agxАндрология и генитальная хирургияAndrology and Genital Surgery2070-97812412-890210.17650/2070-9781-2022-23-4-26-35agx-613Research ArticleОБЗОРНАЯ СТАТЬЯREVIEWЭволюция представлений о роли тестостерона при раке предстательной железы. Обзор литературыEvolution of the views on the role of testosterone in prostate cancer. Literature reviewhttps://orcid.org/0000-0002-1017-7470АхвледианиН. Д.AkhvledianiN. D.

Ника Джумберович Ахвледиани

Кафедра урологии

127473 Москва, ул. Делегатская, 20, стр. 1

Nika Dzhumberovich Akhvlediani

Department of Urology

Bld. 1, 20 Delegatskaya St., Moscow 127473

nikandro@mail.ruhttps://orcid.org/0000-0001-6654-9280БабаевМ. У.BabaevM. U.

Кафедра урологии

127473 Москва, ул. Делегатская, 20, стр. 1

Department of Urology

Bld. 1, 20 Delegatskaya St., Moscow 127473

СоловьевВ. В.SolovyevV. V.

117545 Москва, ул. Подольских курсантов, 2, корп. 2 

Bld. 2, 2 Podolskikh Kursantov St., Moscow 117545

ФГБОУ ВО «Московский государственный медико-стоматологический университет им. А.И. Евдокимова» Минздрава РоссииРоссияA.I. Evdokimov Moscow State University of Medicine and Dentistry, Ministry of Health of RussiaRussian FederationГБУЗ «Городская поликлиника № 170 Департамента здравоохранения города Москвы»РоссияCity Polyclinic No. 170, Moscow Healthcare DepartmentRussian Federation2022080120232342635Copyright © Ахвледиани Н.Д., Бабаев М.У., Соловьев В.В., 20232023Ахвледиани Н.Д., Бабаев М.У., Соловьев В.В.Akhvlediani N.D., Babaev M.U., Solovyev V.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://agx.elpub.ru/jour/article/view/613Введение

Введение. Рак предстательной железы – одно из самых частых онкологических заболеваний у мужчин. Представления о роли основного мужского гормона – тестостерона – в генезе карциномы предстательной железы кардинально менялись за последние два с лишним века.  

Цель исследования – проанализировать эволюцию взглядов на взаимосвязь тестостерона и рака предстательной железы и оценить ее влияние на организацию медицинской помощи.  

Материалы и методы

Материалы и методы. Поиск публикаций осуществлялся в Национальной медицинской библиотеке США и Центральной научной медицинской библиотеке Российской Федерации по ключевым словам: рак предстательной железы, тестостерон. Учитывались только оригинальные публикации и метаанализы. В итоге было отобрано 59 публикаций и проведен их описательный анализ.  

Результаты

Результаты. Представлены сведения о сомнительности отрицательной роли тестостерона в канцерогенезе рака предстательной железы ввиду малого числа наблюдений и многочисленных методологических дефектов проведенных исследований. Обозначена доказательность теории андрогенного насыщения при карциономе предстательной железы, которая основана на работах с достаточным количеством наблюдений. Описаны исследования, подтверждающие отсутствие канцерогенного влияния андрогензаместительной терапии у здоровых индивидов и прогрессии опухолевого процесса на фоне назначения тестостерона после лечения онкологического процесса. Более того, приведены сведения о применении указанного гормона при лечении кастрационно-резистентной формы карциномы предстательной железы.  

Заключение

Заключение. С течением времени появляется все больше данных, которые подтверждают протективную роль тестостерона в отношении развития и даже при лечении рака предстательной железы. В связи с этим возникает перспектива глобальной трансформации организации медицинской помощи в вопросах тактики ведения больных карциномой предстательной железы, а также в целом мужчин старших возрастных групп. Очевидной остается необходимость проведения новых более качественных исследований по указанному вопросу. 

Background

Background. Prostate cancer is one of the most common cancers in men. The views on the role of the main male hormone, testosterone, in the genesis of prostate carcinoma has changed dramatically over the last two centuries.  

Aim

Aim. To study the evolution of views on the relationship between testosterone and prostate cancer and to assess their impact on the organization of medical care.  

Materials and methods

Materials and methods. Publications were searched in the National Library of Medicine of the United States and the Central Scientific Medical Library of the Russian Federation using the keywords: prostate cancer, testosterone. Only original publications and meta-analyses were considered. As a result, 59 publications were selected and their descriptive analysis was performed.  

Results

Results. The information aboutthe doubtfulness ofthe negative role oftestosterone in genesis of prostate cancer is presented, taking into account the small number of observations and numerous methodological defects of the studies. The evidence for the theory of androgenic saturation in prostate carcinoma is outlined, which is based on publications with a sufficient number of publications. Studies confirming the absence of a carcinogenic effect of androgen replacement therapy in healthy individuals and progression of the tumor process on testosterone administration after treatment of the cancer process are described. Moreover, there is information on the use of this hormone in the treatment of castration-resistant prostate carcinoma.  

Conclusion

Conclusion. Over time, there is increasing evidence for the protective role of testosterone in the development and even treatment of prostate cancer. This raises the prospect of a global transformation in the organization of medical care in the management of patients with prostatic carcinoma, as well as older men in general. There is a clear need for new and better research on this issue. 

рак предстательной железытестостеронобзорprostate cancertestosteronereviewReferencesRider J.R., Wilson K.M., Sinnott J.A. et al. Ejaculation frequency and risk of prostate cancer: updated results with an additional decade of follow-up. Eur Urol 2016;70(6):974–82. DOI: 10.1016/j.eururo.2016.03.027Rider J.R., Wilson K.M., Sinnott J.A. et al. Ejaculation frequency and risk of prostate cancer: updated results with an additional decade of follow-up. Eur Urol 2016;70(6):974–82. DOI: 10.1016/j.eururo.2016.03.027Злокачественные новообразования в России в 2017 году (заболеваемость и смертность). Под. ред. А.Д. Каприна, В.В. Старинского, Г.В. Петрова. М.: МНИОИ им. П.А. Герцена – филиал ФГБУ «НМИЦ радиологии» Минздрава России, 2018. 250 с.Malignant neoplasms in Russia in 2017 (morbidity and mortality). Ed. by A.D. Kaprin, V.V. Starinskiy, G.V. Moscow: MNIOI im. P.A. Gertsena – filial FGBU “NMITS radiologii” Minzdrava Rossii, 2018. 250 p. (In Russ.).Аляев Ю.Г., Асламазов Э.Г., Ахвледиани Н.Д. 145 лет урологической клинике имени Р.М. Фронштейна. М.: Дипак, 2012. 240 с.Alyaev Y.G., Aslamazov E.G., Akhvlediani N.D. 145 years of urological clinic named after R.M. Fronstein. Moscow: Dipak, 2012. 240 p. (In Russ.).Huggins C., Hodges C.V. Studies on prostatic cancer, I: the effect of castration, of estrogen and of androgen injection on serum phos phatases in metastatic carcinoma of the prostate. Cancer Res 1941;1(4):293–7.Huggins C., Hodges C.V. Studies on prostatic cancer, I: the effect of castration, of estrogen and of androgen injection on serum phos phatases in metastatic carcinoma of the prostate. Cancer Res 1941;1(4):293–7.Huggins C., Stevens R.E., Hodges C.V. Studies on prostatic cancer. II. The effects of castration on advanced carcinoma of the prostate gland. Arch Surg 1941;43(2):209–23. DOI: 10.1001/archsurg.1941.01210140043004Huggins C., Stevens R.E., Hodges C.V. Studies on prostatic cancer. II. The effects of castration on advanced carcinoma of the prostate gland. Arch Surg 1941;43(2):209–23. DOI: 10.1001/archsurg.1941.01210140043004Morgentaler A., Traish A. The history of testosterone and the evolution of its therapeutic potential. Sex Med Rev 2020;8(2):286–96. DOI: 10.1016/j.sxmr.2018.03.002Morgentaler A., Traish A. The history of testosterone and the evolution of its therapeutic potential. Sex Med Rev 2020;8(2):286–96. DOI: 10.1016/j.sxmr.2018.03.002Prout G.R. Jr., Brewer W.R. Response of men with advanced prostatic carcinoma to exogenous administration of testosterone. Cancer 1967;20(11):1871–8. DOI: 10.1002/1097-0142(196711)20:11<1871::aidcncr2820201112>3.0.co;2-dProut G.R. Jr., Brewer W.R. Response of men with advanced prostatic carcinoma to exogenous administration of testosterone. Cancer 1967;20(11):1871–8. DOI: 10.1002/1097-0142(196711)20:11<1871::aidcncr2820201112>3.0.co;2-dFowler J.E. Jr., Whitmore W.F. Jr. The response of metastatic adenocarcinoma of the prostate to exogenous testosterone. J Urol 1981;126(3):372–5. DOI: 10.1016/s0022-5347(17)54531-0Fowler J.E. Jr., Whitmore W.F. Jr. The response of metastatic adenocarcinoma of the prostate to exogenous testosterone. J Urol 1981;126(3):372–5. DOI: 10.1016/s0022-5347(17)54531-0Stamey T.A., Yang N., Hay A.R. et al. Prostate-specific antigen as a serum marker for adenocarcinoma of the prostate. N Engl J Med 1987;317(15):909–16. DOI: 10.1056/nejm198710083171501Stamey T.A., Yang N., Hay A.R. et al. Prostate-specific antigen as a serum marker for adenocarcinoma of the prostate. N Engl J Med 1987;317(15):909–16. DOI: 10.1056/nejm198710083171501Morgentaler A., Bruning C.O. 3rd, DeWolf W.C. Occult prostate cancer in men with low serum testosterone levels. JAMA 1996;276(23):1904–6. DOI: 0.1001/jama.1996.03540230054035Morgentaler A., Bruning C.O. 3rd, DeWolf W.C. Occult prostate cancer in men with low serum testosterone levels. JAMA 1996;276(23):1904–6. DOI: 0.1001/jama.1996.03540230054035Morgentaler A., Rhoden E.L. Prevalence of prostate cancer among hypogonadal men with prostate-specific antigen levels of 4.0 ng/mL or less. Urology 2006;68(6):1263–7. DOI: 10.1016/j.urology.2006.08.1058Morgentaler A., Rhoden E.L. Prevalence of prostate cancer among hypogonadal men with prostate-specific antigen levels of 4.0 ng/mL or less. Urology 2006;68(6):1263–7. DOI: 10.1016/j.urology.2006.08.1058Rhoden E.L., Morgentaler A. Risks of testosterone-replacement therapy and recommendations for monitoring. N Engl J Med 2004;350(5):482–92. DOI: 10.1056/NEJMra022251Rhoden E.L., Morgentaler A. Risks of testosterone-replacement therapy and recommendations for monitoring. N Engl J Med 2004;350(5):482–92. DOI: 10.1056/NEJMra022251Endogenous Hormones and Prostate Cancer Collaborative Group, Roddam A.W., Allen N.E., Appleby P., Key T.J. Endogenous sex hormones and prostate cancer: a collaborative analysis of 18 prospective studies. J Natl Cancer Inst 2008;100(3):170–83. DOI: 10.1093/jnci/djm323.Endogenous Hormones and Prostate Cancer Collaborative Group, Roddam A.W., Allen N.E., Appleby P., Key T.J. Endogenous sex hormones and prostate cancer: a collaborative analysis of 18 prospective studies. J Natl Cancer Inst 2008;100(3):170–83. DOI: 10.1093/jnci/djm323.Morgentaler A. Testosterone and prostate cancer: an historical perspective on a modern myth. Eur Urol 2006;50(5):935–9. DOI: 10.1016/j.eururo.2006.06.034Morgentaler A. Testosterone and prostate cancer: an historical perspective on a modern myth. Eur Urol 2006;50(5):935–9. DOI: 10.1016/j.eururo.2006.06.034Morgentaler A., Traish A.M. Shifting the paradigm of testosterone and prostate cancer: the saturation model and the limits of androgen-dependent growth. Eur Urol 2009;55(2):310–20. DOI: 10.1016/j.eururo.2008.09.024Morgentaler A., Traish A.M. Shifting the paradigm of testosterone and prostate cancer: the saturation model and the limits of androgen-dependent growth. Eur Urol 2009;55(2):310–20. DOI: 10.1016/j.eururo.2008.09.024Wright A.S., Douglas R.C., Thomas L.N. et al. Androgen-induced regrowth in the castrated rat ventral prostate: role of 5alphareductase. Endocrinology 1999;140(10):4509–15. DOI: 10.1210/endo.140.10.7039Wright A.S., Douglas R.C., Thomas L.N. et al. Androgen-induced regrowth in the castrated rat ventral prostate: role of 5alphareductase. Endocrinology 1999;140(10):4509–15. DOI: 10.1210/endo.140.10.7039Traish A.M., Muller R.E., Wotiz H.H. A new procedure for the quantitation of nuclear and cytoplasmic androgen receptors. J Biol Chem 1981;256(23):12028–33.Traish A.M., Muller R.E., Wotiz H.H. A new procedure for the quantitation of nuclear and cytoplasmic androgen receptors. J Biol Chem 1981;256(23):12028–33.Traish A.M., Williams D.F., Hoffman N.D., Wotiz H.H. Validation of the exchange assay for the measurement of androgen receptors in human and dog prostates. Prog Clin Biol Res 1988;262:145–60.Traish A.M., Williams D.F., Hoffman N.D., Wotiz H.H. Validation of the exchange assay for the measurement of androgen receptors in human and dog prostates. Prog Clin Biol Res 1988;262:145–60.Marks L.S., Mazer N.A., Mostaghel E. et al. Effect of testosterone replacement therapy on prostate tissue in men with late-onset hypogonadism: a randomized controlled trial. JAMA 2006;296(19):2351–61. DOI: 10.1001/jama.296.19.2351Marks L.S., Mazer N.A., Mostaghel E. et al. Effect of testosterone replacement therapy on prostate tissue in men with late-onset hypogonadism: a randomized controlled trial. JAMA 2006;296(19):2351–61. DOI: 10.1001/jama.296.19.2351Salonia A., Abdollah F., Capitanio U. et al. Serum sex steroids depict a nonlinear u-shaped association with high-risk prostate cancer at radical prostatectomy. Clin Cancer Res 2012;18(13):3648–57. DOI: 10.1158/1078-0432.CCR-11-2799Salonia A., Abdollah F., Capitanio U. et al. Serum sex steroids depict a nonlinear u-shaped association with high-risk prostate cancer at radical prostatectomy. Clin Cancer Res 2012;18(13):3648–57. DOI: 10.1158/1078-0432.CCR-11-2799Miranda E.P., Torres L.O. Late-onset hypogonadism: prostate safety. Andrology 2020;8(6):1606–13. DOI: 10.1111/andr.12772Miranda E.P., Torres L.O. Late-onset hypogonadism: prostate safety. Andrology 2020;8(6):1606–13. DOI: 10.1111/andr.12772Debruyne F.M., Behre H.M., Roehrborn C.G. et al. Testosterone treatment is not associated with increased risk of prostate cancer or worsening of lower urinary tract symptoms: prostate health outcomes in the Registry of Hypogonadism in Men. BJU Int 2017;119(2):216–24. DOI: 10.1111/bju.13578Debruyne F.M., Behre H.M., Roehrborn C.G. et al. Testosterone treatment is not associated with increased risk of prostate cancer or worsening of lower urinary tract symptoms: prostate health outcomes in the Registry of Hypogonadism in Men. BJU Int 2017;119(2):216–24. DOI: 10.1111/bju.13578Elliott J., Kelly S.E., Millar A.C. et al. Testosterone therapy in hypogonadal men: a systematic review and network metaanalysis. BMJ Open 2017;7(11):e015284. DOI: 10.1136/bmjopen-2016-015284Elliott J., Kelly S.E., Millar A.C. et al. Testosterone therapy in hypogonadal men: a systematic review and network metaanalysis. BMJ Open 2017;7(11):e015284. DOI: 10.1136/bmjopen-2016-015284McLaren D., Siemens D.R., Izard J. et al. Clinical practice experience with testosterone treatment in men with testosterone deficiency syndrome. BJU Int 2008;102(9):1142–6. DOI: 10.1111/j.1464-410X.2008.07811.xMcLaren D., Siemens D.R., Izard J. et al. Clinical practice experience with testosterone treatment in men with testosterone deficiency syndrome. BJU Int 2008;102(9):1142–6. DOI: 10.1111/j.1464-410X.2008.07811.xCooper C.S., MacIndoe J.H., Perry P.J. et al. The effect of exogenous testosterone on total and free prostate specific antigen levels in healthy young men. J Urol 1996;156(2 Pt 1):438–41; discussion 441–2. DOI: 10.1097/00005392-199608000-00028Cooper C.S., MacIndoe J.H., Perry P.J. et al. The effect of exogenous testosterone on total and free prostate specific antigen levels in healthy young men. J Urol 1996;156(2 Pt 1):438–41; discussion 441–2. DOI: 10.1097/00005392-199608000-00028Gerstenbluth R.E., Maniam P.N., Corty E.W., Seftel A.D. Prostatespecific antigen changes in hypogonadal men treated with testosterone replacement. J Androl 2002;23(6):922–6.Gerstenbluth R.E., Maniam P.N., Corty E.W., Seftel A.D. Prostatespecific antigen changes in hypogonadal men treated with testosterone replacement. J Androl 2002;23(6):922–6.Morgentaler A., Lipshultz L.I., Bennett R. et al. Testosterone therapy in men with untreated prostate cancer. J Urol 2011;185(4):1256–60. DOI: 10.1016/j.juro.2010.11.084Morgentaler A., Lipshultz L.I., Bennett R. et al. Testosterone therapy in men with untreated prostate cancer. J Urol 2011;185(4):1256–60. DOI: 10.1016/j.juro.2010.11.084Morales A. Effect of testosterone administration to men with prostate cancer is unpredictable: a word of caution and suggestions for a registry. BJU Int 2011;107(9):1369–73. DOI: 10.1111/j.1464-410X.2011.10193.xMorales A. Effect of testosterone administration to men with prostate cancer is unpredictable: a word of caution and suggestions for a registry. BJU Int 2011;107(9):1369–73. DOI: 10.1111/j.1464-410X.2011.10193.xKacker R., Hult M., San Francisco I.F. et al. Can testosterone therapy be offered to men on active surveillance for prostate cancer? Preliminary results. Asian J Androl 2016;18(1):16–20. DOI: 10.4103/1008-682X.160270Kacker R., Hult M., San Francisco I.F. et al. Can testosterone therapy be offered to men on active surveillance for prostate cancer? Preliminary results. Asian J Androl 2016;18(1):16–20. DOI: 10.4103/1008-682X.160270Kaufman J.M., Graydon R.J. Androgen replacement after curative radical prostatectomy for prostate cancer in hypogonadal men. J Urol 2004;172(3):920–2. DOI: 10.1097/01.ju.0000136269.10161.32Kaufman J.M., Graydon R.J. Androgen replacement after curative radical prostatectomy for prostate cancer in hypogonadal men. J Urol 2004;172(3):920–2. DOI: 10.1097/01.ju.0000136269.10161.32Agarwal P.K., Oefelein M.G. Testosterone replacement therapy after primary treatment for prostate cancer. J Urol 2005;173(2):533–6. DOI: 10.1097/01.ju.0000143942.55896.64Agarwal P.K., Oefelein M.G. Testosterone replacement therapy after primary treatment for prostate cancer. J Urol 2005;173(2):533–6. DOI: 10.1097/01.ju.0000143942.55896.64Mulhall J.P., Trost L.W., Brannigan R.E. et al. Evaluation and management of testosterone deficiency: AUA Guideline. J Urol 2018;200(2):423–32. DOI: 10.1016/j.juro.2018.03.115Mulhall J.P., Trost L.W., Brannigan R.E. et al. Evaluation and management of testosterone deficiency: AUA Guideline. J Urol 2018;200(2):423–32. DOI: 10.1016/j.juro.2018.03.115Salonia A., Bettocchi C., Boeri L. et al. European Association of Urology Guidelines on Sexual and Reproductive Health-2021 Update: Male Sexual Dysfunction. Eur Urol 2021;80(3):333–57. DOI: 10.1016/j.eururo.2021.06.007Salonia A., Bettocchi C., Boeri L. et al. European Association of Urology Guidelines on Sexual and Reproductive Health-2021 Update: Male Sexual Dysfunction. Eur Urol 2021;80(3):333–57. DOI: 10.1016/j.eururo.2021.06.007Natale C., Carlos C., Hong J. et al. Testosterone therapy after prostate cancer treatment: a review of literature. Sex Med Rev 2021;9(3):393–405. DOI: 10.1016/j.sxmr.2020.12.003Natale C., Carlos C., Hong J. et al. Testosterone therapy after prostate cancer treatment: a review of literature. Sex Med Rev 2021;9(3):393–405. DOI: 10.1016/j.sxmr.2020.12.003Pastuszak A.W., Pearlman A.M., Lai W.S. et al. Testosterone replacement therapy in patients with prostate cancer after radical prostatectomy. J Urol 2013;190(2):639–44. DOI: 10.1016/j.juro.2013.02.002Pastuszak A.W., Pearlman A.M., Lai W.S. et al. Testosterone replacement therapy in patients with prostate cancer after radical prostatectomy. J Urol 2013;190(2):639–44. DOI: 10.1016/j.juro.2013.02.002Wynia B., Lee T., Taneja S. et al. Testosterone replacement therapy in patients with prostate cancer after prostatectomy: a 5-year single center experience. J Urol 2014;191(4):527. DOI: 10.1016/j.juro.2014.02.1477Wynia B., Lee T., Taneja S. et al. Testosterone replacement therapy in patients with prostate cancer after prostatectomy: a 5-year single center experience. J Urol 2014;191(4):527. DOI: 10.1016/j.juro.2014.02.1477Gray H., Seltzer J., Talbert R.L. Recurrence of prostate cancer in patients receiving testosterone supplementation for hypogonadism. Am J Health Syst Pharm 2015;72(7):536–41. DOI: 10.2146/ajhp140128Gray H., Seltzer J., Talbert R.L. Recurrence of prostate cancer in patients receiving testosterone supplementation for hypogonadism. Am J Health Syst Pharm 2015;72(7):536–41. DOI: 10.2146/ajhp140128Pastuszak A.W., Pearlman A.M., Godoy G. et al. Testosterone replacement therapy in the setting of prostate cancer treated with radiation. Int J Impot Res 2013;25(1):24–8. DOI: 10.1038/ijir.2012.29Pastuszak A.W., Pearlman A.M., Godoy G. et al. Testosterone replacement therapy in the setting of prostate cancer treated with radiation. Int J Impot Res 2013;25(1):24–8. DOI: 10.1038/ijir.2012.29Pastuszak A.W., Khanna A., Badhiwala N. et al. Testosterone therapy after radiation therapy for low, intermediate and high risk prostate cancer. J Urol 2015;194(5):1271–6. DOI: 10.1016/j.juro.2015.05.084Pastuszak A.W., Khanna A., Badhiwala N. et al. Testosterone therapy after radiation therapy for low, intermediate and high risk prostate cancer. J Urol 2015;194(5):1271–6. DOI: 10.1016/j.juro.2015.05.084Kacker R., Hult M., Conners W., Morgentaler A. Safety of testosterone therapy in men with prostate cancer. J Urol 2014;191(4):e529 –e30. DOI: 10.1016/j.juro.2014.02.1482"10.1016/j.juro.2014.02.1482Kacker R., Hult M., Conners W., Morgentaler A. Safety of testosterone therapy in men with prostate cancer. J Urol 2014;191(4):e529 –e30. DOI: 10.1016/j.juro.2014.02.1482"10.1016/j.juro.2014.02.1482Sarosdy M.F. Testosterone replacement for hypogonadism after treatment of early prostate cancer with brachytherapy. Cancer 2007;109(3):536–41. DOI: 10.1002/cncr.22438Sarosdy M.F. Testosterone replacement for hypogonadism after treatment of early prostate cancer with brachytherapy. Cancer 2007;109(3):536–41. DOI: 10.1002/cncr.22438Balbontin F.G., Moreno S.A., Bley E. et al. Long-acting testosterone injections for treatment of testosterone deficiency after brachytherapy for prostate cancer. BJU Int 2014;114(1):125–30. DOI: 10.1111/bju.12668Balbontin F.G., Moreno S.A., Bley E. et al. Long-acting testosterone injections for treatment of testosterone deficiency after brachytherapy for prostate cancer. BJU Int 2014;114(1):125–30. DOI: 10.1111/bju.12668Kadomoto S., Shigehara K., Iwamoto H. et al. Testosterone replacement therapy for patients with hypogonadism after high dose-rate brachytherapy for high-risk prostate cancer: a report of six cases and literature review. World J Mens Health 2020;38(1):132–6. DOI: 10.5534/wjmh.180130Kadomoto S., Shigehara K., Iwamoto H. et al. Testosterone replacement therapy for patients with hypogonadism after high dose-rate brachytherapy for high-risk prostate cancer: a report of six cases and literature review. World J Mens Health 2020;38(1):132–6. DOI: 10.5534/wjmh.180130Morales A., Black A.M., Emerson L.E. Testosterone administration to men with testosterone deficiency syndrome after external beam radiotherapy for localized prostate cancer: preliminary observations. BJU Int 2009;103(1):62–4. DOI: 10.1111/j.1464-410X.2008.07882.xMorales A., Black A.M., Emerson L.E. Testosterone administration to men with testosterone deficiency syndrome after external beam radiotherapy for localized prostate cancer: preliminary observations. BJU Int 2009;103(1):62–4. DOI: 10.1111/j.1464-410X.2008.07882.xDavila H.H., Arison C.N., Hall M.K. et al. Analysis of the PSA response after testosterone supplemenatation in patients who have previously received management for their localized prostate cancer. J Urol 2008;179(4S):428. DOI: 10.1016/S0022-5347(08)61255-0Davila H.H., Arison C.N., Hall M.K. et al. Analysis of the PSA response after testosterone supplemenatation in patients who have previously received management for their localized prostate cancer. J Urol 2008;179(4S):428. DOI: 10.1016/S0022-5347(08)61255-0Ory J., Flannigan R., Lundeen C. et al. Testosterone therapy in patients with treated and untreated prostate cancer: impact on oncologic outcomes. J Urol 2016;196(4):1082–9. DOI: 10.1016/j.juro.2016.04.069Ory J., Flannigan R., Lundeen C. et al. Testosterone therapy in patients with treated and untreated prostate cancer: impact on oncologic outcomes. J Urol 2016;196(4):1082–9. DOI: 10.1016/j.juro.2016.04.069Salonia A., Gallina A., Briganti A. et al. Preoperative hypogonadism is not an independent predictor of high-risk disease in patients undergoing radical prostatectomy. Cancer 2011;117(17):3953–62. DOI: 10.1002/cncr.25985Salonia A., Gallina A., Briganti A. et al. Preoperative hypogonadism is not an independent predictor of high-risk disease in patients undergoing radical prostatectomy. Cancer 2011;117(17):3953–62. DOI: 10.1002/cncr.25985Yamamoto S., Yonese J., Kawakami S. et al. Preoperative serum testosterone level as an independent predictor of treatment failure following radical prostatectomy. Eur Urol 2007;52(3):696–701. DOI: 10.1016/j.eururo.2007.03.052Yamamoto S., Yonese J., Kawakami S. et al. Preoperative serum testosterone level as an independent predictor of treatment failure following radical prostatectomy. Eur Urol 2007;52(3):696–701. DOI: 10.1016/j.eururo.2007.03.052Lumbiganon S., Patcharatrakul S., Khongcharoensombat W., Sangkum P. Pre- and post-radical prostatectomy testosterone levels in prostate cancer patients. Int J Impot Res 2019;31(2):145–9. DOI: 10.1038/s41443-019-0116-0Lumbiganon S., Patcharatrakul S., Khongcharoensombat W., Sangkum P. Pre- and post-radical prostatectomy testosterone levels in prostate cancer patients. Int J Impot Res 2019;31(2):145–9. DOI: 10.1038/s41443-019-0116-0Пушкарь Д.Ю., Роживанов Р.В., Мкртумян А.М. и др. Тестостеронзаместительная терапия в урологической практике. Междисциплинарный подход. Методические рекомендации № 59. Москва, 2019.Pushkar D.Yu., Rozhivanov R.V., Mkrtumyan A.M. et al. Testosterone replacement therapy in urological practice. Interdisciplinary approach. Methodological recommendations No. 59. Moscow, 2019. (In Russ.).Hoffman M.A., DeWolf W.C., Morgentaler A. Is low serum free testosterone a marker for high grade prostate cancer? J Urol 2000;163(3):824–7. DOI: 10.1016/S0022-5347(05)67812-3Hoffman M.A., DeWolf W.C., Morgentaler A. Is low serum free testosterone a marker for high grade prostate cancer? J Urol 2000;163(3):824–7. DOI: 10.1016/S0022-5347(05)67812-3Ribeiro M., Ruff P., Falkson G. Low serum testosterone and a younger age predict for a poor outcome in metastatic prostate cancer. Am J Clin Oncol 1997;20(6):605–8. DOI: 10.1097/00000421-199712000-00015Ribeiro M., Ruff P., Falkson G. Low serum testosterone and a younger age predict for a poor outcome in metastatic prostate cancer. Am J Clin Oncol 1997;20(6):605–8. DOI: 10.1097/00000421-199712000-00015Sofikerim M., Eskicorapci S., Oruç O., Ozen H. Hormonal predictors of prostate cancer. Urol Int 2007;79(1):13–8. DOI: 10.1159/000102906Sofikerim M., Eskicorapci S., Oruç O., Ozen H. Hormonal predictors of prostate cancer. Urol Int 2007;79(1):13–8. DOI: 10.1159/000102906Teloken C., Da Ros C.T., Caraver F. et al. Low serum testosterone levels are associated with positive surgical margins in radical retropubic prostatectomy: hypogonadism represents bad prognosis in prostate cancer. J Urol 2005;174(6):2178–80. DOI: 10.1097/01.ju.0000181818.51977.29Teloken C., Da Ros C.T., Caraver F. et al. Low serum testosterone levels are associated with positive surgical margins in radical retropubic prostatectomy: hypogonadism represents bad prognosis in prostate cancer. J Urol 2005;174(6):2178–80. DOI: 10.1097/01.ju.0000181818.51977.29Chuu C.P., Hiipakka R.A., Fukuchi J. et al. Androgen causes growth suppression and reversion of androgen-independent prostate cancer xenografts to an androgen-stimulated phenotype in athymic mice. Cancer Res 2005;65(6):2082–4. DOI: 10.1158/0008-5472.CAN-04-3992Chuu C.P., Hiipakka R.A., Fukuchi J. et al. Androgen causes growth suppression and reversion of androgen-independent prostate cancer xenografts to an androgen-stimulated phenotype in athymic mice. Cancer Res 2005;65(6):2082–4. DOI: 10.1158/0008-5472.CAN-04-3992Chen C.D., Welsbie D.S., Tran C. et al. Molecular determinants of resistance to antiandrogen therapy. Nat Med 2004;10(1):33–9. DOI: 10.1038/nm972Chen C.D., Welsbie D.S., Tran C. et al. Molecular determinants of resistance to antiandrogen therapy. Nat Med 2004;10(1):33–9. DOI: 10.1038/nm972Isaacs J.T., D’Antonio J.M., Chen S. et al. Adaptive auto-regulation of androgen receptor provides a paradigm shifting rationale for bipolar androgen therapy (BAT) for castrate resistant human prostate cancer. Prostate 2012;72(14):1491–1505. DOI: 10.1002/pros.22504Isaacs J.T., D’Antonio J.M., Chen S. et al. Adaptive auto-regulation of androgen receptor provides a paradigm shifting rationale for bipolar androgen therapy (BAT) for castrate resistant human prostate cancer. Prostate 2012;72(14):1491–1505. DOI: 10.1002/pros.22504Schweizer M.T., Antonarakis E.S., Wang H. et al. Effect of bipolar androgen therapy for asymptomatic men with castrationresistant prostate cancer: results from a pilot clinical study. Sci Transl Med 2015;7(269):269ra2. DOI: 10.1126/scitranslmed.3010563Schweizer M.T., Antonarakis E.S., Wang H. et al. Effect of bipolar androgen therapy for asymptomatic men with castrationresistant prostate cancer: results from a pilot clinical study. Sci Transl Med 2015;7(269):269ra2. DOI: 10.1126/scitranslmed.3010563Schweizer M.T., Wang H., Luber B. et al. Bipolar androgen therapy for men with androgen ablation naïve prostate cancer: results from the phase II BATMAN Study. Prostate 2016;76(13):1218–26. DOI: 10.1002/pros.23209Schweizer M.T., Wang H., Luber B. et al. Bipolar androgen therapy for men with androgen ablation naïve prostate cancer: results from the phase II BATMAN Study. Prostate 2016;76(13):1218–26. DOI: 10.1002/pros.23209Morgentaler A., Caliber M. Safety of testosterone therapy in men with prostate cancer. Expert Opin Drug Saf 2019;18(11):1065–76. DOI: 10.1080/14740338.2019.1666103Morgentaler A., Caliber M. Safety of testosterone therapy in men with prostate cancer. Expert Opin Drug Saf 2019;18(11):1065–76. DOI: 10.1080/14740338.2019.1666103

The authors declare that there are no conflicts of interest present.