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Aspects of hypogonadism in oncological patients receiving antitumor treatment. Literature review

https://doi.org/10.17650/1726-9776-2025-21-1-119-125

Abstract

Recent development of anticancer drug therapy and the improvement of surgical interventions have led to better oncological treatment outcomes for most patients. The introduction of targeted therapy and immuno-oncological agents into clinical practice has allowed previously incurable diseases to be transformed into chronic conditions. While focusing solely on the effectiveness of therapy, many practicing oncologists often pay little attention to another aspect – toxicity. Hypogonadism is a relatively common adverse event (AE) in men undergoing anticancer treatment. The symptoms of this AE (asthenia, erectile dysfunction, mood variability) are often mistaken for complications of drug therapy. Both chemotherapy (CT) and targeted therapy, as well as immunotherapy, can lead to hypogonadism. According to various authors, platinum-based agents can cause the development of hypogonadism in 50 % of cases among young men. Oxaliplatin-containing regimens may result in a decrease in sperm concentration following adjuvant CT for colorectal cancer. Germ cell tumors of the testis, which have high sensitivity to cisplatin-based CT, are among the most treatable malignant neoplasms, even with metastatic processes. The first stage of treatment for germ cell tumors is orchiectomy, which in itself contributes to the development of hypogonadism. Furthermore, when undergoing CT, the risk of this AE increases significantly, up to 50 % in some publications. Considering that this condition affects men of reproductive age with a very high life expectancy, careful monitoring of total testosterone levels is necessary. Uncorrected hypogonadism can lead to various late AEs: obesity, metabolic syndrome, cardiovascular pathology, and osteopenia.

This literature review examines various aspects of hypogonadism in men receiving anticancer treatment and its impact on the development of late complications.

About the Authors

M. E. Abramov
N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia
Russian Federation

24 Kashirskoe Shosse, Moscow 115522


Competing Interests:

The authors declare no conflict of interest



E. R. Israelyan
N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia
Russian Federation

24 Kashirskoe Shosse, Moscow 115522


Competing Interests:

The authors declare no conflict of interest



A. S. Tsareva
N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia
Russian Federation

24 Kashirskoe Shosse, Moscow 115522


Competing Interests:

The authors declare no conflict of interest



A. A. Rumyantsev
N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia
Russian Federation

24 Kashirskoe Shosse, Moscow 115522


Competing Interests:

The authors declare no conflict of interest



K. A. Firsov
N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia
Russian Federation

Konstantin Andreevich Firsov

24 Kashirskoe Shosse, Moscow 115522


Competing Interests:

The authors declare no conflict of interest



V. B. Matveev
N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia
Russian Federation

24 Kashirskoe Shosse, Moscow 115522


Competing Interests:

The authors declare no conflict of interest



References

1. Corona G., Goulis D.G., Huhtaniemi I. et al. European Academy of Andrology (EAA) guidelines on investigation, treatment and monitoring of functional hypogonadism in males. Andrology 2020;8(5):970–87. DOI: 10.1111/andr.12770

2. Bhasin S., Brito J.P., Cunningham G.R. et al. Testosterone therapy in men with hypogonadism: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 2018;103(5):1715–44. DOI: 10.1210/jc.2018-00229

3. Seftel A.D., Kathrins M., Niederberger C. Critical update of the 2010 endocrine society clinical practice guidelines for male hypogonadism: a systematic analysis. Mayo Clin Proc 2015;90(8):1104–15. DOI: 10.1016/j.mayocp.2015.06.002

4. Afshar M., Patel H.R.H., Jain A. et al. Chronic tyrosine kinase inhibitor (TKI) use in metastatic renal cell carcinoma (mRCC): can this lead to the adverse effect of hypogonadism? Expert Rev Anticancer Ther 2019;19(6):529–32. DOI: 10.1080/14737140.2019.1609355

5. Bastin J., Werbrouck E., Verbiest A. et al. Prospective evaluation of hypogonadism in male metastatic renal cell carcinoma patients treated with targeted therapies. Acta Clin Belg 2019;74(3):169–79. DOI: 10.1080/17843286.2018.1476115

6. Volta A.D., Delbarba A., Valcamonico F. et al. Gonadal function in male patients with metastatic renal cell cancer treated with sunitinib. In Vivo 2023;37(1):410–6. DOI: 10.21873/invivo.13093

7. Ralla B., Magheli A., Wolff I. et al. Prevalence of late-onset hypogonadism in men with localized and metastatic renal cell carcinoma. Urol Int 2016;98(2):191–7. DOI: 10.1159/000450652

8. Weickhardt A.J., Doebele R.C., Purcell W.T. et al. Symptomatic reduction in free testosterone levels secondary to crizotinib use in male cancer patients. Cancer 2013;119(13):2383–90. DOI: 10.1002/cncr.28089

9. Albarel F., Gaudy C., Castinetti F. et al. Long-term follow-up of ipilimumab-induced hypophysitis, a common adverse event of the anti-CTLA-4 antibody in melanoma. Eur J Endocrinol 2015;172(2):195–204. DOI: 10.1530/EJE-14-0845

10. Kassi E., Angelousi A., Asonitis N. et al. Endocrine-related adverse events associated with immune-checkpoint inhibitors in patients with melanoma. Cancer Med 2019;8(15):6585–94. DOI: 10.1002/cam4.2533

11. Ryder M., Callahan M., Postow M.A. et al. Endocrine-related adverse events following ipilimumab in patients with advanced melanoma: a comprehensive retrospective review from a single institution. Endocr Relat Cancer 2014;21(2):371–81. DOI: 10.1530/ERC-13-0499

12. Peters M., Pearlman A., Terry W. et al. Testosterone deficiency in men receiving immunotherapy for malignant melanoma. Oncotarget 2021;12(3):199–208. DOI: 10.18632/oncotarget.27876

13. Faje A.T., Sullivan R., Lawrence D. et al. Ipilimumab-induced hypophysitis: a detailed longitudinal analysis in a large cohort of patients with metastatic melanoma. J Clin Endocrinol Metab 2014;99(11):4078–85. DOI: 10.1210/jc.2014-2306

14. Brunet-Possenti F., Opsomer M.A., Gomez L. et al. Immune checkpoint inhibitors-related orchitis. Ann Oncol 2017;28(4):906–7. DOI: 10.1093/annonc/mdw696

15. Fleishman S.B., Khan H., Homel P. et al. Testosterone levels and quality of life in diverse male patients with cancers unrelated to androgens. J Clin Oncol 2010;28(34):5054–60. DOI: 10.1200/JCO.2010.30.3818

16. Howell S., Shalet S. Gonadal damage from chemotherapy and radiotherapy. Endocrinol Metab Clin North Am 1998;27(4):927–43. DOI: 10.1016/S0889-8529(05)70048-7

17. Falk P., Severin M., Berglund Å. et al. Sex hormones and sperm parameters after adjuvant oxaliplatin-based treatment for colorectal cancer. Cancer Treat Res Commun 2022;31:100517. DOI: 10.1016/j.ctarc.2022.100517

18. Germ cell tumors in men. Clinical guidelines. Association of Oncologists of Russia. Available at: https://oncology-association.ru/wp-content/uploads/2020/09/germinogennye_opuholi-2.pdf (In Russ.).

19. Beyer J., Collette L., Sauve N. et al. Survival and new prognosticators in metastatic seminoma: results from the IGCCCG-Update Consortium. J Clin Oncol 2021;39(14):1554–62. DOI: 10.1200/JCO.20.03292

20. Gillessen S., Sauve N., Collette L. et al. Predicting outcomes in men with metastatic nonseminomatous germ cell tumors (NSGCT): results from the IGCCCG Update Consortium. J Clin Oncol 2021;39(14):1563–74. DOI: 10.1200/JCO.20.03296

21. Williams D., Birch R., Einhorn L. et al. Treatment of disseminated germ-cell tumors with cisplatin, bleomycin, and either vinblastine or etoposide. N Engl J Med 1987;316:1435–40. DOI: 10.1056/NEJM198706043162302

22. Nichols C.R., Catalano P.J., Crawford E.D. et al. Randomized comparison of cisplatin and etoposide and either bleomycin or ifosfamide in treatment of advanced disseminated germ cell tumors: an Eastern Cooperative Oncology Group, Southwest Oncology Group, and Cancer and Leukemia Group B Study. J Clin Oncol 1998;16(4):1287–93. DOI: 10.1200/JCO.1998.16.4.1287

23. Christian J.A., Huddart R.A., Norman A. et al. Intensive induction chemotherapy with CBOP/BEP in patients with poor prognosis germ cell tumors. J Clin Oncol 2003;21(5):871–7. DOI: 10.1200/JCO.2003.05.155

24. La Vignera S., Cannarella R., Duca Y. et al. Hypogonadism and sexual dysfunction in testicular tumor survivors: a systematic review. Front Endocrinol 2019;10:264. DOI: 10.3389/fendo.2019.00264

25. Nord C., Bjøro T., Ellingsen D. et al. Gonadal hormones in long-term survivors 10 years after treatment for unilateral testicular cancer. Eur Urol 2003;44(3):322–8 DOI: 10.1016/s0302-2838(03)00263-x

26. Huddart R.A., Norman A., Moynihan C. et al. Fertility, gonadal and sexual function in survivors of testicular cancer. Br J Cancer 2005;93(2):200–7. DOI: 10.1038/sj.bjc.6602677

27. Khanal N., Ahmed S., Kalra M. et al. The effects of hypogonadism on quality of life in survivors of germ cell tumors treated with surgery alone versus surgery plus platinum-based chemotherapy. Support Care Cancer 2020;28(7):3165–70. DOI: 10.1007/s00520-019-05117-0

28. Brydøy M., Fosså S.D., Klepp O. et al. Paternity following treatment for testicular cancer. J Natl Cancer Inst 2005;97(21):1580–8. DOI: 10.1093/jnci/dji339

29. Albrecht P.W. Fertility after chemotherapy for testicular germ cell cancer. Fertil Steril 1997;68(1):1–5. DOI: 10.1016/s0015-0282(97)81465-3

30. Howell S.J., Radford J.A., Ryder W.D., Shalet S.M. Testicular function after cytotoxic chemotherapy: evidence of Leydig cell insufficiency. J Clin Oncol 1999;17(5):1493–98. DOI: 10.1200/JCO.1999.17.5.1493

31. Takai Y., Naito S., Kanno H. et al. Body composition changes following chemotherapy for testicular germ cell tumor: obesity is the long-term problem. Asian J Androl 2022;24(5):458–62. DOI: 10.4103/aja202195

32. Nuver J., Smit A.J., Wolffenbuttel B.H. et al. The metabolic syndrome and disturbances in hormone levels in long-term survivors of disseminated testicular cancer. J Clin Oncol 2005;23:3718–25. DOI: 10.1200/JCO.2005.02.176

33. Willemse P.M., Burggraaf J., Hamdy N.A. et al. Prevalence of the metabolic syndrome and cardiovascular disease risk in chemotherapy-treated testicular germ cell tumour survivors. Br J Cancer 2013;109:60–7. DOI: 10.1038/bjc.2013.226

34. Zaid M.A., Gathirua-Mwangi W.G., Fung C. et al. Clinical and genetic risk factors for adverse metabolic outcomes in North American testicular cancer survivors. J Nat Compr Canc Netw 2018;16:257–65. DOI: 10.6004/jnccn.2017.7046

35. Pandey P., Dabkara D., Ganguly S. et al. Early metabolic syndrome in testicular germ cell tumors: A prospective study from India. J Clin Oncol 2022;40(16):e17010. DOI: 10.1200/JCO.2022.40.16_suppl.e17010

36. Poniatowska G., Michalski W., Kucharz J. et al. What is the damage? Testicular germ cell tumour survivors deficient in testosterone at risk of metabolic syndrome and a need for medical intervention. Med Oncol 2020;37(9):82. DOI: 10.1007/s12032-020-01407-4

37. Vrouwe J., Hennus P., Hamdy N. et al. Risk of osteoporosis in testicular germ cell tumour survivors: a systematic review of the literature. BJUI Compass 2023;4(1):24–43. DOI: 10.1002/bco2.183

38. Kerns S.L., Fung C., Monahan P.O. et al.; Platinum Study Group. Cumulative burden of morbidity among testicular cancer survivors after standard cisplatin-based chemotherapy: a multi-institutional study. J Clin Oncol 2018;36:1505–12. DOI: 10.1200/JCO.2017.77.0735

39. Huddart R.A., Norman A., Shahidi M. et al. Cardiovascular disease as a long-term complication of treatment for testicular cancer. J Clin Oncol 2003;21:1513–23. DOI: 10.1200/JCO.2003.04.173

40. Meinardi M.T., Gietema J.A., van der Graaf W.T. et al. Cardiovascular morbidity in long-term survivors of metastatic testicular cancer. J Clin Oncol 2000;18:1725–32. DOI: 10.1200/JCO.2000.18.8.1725

41. Haugnes H.S., Wethal T., Aass N. et al. Cardiovascular risk factors and morbidity in long-term survivors of testicular cancer: a 20-year follow-up study. J Clin Oncol 2010;28:4649–57. DOI: 10.1200/JCO.2010.29.9362

42. Bandak M., Lauritsen J., Johansen C. Sexual function in a nationwide cohort of 2,260 survivors of testicular cancer after 17 years of followup. J Urol 2018;200(4):794–800. DOI: 10.1016/j.juro.2018.04.077


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For citations:


Abramov M.E., Israelyan E.R., Tsareva A.S., Rumyantsev A.A., Firsov K.A., Matveev V.B. Aspects of hypogonadism in oncological patients receiving antitumor treatment. Literature review. Cancer Urology. 2025;21(1):119-125. (In Russ.) https://doi.org/10.17650/1726-9776-2025-21-1-119-125

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