ORIGINAL PAPER
Treatment-related gonadotoxicity in young male cancer survivors: a comparative cross-sectional study
 
More details
Hide details
 
Publication date: 2018-03-19
 
 
Pediatr Pol 2018;93(1):23-29
 
KEYWORDS
ABSTRACT
Introduction:
Male gonads are susceptible to the deleterious effect of anticancer therapy (chemotherapy, radiation to the pelvis, central nervous system, or total body irradiation). Hormonal dysfunction after anticancer treatment was evaluated in young male cancer survivors.

Material and methods:
In 153 male adolescent cancer survivors divided into three risk groups (low-LR, moderate-MR, and high-HR) and 24 controls, gonadal and pituitary hormones were analysed. FSH, LH, and testosterone levels were assessed in all the studied patients using immunoenzymatic techniques, dimeric inhibin B – by ELISA method.

Results:
All cancer survivor groups had lower mean values of inhibin B (86.87 ±69.07 ng/l vs. 161.07 ±60.64 ng/l; p < 0.001), and higher FSH (10.23 ±13.35 mIU/l vs. 4.38 ±2.39 mIU/l; p < 0.001) and LH (5.0 ±3.43 IU/l vs. 3.58 ±2.17 IU/l; p = 0.016); testosterone levels were comparable to the controls. Abnormal values of inhibin B were found: in 15.2% of survivors in LR, 47.6% in MR, and 94.1% – in the HR group. Elevated FSH levels were seen in 20.4% of survivors in LR, 47.4% in MR, and 92.2% in the HR group. The inhibin B: FSH ratio was lowered in MR and HR risk groups. We did not observe any influence of the age at treatment and the time since treatment termination on the analysed hormonal values.

Conclusions:
Anticancer treatment increases the risk of gonadal damage, particularly in the HR group. Patients and parents ought to be informed about the risk of lowered reproductive function, and pretreatment semen cryopreservation should be recommended.
REFERENCES (38)
1.
Bhatia S, Constine LS. Late morbidity after successful treatment of children with cancer. Cancer J 2009; 15: 174-180.
 
2.
Marques P, Van Huellen H, Fitzpatrick A, et al. Late endocrine effects of cancer and cancer therapies in survivors of childhood malignancies. Minerva Endocrinol 2016; 41: 78-104.
 
3.
Çağlar AA, Oğuz A, Pınarlı FG, et al. Thyroid abnormalities in survivors of childhood cancer. J Clin Res Pediatr Endocrinol 2014; 6: 144-51.
 
4.
Brignardello E, Felicetti F, Castiglione A, et al. Gonadal status in long-term male survivors of childhood cancer. J Cancer Res Clin Oncol 2016; 142: 1127-1132.
 
5.
Gunn HM, Rinne I, Emilsson H, et al. Primary gonadal insufficiency in male and female childhood cancer survivors in a long-term follow-up clinic. J Adolesc Young Adult Oncol 2016; 5: 344-350.
 
6.
Kenney LB, Cohen LE, Shnorhavorian ML, et al. Male reproductive health after childhood, adolescent, and young adult cancers: a report from the children’s oncology group. J Clin Oncol 2012; 30: 3408-3416.
 
7.
Nandagopal R, Laverdiere C, Mulrooney D, et al. Endocrine late effects of childhood cancer therapy: a report from the children’s oncology group. Hormone Res 2008; 69: 65-74.
 
8.
Green DM, Liu W, Kutteh WH, et al. Cumulative alkylating agent exposure and semen parameters in adult survivors of childhood cancer: a report from the St Jude Lifetime Cohort Study. Lancet Oncol 2014; 15: 1215-1223.
 
9.
Wallace WH, Anderson RA, Irvine DS. Fertility preservation for young patients with cancer: who is at risk and what can be offered? Lancet Oncol 2005; 6: 209-218.
 
10.
Crofton PM, Thomson AB, Evans AEM, et al. Is inhibin B a potential marker of gonadotoxicity in prepubertal children treated for cancer? Clin Endocrinol 2003; 58: 296-301.
 
11.
Krawczuk-Rybak M, Solarz E, Wojtkowska M, et al. Gonadal function in young men after the treatment for Hodgkin lymphoma. Pediatr Endocrinol Diabetes Metab 2009; 15: 85-92.
 
12.
Krawczuk-Rybak M, Panasiuk A, Muszynska-Rosłan K, et al. Health status of Polish children and adolescents after ending of anticancer treatment. Polish Oncol 2012; 15: 96-102.
 
13.
Chada M, Prusa R, Bronsky J, et al. Inhibin B, follicle stimulating hormone, luteinizing hormone and testosterone during childhood and puberty in males: changes in serum concentrations in relations to age and stage of puberty. Physiol Res 2003; 52: 45-51.
 
14.
Green DM, Zhu L, Zhang N, et al. Lack of specificity of plasma concentrations of inhibin B and follicle stimulating hormone for indentification of azoospermic survivors of childhood cancer: a report from the St Jude lifetime cohort study. J Clin Oncol 2013; 31: 1324-1328.
 
15.
Tromp K, Claessens JJ, Knijnenburg SL, et al. Reproductive status in adult male long-term survivors of childhood cancer. Hum Reprod 2011; 26: 1775-1783.
 
16.
Lahteenmaki PM, Arola M, Suominen J, et al. Male reproductive health after childhood cancer. Acta Paediatr 2008; 97: 935-942.
 
17.
Lahteenmaki PM, Toppari J, Ruokonen A, et al. Low serum inhibin B concentrations in male survivors of childhood malignancy. Eur J Cancer 1999; 35: 612-619.
 
18.
Cicognani A, Cacciari E, Pasini A, et al. Low serum inhibin B levels as a marker of testicular damage after treatment for a childhood malignancy. Eur J Pediatr 2000; 159: 103-107.
 
19.
Wallace EM, Groome NP, Riley SC, et al. Effects of chemotherapy-induced testicular damage on inhibin, gonadotropin, and testosterone secretion: a prospective longitudinal study. J Clin Endocrinol Metab 1997; 82: 3111-3115.
 
20.
van Dorp W, van der Geest IM, Laven JS, et al. Gonadal function recovery in very long-term male survivors of childhood cancer. Eur J Cancer 2013; 49: 1280-1286.
 
21.
van Casteren NJ, van der Linden GH, Hakvoort-Cammel FG, et al. Effect of childhood cancer treatment on fertility markers in adult male long-term survivors. Pediatr Blood Cancer 2009; 52: 108-112.
 
22.
Brignardello E, Felicetti F, Castiglione A, et al. Endocrine health conditions in adult survivors of childhood cancer: the need for specialized adult-focused follow-up clinics. Eur J Endocrinol 2013; 168: 465-472.
 
23.
Laporte S, Couto-Silva AC, Trabado S, et al. Inhibin B and anti-Mullerian hormone as markers of gonadal function after hematopoietic cell transplantation during childhood. BMC Pediatrics 2011; 11: 20.
 
24.
Anserini P, Chiodi S, Spinelli S, et al. Gonadal function post transplantation. Semen analysis following allogeneic bone marrow transplantation. Additional data for evidence-based counselling. Bone Marrow Transplant 2002; 3: 447-451.
 
25.
van Dorp W, van Beek RD, Laven JS, et al. Long-term endocrine side effects of childhood Hodgkin’s lymphoma treatment: a review. Hum Reprod 2012; 18: 12-28.
 
26.
Ben Arush MW, Solt I, Lightman A, et al. Male gonadal function in survivors of childhood Hodgkin and non-Hodgkin lymphoma. Ped Hematol Oncol 2000; 17: 239-245.
 
27.
Relander T, Cavallin-Stahl E, Garwicz S, et al. Gonadal and sexual function in men treated for childhood cancer. Med Ped Oncol 2000; 35: 52-63.
 
28.
Sieniawski M, Reineke T, Nogova L, et al. Fertility in male patients with advanced Hodgkin lymphoma treated with BEACOPP: a report of the German Hodgkin Study Group (GHSG). Blood 2008; 111: 71-76.
 
29.
Behringer K, Mueller H, Goergen H, et al. Gonadal function and fertility in survivors after Hodgkin lymphoma treatment within the German Hodgkin Study Group HD13 to HD15 trials. J Clin Oncol 2013 10; 31: 231-239.
 
30.
Schmiegelow M, Lassen S, Poulsen HS, et al. Gonadal status in male survivors following childhood brain tumors. J Clin Endocrin Metabol 2001; 86: 2446-2452.
 
31.
Bordallo MA, Guimarães MM, Pessoa CH, et al. Decreased serum inhibin B/FSH ratio as a marker of Sertoli cell function in male survivors after chemotherapy in childhood and adolescence. J Ped Endocrin Metabol 2004; 17: 879-887.
 
32.
Aubier F, Flamant F, Brauner R, et al. Male gonadal function after chemotherapy for solid tumors in childhood. J Clin Oncol 1989; 7: 304-309.
 
33.
Meistrich ML, Wilson G, Brown BW, et al. Impact of cyclophosphamide on long-term reduction in sperm count in men treated with combination chemotherapy for Ewing and soft tissue sarcomas. Cancer 1992; 70: 2703-2712.
 
34.
Muller J. Impact of cancer therapy on the reproductive axis. Horm Res 2003; 59 (suppl 1): 12-20.
 
35.
Servitzoglou M, De Vathaire F, Oberlin O, et al. Dose-Effect Relationship of Alkylating Agents on Testicular Function in Male Survivors of Childhood Lymphoma. Pediatr Hematol Oncol 2015; 32: 613-623.
 
36.
Romerius P, Ståhl O, Moëll C, et al. Hypogonadism risk in men treated for childhood cancer. J Clin Endocrinol Metab 2009; 94: 4180-4186.
 
37.
Hobbie WL, Ginsberg JP, Ogle SK, et al. Fertility in males treated for Hodgkin’s disease with COPP/ABV hybrid. Pediatr Blood Cancer 2005; 44: 193-196.
 
38.
Soriano-Guillen L, Munoz–Calvo MT, Pozo-Roman J, et al. Changes in gonadal function in post-pubertal male survivors of acute lymphoblastic leukemia and Hodgkin’s disease. An Esp Pediatr 2000; 53: 318-323.
 
Journals System - logo
Scroll to top