin lymphomas, acute myeloid leukaemia, neuroblastoma and sarcoma had lower inhibin B levels and higher FSH levels than other cancer types,^[12] though it is important to note that in this study sperm counts often improved 24 months after treatment. Sperm concentrations were also lower in men previously treated for childhood lymphoblastic leukaemia compared to controls.^[6]

Assessment of Leydig cell function and testosterone production is measured by testosterone and luteinising hormone (LH). Testosterone was measured in all but one of the included studies,^{[4][5][10][15][1][16][6][7][2][11][12][3][13][8][9]} and LH was measured in most studies. Decreased testosterone levels and/ or increased LH levels were seen in many studies, with some larger studies identifying risk factors for hypogonadism, including a higher risk with BEP (bleomycin, etoposide, cisplatin) chemotherapy for testicular cancer, especially if LH was >8 U/L,^[4] more than four cycles of cisplatin, or cancers treated with radiation.^[15][1]

A study of men treated for unilateral testicular cancer and followed up for ten years showed hypogonadism risk was increased in those treated with surgery alone compared to controls (odds ratio 2.0), but the highest risk was in those treated with high dose cisplatin (odds ratio 7.9).^[2] Hypogonadism was present in 23% of men treated for childhood cancer compared to 4.3% of controls, especially in those with a history of testicular irradiation, brain tumours or chemotherapy treatment.^[3]

The highest level of evidence for loss of testicular function in men after cancer treatment comes from prospective cohort studies. One of the largest prospective cohort studies comes from the CECOS centres in France. Studies from this population have shown that lymphoma treatment had damaging effects on spermatogenesis,^[17] as did adjuvant treatments for testicular germ cell tumor^[18]. Significant sperm aneuploidy was induced in lymphoma ^[19] and men with testicular cancer ^[20].

Other prospective cohorts have also demonstrated greater damage to sperm DNA in men with testicular cancer and lymphoma^[21] as well as premature hormonal ageing in men previously treated for testicular cancer.^[22].