Abstract
Purpose
To evaluate the prevalence of gonadal dysfunction and the associated risk factors in a cohort of male childhood cancer survivors (CCS).
Methods
Gonadal function was evaluated measuring FSH, LH, inhibin B and total testosterone levels. Patients with total testosterone <3 ng/dl were considered to have hypogonadism. Patients with FSH >10 UI/l and inhibin B <100 pg/ml were considered to have spermatogenesis damage (SD). To assess the impact of risk factors, we estimated crude and adjusted OR performing logistic regression models.
Results
One hundred and ninety-nine male CCS were enrolled; the median follow-up time was 14.01 years. SD was diagnosed in 68 patients, 16 CCS had primary hypogonadism, and 13 had central hypogonadism. The prevalence of gonadal dysfunction (SD or primary hypogonadism) was 45 %, similar in the three considered periods of pediatric cancer diagnosis (1985–1989, 1990–1999, >2000). The adjusted risk of gonadal dysfunction was higher in patients treated with radiotherapy (OR = 8.72; 95 % CI 3.94–19.30) and in those exposed to both alkylating and platinum-derived agents (OR = 9.22; 95 % CI 2.17–39.23). Sarcomas were the cancer diagnosis associated with the higher risk of gonadal dysfunction (OR = 3.69; 95 % CI 1.11–12.22). An extremely high rate of gonadal dysfunction was detected in patients who underwent hematopoietic stem cell transplantation and/or total body irradiation.
Conclusions
Gonadal dysfunction still remains a significant late effect of anticancer therapies; thus, it is mandatory to inform patients (and parents) about this risk, and semen cryopreservation should be offered to all boys who are able to produce semen.
Similar content being viewed by others
References
Anserini P, Chiodi S, Spinelli S, Costa M, Conte N, Copello F, Bacigalupo A (2002) Semen analysis following allogeneic bone marrow transplantation. Additional data for evidence-based counselling. Bone Marrow Transplant 30:447–451
Armstrong GT, Stovall M, Robison LL (2010) Long-term effects of radiation exposure among adult survivors of childhood cancer: results from the childhood cancer survivor study. Radiat Res 174:840–850
Brignardello E, Felicetti F, Castiglione A, Chiabotto P, Corrias A, Fagioli G, Ciccone G, Boccuzzi G (2013) Endocrine health conditions in adult survivors of childhood cancer: the need for specialized adult-focused follow-up clinic. Eur J Endocrinol 168:465–472
Centola GM, Keller JW, Henzler M, Rubin P (1994) Effect of low-dose testicular irradiation on sperm count and fertility in patients with testicular seminoma. J Androl 15:608–613
Felicetti F, Manicone R, Corrias A, Manieri C, Biasin E, Bini I, Boccuzzi G, Brignardello E (2011) Endocrine late effects after total body irradiation in patients who received hematopoietic cell transplantation during childhood: a retrospective study from a single institution. J Cancer Res Clin Oncol 137:1343–1348
Green DM, Liu W, Kutteh WH, Ke RW, Shelton KC, Sklar CA, Chemaitilly W, Pui CH, Klosky JL, Spunt SL, Metzger ML, Srivastava D, Ness KK, Robison LL, Hudson MM (2014) Cumulative alkylating agent exposure and semen parameters in adult survivors of childhood cancer: a report from the St Jude Lifetime Cohort Study. Lancet Oncol 15:1215–1223
Holoch P, Wald M (2011) Current options for preservation of fertility in the male. Fertil Steril 96:286–290
Jahnukainen K, Ehmcke J, Hou M, Schlatt S (2011) Testicular function and fertility preservation in male cancer patients. Best Pract Res Clin Endocrinol Metab 25:287–302
Joshi S, Savani BN, Chow EJ, Gilleece MH, Halter J, Jacobsohn D, Pidala J, Quinn GP, Cahn JY, Jakubowski AA, Kamani NR, Lazarus HM, Rizzo JD, Schouten HC, Socie G, Stratton P, Sorror ML, Warwick AB, Wingard JR, Loren AW, Majhail NS (2014) Clinical guide to fertility preservation in hematopoietic cell transplant recipients. Bone Marrow Transplant 49:477–484
Kenney LB, Cohen LE, Shnorhavorian M, Metzger ML, Lockart B, Hijiya N, Duffey-Lind E, Constine L, Green D, Meacham L (2012) Male reproductive health after childhood, adolescent, and young adult cancers: a report from the Children’s Oncology Group. J Clin Oncol 30:3408–3416
Lee SH, Shin CH (2013) Reduced male fertility in childhood cancer survivors. Ann Pediatr Endocrinol Metab 18:168–172
Loren AW, Mangu PB, Beck LN, Brennan L, Magdalinski AJ, Partridge AH, Quinn G, Wallace WH, Oktay K, American Society of Clinical Oncology (2013) Fertility preservation for patients with cancer: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol 31:2500–2510
Meistrich ML (2013) Effects of chemotherapy and radiotherapy on spermatogenesis in humans. Fertil Steril 100:1180–1186
National Cancer Institute (2015) SEER—Surveillance, Epidemiology, and End Results Program—Cancer Statistics. http://seer.cancer.gov. Accessed 27 Sept 2015
Oeffinger KC, Mertens AC, Sklar CA, Kawashima T, Hudson MM, Meadows AT, Friedman DL, Marina N, Hobbie W, Kadan-Lottick NS, Schwartz CL, Leisenring W, Robison LL (2006) Childhood Cancer Survivor Study. Chronic health conditions in adult survivors of childhood cancer. N Engl J Med 355:1572–1582
Parry C, Kent EE, Mariotto AB, Alfano CM, Rowland KH (2005) Cancer survivors: a booming population. Cancer Epidemiol Biomarkers Prev 20:1996–2005
Rivkees SA, Crawford JD (1988) The relationship of gonadal activity and chemotherapy-induced gonadal damage. JAMA 259:2123–2125
Romerius P, Ståhl O, Moëll C, Relander T, Cavallin-Ståhl E, Wiebe T, Giwercman YL, Giwercman A (2009) Hypogonadism risk in men treated for childhood cancer. J Clin Endocrinol Metab 94:4180–4186
Rowley MJ, Leach DR, Warner GA, Heller CG (1974) Effect of graded doses of ionizing radiation on the human testis. Radiat Res 59:665–678
Shalet SM, Tsatsoulis A, Whitehead E, Read G (1989) Vulnerability of the human Leydig cell to radiation damage is dependent upon age. J Endocrinol 120:161–165
Tromp K, Claessens JJ, Knijnenburg SL, van der Pal HJ, van Leeuwen FE, Caron HN, Beerendonk CC, Kremer LC (2011) Reproductive status in adult male long-term survivors of childhood cancer. Hum Reprod 26:1775–1783
van Casteren NJ, van der Linden GHM, Hakvoort-Cammel FGAJ, Hahlen K, Dohle GR, van den Heuvel-Eibrink MM (2009) Effect of childhood cancer treatment on fertility markers in adult male long-term survivors. Pediatr Blood Cancer 52:108–112
Wallace WH (2011) Oncofertility and preservation of reproductive capacity in children and young adults. Cancer 117:2301–2310
Wyns C, Curaba M, Vanabelle B, Van Langendonckt A, Donnez J (2010) Options for fertility preservation in prepubertal boys. Hum Reprod Update 16:312–328
Acknowledgments
The authors would like to acknowledge UGI (Unione Genitori Italiani contro il tumore dei bambini), for the ongoing support to clinical and research activities of the Transition Unit for Childhood Cancer Survivors.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Ethical approval
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
Informed consent
For this type of study, formal consent is not required.
Rights and permissions
About this article
Cite this article
Brignardello, E., Felicetti, F., Castiglione, A. et al. Gonadal status in long-term male survivors of childhood cancer. J Cancer Res Clin Oncol 142, 1127–1132 (2016). https://doi.org/10.1007/s00432-016-2124-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00432-016-2124-5