urovestВестник урологииUrology Herald2308-6424Rostov State Medical University10.21886/2308-6424-2022-10-4-141-154urovest-620Research ArticleОБЗОРЫ ЛИТЕРАТУРЫREVIEWS ARTICLEАндрогенная депривационная терапия и особенности гормонального статуса у мужчин с COVID-19Androgen deprivation therapy and hormonal status in men with COVID-19https://orcid.org/0000-0003-4251-7545КамаловА. А.KamalovA. A.

Камалов Армаис Альбертович — доктор медицинских наук, профессор, академик РАН, директор Медицинского научно-образовательного центра, заведующий кафедрой урологии и андрологии факультета фундаментальной медицины МГУ им. М.В. Ломоносова.

119991, Москва, Ленинские горы, д. 1

Armais A. Kamalov — M.D., Dr.Sc.(Med), Full Prof., Academician of the Russian Academy of Sciences, Head, Dept. of Urology and Andrology, Faculty of Fundamental Medicine, Lomonosov Moscow State University; Headmaster, Medical Research and Educational Centre, Lomonosov Moscow State University.

1 Leninskie Hls., Moscow, 119991

priemnaya@mc.msu.ruhttps://orcid.org/0000-0002-6768-9004ОхоботовД. А.OhobotovD. A.

Охоботов Дмитрий Александрович — кандидат медицинских наук, доцент кафедры урологии и андрологии факультета фундаментальной медицины, врач-уролог Медицинского научно-образовательного центра МГУ им. М.В. Ломоносова.

119991, Москва, Ленинские горы, д. 1

Dmitry A. Ohobotov — M.D. Cand.Sc.(Med), Assoc.Prof. (Docent), Dept. of Urology and Andrology, Faculty of Fundamental Medicine, Lomonosov Moscow State University; Urologist, Medical Research and Education Center, Lomonosov Moscow State University.

1 Leninskie Hls., Moscow, 119991

14072003@rambler.ruhttps://orcid.org/0000-0003-3355-4547НестероваО. Ю.NesterovaO. Yu.

Нестерова Ольга Юрьевна — ординатор кафедры урологии и андрологии факультета фундаментальной медицины МГУ им. М.В. Ломоносова.

119991, Москва, Ленинские горы, д. 1

Olga Yu. Nesterova — Resident, Dept. of Urology and Andrology, Faculty of Fundamental Medicine, Lomonosov Moscow State University.

1 Leninskie Hls., Moscow, 119991

oy.nesterova@gmail.comhttps://orcid.org/0000-0003-4518-634XСтригуновА. A.StrigunovA. A.

Стригунов Андрей Алексеевич — аспирант кафедры урологии и андрологии факультета фундаментальной медицины МГУ им. М.В. Ломоносова.

119991, Москва, Ленинские горы, д. 1

Andrey A. Strigunov — M.D., Postgrad. student, Dept. of Urology and Andrology, Faculty of Fundamental Medicine, Lomonosov Moscow State University.

1 Leninskie Hls., Moscow, 119991

an-strigunov@yandex.ruhttps://orcid.org/0000-0003-0686-7935ТивтикянА. С.TivtikyanA. S.

Тивтикян Александр Сергеевич — врач-уролог Медицинского научно-образовательного центра МГУ им. М.В. Ломоносова.

119991, Москва, Ленинские горы, д. 1

Alexander S. Tivtikyan — M.D., Urologist, Medical Research and Education Center, Lomonosov Moscow State University.

1 Leninskie Hls., Moscow, 119991

aleksandertivtikyan@yandex.ruМосковский государственный университет имени М.В. ЛомоносоваРоссияLomonosov Moscow State University (Lomonosov University)Russian Federation202226122022104141154Copyright © Камалов А.А., Охоботов Д.А., Нестерова О.Ю., Стригунов А.A., Тивтикян А.С., 20232023Камалов А.А., Охоботов Д.А., Нестерова О.Ю., Стригунов А.A., Тивтикян А.С.Kamalov A.A., Ohobotov D.A., Nesterova O.Y., Strigunov A.A., Tivtikyan A.S.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.urovest.ru/jour/article/view/620

Более тяжёлое течение новой коронавирусной инфекции у мужчин по сравнению с женской половиной населения привели к детальному изучению гормонального статуса мужчин с COVID-19. Наиболее ранние работы, посвящённые данному вопросу, были сосредоточены на изучении заболеваемости и тяжести течения COVID-19 в зависимости от приёма андрогенной депривационной терапии. При этом разные классы андрогенной депривационной терапии по-разному влияют на концентрацию андрогенов, что не всегда учитывалось при анализе. В связи с этим нами был проведён обзор имеющихся литературных данных с прицельным изучением работ, включавших андрогенную депривационную терапию, однонаправленно влияющую на концентрацию мужских половых гормонов. Дополнительно были проанализированы работы, сосредоточенные на взаимосвязи COVID-19 и андрогенов (тестостерона и дигидротестостерона).

Severe course of COVID-19 among men compared to the female led to a detailed study of the hormonal status of men with COVID-19. The earliest works about this focused on the incidence and severity of COVID-19 depending on the intake of androgen deprivation therapy. At the same time, different classes of androgen deprivation therapy have different effects on androgen concentration that was not always considered in the analysis. In this regard, we conducted a review of the available literature data with a targeted study of works that included androgen deprivation therapy with a unidirectional effect on the concentration of male sex hormones. In addition, we conducted a review of studies focused on the relationship between COVID-19 and androgens (testosterone and dihydrotestosterone).

COVID-19SARS-CoV-2тестостерондигидротестостеронaнтиандрогенный эффектCOVID-19SARS-CoV-2testosteronedihydrotestosteroneantiandrogen effectReferencesHamdi S, Bendayan M, Huyghe E, Soufir JC, Amar E, El Osta R, Plotton I, Delalande C, Perrin J, Leroy C, Bouker A, Pons H, Lejeune H, Robin G, Boitrelle F. COVID-19 and andrology: Recommendations of the French-speaking society of andrology (Société d'Andrologie de langue Française SALF). Basic Clin Androl. 2020;30:10. https://doi.org/10.1186/s12610-020-00106-4Hamdi S, Bendayan M, Huyghe E, Soufir JC, Amar E, El Osta R, Plotton I, Delalande C, Perrin J, Leroy C, Bouker A, Pons H, Lejeune H, Robin G, Boitrelle F. COVID-19 and andrology: Recommendations of the French-speaking society of andrology (Société d'Andrologie de langue Française SALF). Basic Clin Androl. 2020;30:10. https://doi.org/10.1186/s12610-020-00106-4Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, Schiergens TS, Herrler G, Wu NH, Nitsche A, Müller MA, Drosten C, Pöhlmann S. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell. 2020;181(2):271-280.e8. https://doi.org/10.1016/j.cell.2020.02.052Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, Schiergens TS, Herrler G, Wu NH, Nitsche A, Müller MA, Drosten C, Pöhlmann S. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell. 2020;181(2):271-280.e8. https://doi.org/10.1016/j.cell.2020.02.052Lucas JM, Heinlein C, Kim T, Hernandez SA, Malik MS, True LD, Morrissey C, Corey E, Montgomery B, Mostaghel E, Clegg N, Coleman I, Brown CM, Schneider EL, Craik C, Simon JA, Bedalov A, Nelson PS. The androgen-regulated protease TMPRSS2 activates a proteolytic cascade involving components of the tumor microenvironment and promotes prostate cancer metastasis. Cancer Discov. 2014;4(11):1310-25. https://doi.org/10.1158/2159-8290.CD-13-1010Lucas JM, Heinlein C, Kim T, Hernandez SA, Malik MS, True LD, Morrissey C, Corey E, Montgomery B, Mostaghel E, Clegg N, Coleman I, Brown CM, Schneider EL, Craik C, Simon JA, Bedalov A, Nelson PS. The androgen-regulated protease TMPRSS2 activates a proteolytic cascade involving components of the tumor microenvironment and promotes prostate cancer metastasis. Cancer Discov. 2014;4(11):1310-25. https://doi.org/10.1158/2159-8290.CD-13-1010Роживанов Р.В., Андреева Е.Н., Мельниченко Г.А., Мокрышева Н.Г. Влияние андрогенного статуса и антиандрогенной терапии на течение COVID-19 у мужчин. Проблемы Эндокринологии. 2020;66(4):77-81. https://doi.org/10.14341/probl12500Rozhivanov R.V., Andreeva E.N., Melnichenko G.A., Mokrysheva N.G. Androgens and Antiandrogens influence on COVID-19 disease in men. Problems of Endocrinology. 2020;66(4):77-81. (In Russ.) https://doi.org/10.14341/probl12500Lieberman R. Androgen deprivation therapy for prostate cancer chemoprevention: current status and future directions for agent development. Urology. 2001;58(2 Suppl 1):83-90. https://doi.org/10.1016/s0090-4295(01)01247-xLieberman R. Androgen deprivation therapy for prostate cancer chemoprevention: current status and future directions for agent development. Urology. 2001;58(2 Suppl 1):83-90. https://doi.org/10.1016/s0090-4295(01)01247-xMontopoli M, Zumerle S, Vettor R, Rugge M, Zorzi M, Catapano CV, Carbone GM, Cavalli A, Pagano F, Ragazzi E, Prayer-Galetti T, Alimonti A. Androgen-deprivation therapies for prostate cancer and risk of infection by SARS-CoV-2: a population-based study (N = 4532). Ann Oncol. 2020;31(8):1040-1045. https://doi.org/10.1016/j.annonc.2020.04.479Montopoli M, Zumerle S, Vettor R, Rugge M, Zorzi M, Catapano CV, Carbone GM, Cavalli A, Pagano F, Ragazzi E, Prayer-Galetti T, Alimonti A. Androgen-deprivation therapies for prostate cancer and risk of infection by SARS-CoV-2: a population-based study (N = 4532). Ann Oncol. 2020;31(8):1040-1045. https://doi.org/10.1016/j.annonc.2020.04.479Gheiler EL, Tiguert R. Current concepts in androgen deprivation therapy--is there a "best" endocrine treatment? World J Urol. 2000;18(3):190-3. https://doi.org/10.1007/s003459900099Gheiler EL, Tiguert R. Current concepts in androgen deprivation therapy--is there a "best" endocrine treatment? World J Urol. 2000;18(3):190-3. https://doi.org/10.1007/s003459900099Мишугин С.В., Гринкевич А.А., Русаков И.Г. Эволюция изучения и клинического применения антиандрогенов. Медицинский совет. 2016;(10):34-7. https://doi.org/10.21518/2079-701X-2016-10-34-37Mishugin S.V., Gritskevich A.A., Rusakov I.G. Development and clinical effectiveness of antiandrogens in the treatment of advanced prostate cancer. Medical Council. 2016;(10):34-37. (In Russ.) https://doi.org/10.21518/2079-701X-2016-10-34-37Маркова А.С., Матвеев В.Б. Андрогендепривационная терапия антагонистами ЛГРГ при раке предстательной железы: лучший контроль над заболеванием при меньшем риске побочных эффектов. Результаты анализа 6 сравнительных рандомизированных исследований III фазы дегареликса и агонистой ЛГРГ. Онкоурология. 2014;(1):76-81. https://doi.org/10.17650/1726-9776-2014-10-1-76-81Markova A.S., Matveev V.B. Androgen deprivation therapy with luteinizing hormone-releasing hormone antagonists for prostate cancer: best disease control with a lower risk of side effects. results of analysis of 6 comparative randomized phase III trials of degarelix and luteinizin. Cancer Urology. 2014;10(1):76-81. (In Russ.) https://doi.org/10.17650/1726-9776-2014-10-1-76-81Бараш Ю.А., Максимов С.Я., Берштейн Л.М., Данилова М.А., Гершфельд Э.Д. Агонисты гонадотропин-рилизинг-гормона при патологии эндометрия. Журнал акушерства и женских болезней. 2008;57(4):64-72. EDN: KUGRDDBarash Y., Maximov S., Bershtein L., Gershfeld E., Danilova M. Gonadotropin-releasing hormone agonists in endometrial pathology. Journal of obstetrics and women's diseases. 2008;57(4):64-72. (In Russ.) EDN: KUGRDDWelén K, Överby AK, Ahlm C, Freyhult E, Robinsson D, Henningsson AJ, Stranne J, Bremell D, Angelin M, Lindquist E, Buckland R, Carlsson CT, Pauksens K, Bill-Axelsson A, Akre O, Ryden C, Wagenius M, Bjartell A, Nilsson AC, Styrke J, Repo J, Balkhed ÅÖ, Niward K, Gisslén M, Josefsson A. COVIDENZA - A prospective, multicenter, randomized PHASE II clinical trial of enzalutamide treatment to decrease the morbidity in patients with Corona virus disease 2019 (COVID-19): a structured summary of a study protocol for a randomised controlled trial. Trials. 2021;22(1):209. https://doi.org/10.1186/s13063-021-05137-4Welén K, Överby AK, Ahlm C, Freyhult E, Robinsson D, Henningsson AJ, Stranne J, Bremell D, Angelin M, Lindquist E, Buckland R, Carlsson CT, Pauksens K, Bill-Axelsson A, Akre O, Ryden C, Wagenius M, Bjartell A, Nilsson AC, Styrke J, Repo J, Balkhed ÅÖ, Niward K, Gisslén M, Josefsson A. COVIDENZA - A prospective, multicenter, randomized PHASE II clinical trial of enzalutamide treatment to decrease the morbidity in patients with Corona virus disease 2019 (COVID-19): a structured summary of a study protocol for a randomised controlled trial. Trials. 2021;22(1):209. https://doi.org/10.1186/s13063-021-05137-4Koskinen M, Carpen O, Honkanen V, Seppänen MRJ, Miettinen PJ, Tuominen JA, Raivio T. Androgen deprivation and SARS-CoV-2 in men with prostate cancer. Ann Oncol. 2020;31(10):1417-1418. https://doi.org/10.1016/j.annonc.2020.06.015Koskinen M, Carpen O, Honkanen V, Seppänen MRJ, Miettinen PJ, Tuominen JA, Raivio T. Androgen deprivation and SARS-CoV-2 in men with prostate cancer. Ann Oncol. 2020;31(10):1417-1418. https://doi.org/10.1016/j.annonc.2020.06.015Caffo O, Zagonel V, Baldessari C, Berruti A, Bortolus R, Buti S, Ceresoli GL, Donini M, Ermacora P, Fornarini G, Fratino L, Masini C, Massari F, Mosca A, Mucciarini C, Procopio G, Tucci M, Verri E, Zucali P, Buttigliero C. On the relationship between androgen-deprivation therapy for prostate cancer and risk of infection by SARS-CoV-2. Ann Oncol. 2020;31(10):1415-1416. https://doi.org/10.1016/j.annonc.2020.06.005Caffo O, Zagonel V, Baldessari C, Berruti A, Bortolus R, Buti S, Ceresoli GL, Donini M, Ermacora P, Fornarini G, Fratino L, Masini C, Massari F, Mosca A, Mucciarini C, Procopio G, Tucci M, Verri E, Zucali P, Buttigliero C. On the relationship between androgen-deprivation therapy for prostate cancer and risk of infection by SARS-CoV-2. Ann Oncol. 2020;31(10):1415-1416. https://doi.org/10.1016/j.annonc.2020.06.005Patel VG, Zhong X, Liaw B, Tremblay D, Tsao CK, Galsky MD, Oh WK. Does androgen deprivation therapy protect against severe complications from COVID-19? Ann Oncol. 2020;31(10):1419-1420. https://doi.org/10.1016/j.annonc.2020.06.023Patel VG, Zhong X, Liaw B, Tremblay D, Tsao CK, Galsky MD, Oh WK. Does androgen deprivation therapy protect against severe complications from COVID-19? Ann Oncol. 2020;31(10):1419-1420. https://doi.org/10.1016/j.annonc.2020.06.023Bennani NN, Bennani-Baiti IM. Androgen deprivation therapy may constitute a more effective COVID-19 prophylactic than therapeutic strategy. Ann Oncol. 2020;31(11):1585-1586. https://doi.org/10.1016/j.annonc.2020.08.2095Bennani NN, Bennani-Baiti IM. Androgen deprivation therapy may constitute a more effective COVID-19 prophylactic than therapeutic strategy. Ann Oncol. 2020;31(11):1585-1586. https://doi.org/10.1016/j.annonc.2020.08.2095Gedeborg R, Styrke J, Loeb S, Garmo H, Stattin P. Androgen deprivation therapy and excess mortality in men with prostate cancer during the initial phase of the COVID-19 pandemic. PLoS One. 2021;16(10):e0255966. https://doi.org/10.1371/journal.pone.0255966Gedeborg R, Styrke J, Loeb S, Garmo H, Stattin P. Androgen deprivation therapy and excess mortality in men with prostate cancer during the initial phase of the COVID-19 pandemic. PLoS One. 2021;16(10):e0255966. https://doi.org/10.1371/journal.pone.0255966Cadegiani FA, McCoy J, Gustavo Wambier C, Vaño-Galván S, Shapiro J, Tosti A, Zimerman RA, Goren A. Proxalutamide Significantly Accelerates Viral Clearance and Reduces Time to Clinical Remission in Patients with Mild to Moderate COVID-19: Results from a Randomized, Double-Blinded, Placebo-Controlled Trial. Cureus. 2021;13(2):e13492. https://doi.org/10.7759/cureus.13492Cadegiani FA, McCoy J, Gustavo Wambier C, Vaño-Galván S, Shapiro J, Tosti A, Zimerman RA, Goren A. Proxalutamide Significantly Accelerates Viral Clearance and Reduces Time to Clinical Remission in Patients with Mild to Moderate COVID-19: Results from a Randomized, Double-Blinded, Placebo-Controlled Trial. Cureus. 2021;13(2):e13492. https://doi.org/10.7759/cureus.13492Welén K, Rosendal E, Gisslén M, Lenman A, Freyhult E, Fonseca-Rodríguez O, Bremell D, Stranne J, Balkhed ÅÖ, Niward K, Repo J, Robinsson D, Henningsson AJ, Styrke J, Angelin M, Lindquist E, Allard A, Becker M, Rudolfsson S, Buckland R, Carlsson CT, Bjartell A, Nilsson AC, Ahlm C, Connolly AF, Överby AK, Josefsson A. A Phase 2 Trial of the Effect of Antiandrogen Therapy on COVID-19 Outcome: No Evidence of Benefit, Supported by Epidemiology and In Vitro Data. Eur Urol. 2022;81(3):285-293. https://doi.org/10.1016/j.eururo.2021.12.013Welén K, Rosendal E, Gisslén M, Lenman A, Freyhult E, Fonseca-Rodríguez O, Bremell D, Stranne J, Balkhed ÅÖ, Niward K, Repo J, Robinsson D, Henningsson AJ, Styrke J, Angelin M, Lindquist E, Allard A, Becker M, Rudolfsson S, Buckland R, Carlsson CT, Bjartell A, Nilsson AC, Ahlm C, Connolly AF, Överby AK, Josefsson A. A Phase 2 Trial of the Effect of Antiandrogen Therapy on COVID-19 Outcome: No Evidence of Benefit, Supported by Epidemiology and In Vitro Data. Eur Urol. 2022;81(3):285-293. https://doi.org/10.1016/j.eururo.2021.12.013Lee KM, Heberer K, Gao A, Becker DJ, Loeb S, Makarov DV, Gulanski B, DuVall SL, Aslan M, Lee J, Shih MC, Lynch JA, Hauger RL, Rettig M. A Population-Level Analysis of the Protective Effects of Androgen Deprivation Therapy Against COVID-19 Disease Incidence and Severity. Front Med (Lausanne). 2022;9:774773. https://doi.org/10.3389/fmed.2022.774773Lee KM, Heberer K, Gao A, Becker DJ, Loeb S, Makarov DV, Gulanski B, DuVall SL, Aslan M, Lee J, Shih MC, Lynch JA, Hauger RL, Rettig M. A Population-Level Analysis of the Protective Effects of Androgen Deprivation Therapy Against COVID-19 Disease Incidence and Severity. Front Med (Lausanne). 2022;9:774773. https://doi.org/10.3389/fmed.2022.774773Xiang Y, Wong KC, So HC. Exploring Drugs and Vaccines Associated with Altered Risks and Severity of COVID-19: A UK Biobank Cohort Study of All ATC Level-4 Drug Categories Reveals Repositioning Opportunities. Pharmaceutics. 2021;13(9):1514. https://doi.org/10.3390/pharmaceutics13091514Xiang Y, Wong KC, So HC. Exploring Drugs and Vaccines Associated with Altered Risks and Severity of COVID-19: A UK Biobank Cohort Study of All ATC Level-4 Drug Categories Reveals Repositioning Opportunities. Pharmaceutics. 2021;13(9):1514. https://doi.org/10.3390/pharmaceutics13091514McCoy J, Cadegiani FA, Wambier CG, Herrera S, Vaño-Galván S, Mesinkovska NA, Ramos PM, Shapiro J, Sinclair R, Tosti A, Goren A. 5-alpha-reductase inhibitors are associated with reduced frequency of COVID-19 symptoms in males with androgenetic alopecia. J Eur Acad Dermatol Venereol. 2021;35(4):e243-e246. Erratum in: J Eur Acad Dermatol Venereol. 2021;35(7):1595. https://doi.org/10.1111/jdv.17021McCoy J, Cadegiani FA, Wambier CG, Herrera S, Vaño-Galván S, Mesinkovska NA, Ramos PM, Shapiro J, Sinclair R, Tosti A, Goren A. 5-alpha-reductase inhibitors are associated with reduced frequency of COVID-19 symptoms in males with androgenetic alopecia. J Eur Acad Dermatol Venereol. 2021;35(4):e243-e246. Erratum in: J Eur Acad Dermatol Venereol. 2021;35(7):1595. https://doi.org/10.1111/jdv.17021Cadegiani FA, McCoy J, Gustavo Wambier C, Goren A. Early Antiandrogen Therapy With Dutasteride Reduces Viral Shedding, Inflammatory Responses, and Time-to-Remission in Males With COVID-19: A Randomized, Double-Blind, Placebo-Controlled Interventional Trial (EAT-DUTA AndroCoV Trial - Biochemical). Cureus. 2021;13(2):e13047. https://doi.org/10.7759/cureus.13047Cadegiani FA, McCoy J, Gustavo Wambier C, Goren A. Early Antiandrogen Therapy With Dutasteride Reduces Viral Shedding, Inflammatory Responses, and Time-to-Remission in Males With COVID-19: A Randomized, Double-Blind, Placebo-Controlled Interventional Trial (EAT-DUTA AndroCoV Trial - Biochemical). Cureus. 2021;13(2):e13047. https://doi.org/10.7759/cureus.13047Sari Motlagh R, Abufaraj M, Karakiewicz PI, Rajwa P, Mori K, Mun DH, Shariat SF. Association between SARS-CoV-2 infection and disease severity among prostate cancer patients on androgen deprivation therapy: a systematic review and meta-analysis. World J Urol. 2022;40(4):907-914. https://doi.org/10.1007/s00345-021-03810-6Sari Motlagh R, Abufaraj M, Karakiewicz PI, Rajwa P, Mori K, Mun DH, Shariat SF. Association between SARS-CoV-2 infection and disease severity among prostate cancer patients on androgen deprivation therapy: a systematic review and meta-analysis. World J Urol. 2022;40(4):907-914. https://doi.org/10.1007/s00345-021-03810-6Wambier CG, Vaño-Galván S, McCoy J, Gomez-Zubiaur A, Herrera S, Hermosa-Gelbard Á, Moreno-Arrones OM, Jiménez-Gómez N, González-Cantero A, Fonda-Pascual P, Segurado-Miravalles G, Shapiro J, Pérez-García B, Goren A. Androgenetic alopecia present in the majority of patients hospitalized with COVID-19: The "Gabrin sign". J Am Acad Dermatol. 2020;83(2):680-682. https://doi.org/10.1016/j.jaad.2020.05.079Wambier CG, Vaño-Galván S, McCoy J, Gomez-Zubiaur A, Herrera S, Hermosa-Gelbard Á, Moreno-Arrones OM, Jiménez-Gómez N, González-Cantero A, Fonda-Pascual P, Segurado-Miravalles G, Shapiro J, Pérez-García B, Goren A. Androgenetic alopecia present in the majority of patients hospitalized with COVID-19: The "Gabrin sign". J Am Acad Dermatol. 2020;83(2):680-682. https://doi.org/10.1016/j.jaad.2020.05.079Lee J, Yousaf A, Fang W, Kolodney MS. Male balding is a major risk factor for severe COVID-19. J Am Acad Dermatol. 2020;83(5):e353-e354. Erratum in: J Am Acad Dermatol. 2021;85(3):799. https://doi.org/10.1016/j.jaad.2020.07.062Lee J, Yousaf A, Fang W, Kolodney MS. Male balding is a major risk factor for severe COVID-19. J Am Acad Dermatol. 2020;83(5):e353-e354. Erratum in: J Am Acad Dermatol. 2021;85(3):799. https://doi.org/10.1016/j.jaad.2020.07.062Müller Ramos P, Ianhez M, Amante Miot H. Alopecia and grey hair are associated with COVID-19 Severity. Exp Dermatol. 2020;29(12):1250-1252. https://doi.org/10.1111/exd.14220Müller Ramos P, Ianhez M, Amante Miot H. Alopecia and grey hair are associated with COVID-19 Severity. Exp Dermatol. 2020;29(12):1250-1252. https://doi.org/10.1111/exd.14220Scroppo FI, Costantini E, Zucchi A, Illiano E, Trama F, Brancorsini S, Crocetto F, Gismondo MR, Dehò F, Mercuriali A, Bartoletti R, Gaeta F. COVID-19 disease in clinical setting: impact on gonadal function, transmission risk, and sperm quality in young males. J Basic Clin Physiol Pharmacol. 2021;33(1):97-102. https://doi.org/10.1515/jbcpp-2021-0227Scroppo FI, Costantini E, Zucchi A, Illiano E, Trama F, Brancorsini S, Crocetto F, Gismondo MR, Dehò F, Mercuriali A, Bartoletti R, Gaeta F. COVID-19 disease in clinical setting: impact on gonadal function, transmission risk, and sperm quality in young males. J Basic Clin Physiol Pharmacol. 2021;33(1):97-102. https://doi.org/10.1515/jbcpp-2021-0227Temiz MZ, Dincer MM, Hacibey I, Yazar RO, Celik C, Kucuk SH, Alkurt G, Doganay L, Yuruk E, Muslumanoglu AY. Investigation of SARS-CoV-2 in semen samples and the effects of COVID-19 on male sexual health by using semen analysis and serum male hormone profile: A cross-sectional, pilot study. Andrologia. 2021;53(2):e13912. https://doi.org/10.1111/and.13912Temiz MZ, Dincer MM, Hacibey I, Yazar RO, Celik C, Kucuk SH, Alkurt G, Doganay L, Yuruk E, Muslumanoglu AY. Investigation of SARS-CoV-2 in semen samples and the effects of COVID-19 on male sexual health by using semen analysis and serum male hormone profile: A cross-sectional, pilot study. Andrologia. 2021;53(2):e13912. https://doi.org/10.1111/and.13912Gul A, Zengin S, Dundar G, Ozturk M. Do SARS-CoV-2 Infection (COVID-19) and the Medications Administered for Its Treatment Impair Testicular Functions? Urol Int. 2021;105(11-12):944-948. https://doi.org/10.1159/000517925Gul A, Zengin S, Dundar G, Ozturk M. Do SARS-CoV-2 Infection (COVID-19) and the Medications Administered for Its Treatment Impair Testicular Functions? Urol Int. 2021;105(11-12):944-948. https://doi.org/10.1159/000517925Enikeev D, Taratkin M, Morozov A, Petov V, Korolev D, Shpikina A, Spivak L, Kharlamova S, Shchedrina I, Mestnikov O, Fiev D, Ganzha T, Geladze M, Mambetova A, Kogan E, Zharkov N, Demyashkin G, Shariat SF, Glybochko P. Prospective two-arm study of the testicular function in patients with COVID-19. Andrology. 2022;10(6):1047-1056. https://doi.org/10.1111/andr.13159Enikeev D, Taratkin M, Morozov A, Petov V, Korolev D, Shpikina A, Spivak L, Kharlamova S, Shchedrina I, Mestnikov O, Fiev D, Ganzha T, Geladze M, Mambetova A, Kogan E, Zharkov N, Demyashkin G, Shariat SF, Glybochko P. Prospective two-arm study of the testicular function in patients with COVID-19. Andrology. 2022;10(6):1047-1056. https://doi.org/10.1111/andr.13159Koç E, Keseroğlu BB. Does COVID-19 Worsen the Semen Parameters? Early Results of a Tertiary Healthcare Center. Urol Int. 2021;105(9-10):743-748. https://doi.org/10.1159/000517276Koç E, Keseroğlu BB. Does COVID-19 Worsen the Semen Parameters? Early Results of a Tertiary Healthcare Center. Urol Int. 2021;105(9-10):743-748. https://doi.org/10.1159/000517276Salonia A, Pontillo M, Capogrosso P, Gregori S, Carenzi C, Ferrara AM, Rowe I, Boeri L, Larcher A, Ramirez GA, Tresoldi C, Locatelli M, Cavalli G, Dagna L, Castagna A, Zangrillo A, Tresoldi M, Landoni G, Rovere-Querini P, Ciceri F, Montorsi F. Testosterone in males with COVID-19: A 7-month cohort study. Andrology. 2022;10(1):34-41. https://doi.org/10.1111/andr.13097Salonia A, Pontillo M, Capogrosso P, Gregori S, Carenzi C, Ferrara AM, Rowe I, Boeri L, Larcher A, Ramirez GA, Tresoldi C, Locatelli M, Cavalli G, Dagna L, Castagna A, Zangrillo A, Tresoldi M, Landoni G, Rovere-Querini P, Ciceri F, Montorsi F. Testosterone in males with COVID-19: A 7-month cohort study. Andrology. 2022;10(1):34-41. https://doi.org/10.1111/andr.13097Ибишев Х.С., Мамедов Э.А., Гусова З.Р., Паленный А.И., Прокоп Я.О. показатели тестостерона в сыворотке крови и гемодинамики тестикул до и после инфицирования SARS-CoV-2 (пилотное исследование). Урология. 2021;(5):5-9. https://doi.org/10.18565/urology.2021.5.5-9Ibishev KS, Mamedov EA, Gusova ZR, Palenyy AI, Prokop YO. [Serum testosterone and testicular hemodynamics before and after infection with SARS-COV-2 (pilot study)]. Urologiia. 2021;(5):5-9. (In Russ.) https://doi.org/10.18565/urology.2021.5.5-9Li C, Ye Z, Zhang AJX, Chan JFW, Song W, Liu F, Chen Y, Kwan MYW, Lee ACY, Zhao Y, Wong BHY, Yip CCY, Cai JP, Lung DC, Sridhar S, Jin D, Chu H, To KKW, Yuen KY. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection by Intranasal or Intratesticular Route Induces Testicular Damage. Clin Infect Dis. 2022;75(1):e974-e990. https://doi.org/10.1093/cid/ciac142Li C, Ye Z, Zhang AJX, Chan JFW, Song W, Liu F, Chen Y, Kwan MYW, Lee ACY, Zhao Y, Wong BHY, Yip CCY, Cai JP, Lung DC, Sridhar S, Jin D, Chu H, To KKW, Yuen KY. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection by Intranasal or Intratesticular Route Induces Testicular Damage. Clin Infect Dis. 2022;75(1):e974-e990. https://doi.org/10.1093/cid/ciac142Pagano MT, Peruzzu D, Busani L, Pierdominici M, Ruggieri A, Antinori A, D'Offizi G, Petrosillo N, Palmieri F, Piselli P, Cicalini S, Notari S, Nicastri E, Agrati C, Ippolito G, Vaia F, Gagliardi MC, Capobianchi MR, Ortona E; INMI-ISS COVID-19 team. Predicting respiratory failure in patients infected by SARS-CoV-2 by admission sex-specific biomarkers. Biol Sex Differ. 2021;12(1):63. https://doi.org/10.1186/s13293-021-00407-xPagano MT, Peruzzu D, Busani L, Pierdominici M, Ruggieri A, Antinori A, D'Offizi G, Petrosillo N, Palmieri F, Piselli P, Cicalini S, Notari S, Nicastri E, Agrati C, Ippolito G, Vaia F, Gagliardi MC, Capobianchi MR, Ortona E; INMI-ISS COVID-19 team. Predicting respiratory failure in patients infected by SARS-CoV-2 by admission sex-specific biomarkers. Biol Sex Differ. 2021;12(1):63. https://doi.org/10.1186/s13293-021-00407-xZheng S, Zou Q, Zhang D, Yu F, Bao J, Lou B, Xie G, Lin S, Wang R, Chen W, Wang Q, Teng Y, Feng B, Shen Y, Chen Y. Serum level of testosterone predicts disease severity of male COVID-19 patients and is related to T-cell immune modulation by transcriptome analysis. Clin Chim Acta. 2022;524:132-138. https://doi.org/10.1016/j.cca.2021.11.006Zheng S, Zou Q, Zhang D, Yu F, Bao J, Lou B, Xie G, Lin S, Wang R, Chen W, Wang Q, Teng Y, Feng B, Shen Y, Chen Y. Serum level of testosterone predicts disease severity of male COVID-19 patients and is related to T-cell immune modulation by transcriptome analysis. Clin Chim Acta. 2022;524:132-138. https://doi.org/10.1016/j.cca.2021.11.006Vishvakarma VK, Pal S, Singh P, Bahadur I. Interactions between main protease of SARS-CoV-2 and testosterone or progesterone using computational approach. J Mol Struct. 2022;1251:131965. https://doi.org/10.1016/j.molstruc.2021.131965Vishvakarma VK, Pal S, Singh P, Bahadur I. Interactions between main protease of SARS-CoV-2 and testosterone or progesterone using computational approach. J Mol Struct. 2022;1251:131965. https://doi.org/10.1016/j.molstruc.2021.131965Kumari K, Kumar A, Bahadur I, Singh P. Investigate the interaction of testosterone/progesterone with ionic liquids on varying the anion to combat COVID-19: Density functional theory calculations and molecular docking approach. J Phys Org Chem. 2021;34(12):e4273. https://doi.org/10.1002/poc.4273Kumari K, Kumar A, Bahadur I, Singh P. Investigate the interaction of testosterone/progesterone with ionic liquids on varying the anion to combat COVID-19: Density functional theory calculations and molecular docking approach. J Phys Org Chem. 2021;34(12):e4273. https://doi.org/10.1002/poc.4273Loschwitz J, Jäckering A, Keutmann M, Olagunju M, Eberle RJ, Coronado MA, Olubiyi OO, Strodel B. Novel inhibitors of the main protease enzyme of SARS-CoV-2 identified via molecular dynamics simulation-guided in vitro assay. Bioorg Chem. 2021;111:104862. https://doi.org/10.1016/j.bioorg.2021.104862Loschwitz J, Jäckering A, Keutmann M, Olagunju M, Eberle RJ, Coronado MA, Olubiyi OO, Strodel B. Novel inhibitors of the main protease enzyme of SARS-CoV-2 identified via molecular dynamics simulation-guided in vitro assay. Bioorg Chem. 2021;111:104862. https://doi.org/10.1016/j.bioorg.2021.104862Barbosa LP, da Silva Aguiar S, Santos PA, Dos Santos Rosa T, Maciel LA, de Deus LA, Neves RVP, de Araújo Leite PL, Gutierrez SD, Sousa CV, Korhonen MT, Degens H, Simões HG. Relationship between inflammatory biomarkers and testosterone levels in male master athletes and non-athletes. Exp Gerontol. 2021;151:111407. https://doi.org/10.1016/j.exger.2021.111407Barbosa LP, da Silva Aguiar S, Santos PA, Dos Santos Rosa T, Maciel LA, de Deus LA, Neves RVP, de Araújo Leite PL, Gutierrez SD, Sousa CV, Korhonen MT, Degens H, Simões HG. Relationship between inflammatory biomarkers and testosterone levels in male master athletes and non-athletes. Exp Gerontol. 2021;151:111407. https://doi.org/10.1016/j.exger.2021.111407Swerdloff RS, Dudley RE, Page ST, Wang C, Salameh WA. Dihydrotestosterone: Biochemistry, Physiology, and Clinical Implications of Elevated Blood Levels. Endocr Rev. 2017;38(3):220-254. https://doi.org/10.1210/er.2016-1067Swerdloff RS, Dudley RE, Page ST, Wang C, Salameh WA. Dihydrotestosterone: Biochemistry, Physiology, and Clinical Implications of Elevated Blood Levels. Endocr Rev. 2017;38(3):220-254. https://doi.org/10.1210/er.2016-1067Steward A, Bayley DL. Effects of androgens in models of rheumatoid arthritis. Agents Actions. 1992;35(3-4):268-72. https://doi.org/10.1007/BF01997510Steward A, Bayley DL. Effects of androgens in models of rheumatoid arthritis. Agents Actions. 1992;35(3-4):268-72. https://doi.org/10.1007/BF01997510Parkar M, Tabona P, Newman H, Olsen I. IL-6 expression by oral fibroblasts is regulated by androgen. Cytokine. 1998 Aug;10(8):613-9. doi: 10.1006/cyto.1998.0336.Parkar M, Tabona P, Newman H, Olsen I. IL-6 expression by oral fibroblasts is regulated by androgen. Cytokine. 1998 Aug;10(8):613-9. doi: 10.1006/cyto.1998.0336.Gornstein RA, Lapp CA, Bustos-Valdes SM, Zamorano P. Androgens modulate interleukin-6 production by gingival fibroblasts in vitro. J Periodontol. 1999;70(6):604-9. https://doi.org/10.1902/jop.1999.70.6.604Gornstein RA, Lapp CA, Bustos-Valdes SM, Zamorano P. Androgens modulate interleukin-6 production by gingival fibroblasts in vitro. J Periodontol. 1999;70(6):604-9. https://doi.org/10.1902/jop.1999.70.6.604Sánchez-García L, Wilkins-Rodriguez A, Salaiza-Suazo N, Morales-Montor J, Becker I. Dihydrotestosterone enhances growth and infectivity of Leishmania Mexicana. Parasite Immunol. 2018;40(3). https://doi.org/10.1111/pim.12512Sánchez-García L, Wilkins-Rodriguez A, Salaiza-Suazo N, Morales-Montor J, Becker I. Dihydrotestosterone enhances growth and infectivity of Leishmania Mexicana. Parasite Immunol. 2018;40(3). https://doi.org/10.1111/pim.12512Durrani F, Phelps DS, Weisz J, Silveyra P, Hu S, Mikerov AN, Floros J. Gonadal hormones and oxidative stress interaction differentially affects survival of male and female mice after lung Klebsiella pneumoniae infection. Exp Lung Res. 2012;38(4):165-72. https://doi.org/10.3109/01902148.2011.654045Durrani F, Phelps DS, Weisz J, Silveyra P, Hu S, Mikerov AN, Floros J. Gonadal hormones and oxidative stress interaction differentially affects survival of male and female mice after lung Klebsiella pneumoniae infection. Exp Lung Res. 2012;38(4):165-72. https://doi.org/10.3109/01902148.2011.654045Zhou T, Wu J, Zeng Y, Li J, Yan J, Meng W, Han H, Feng F, He J, Zhao S, Zhou P, Wu Y, Yang Y, Han R, Jin W, Li X, Yang Y, Li X. SARS-CoV-2 triggered oxidative stress and abnormal energy metabolism in gut microbiota. MedComm (2020). 2022;3(1):e112. https://doi.org/10.1002/mco2.112Zhou T, Wu J, Zeng Y, Li J, Yan J, Meng W, Han H, Feng F, He J, Zhao S, Zhou P, Wu Y, Yang Y, Han R, Jin W, Li X, Yang Y, Li X. SARS-CoV-2 triggered oxidative stress and abnormal energy metabolism in gut microbiota. MedComm (2020). 2022;3(1):e112. https://doi.org/10.1002/mco2.112Kumar N, Zuo Y, Yalavarthi S, Hunker KL, Knight JS, Kanthi Y, Obi AT, Ganesh SK. SARS-CoV-2 Spike Protein S1-Mediated Endothelial Injury and Pro-Inflammatory State Is Amplified by Dihydrotestosterone and Prevented by Mineralocorticoid Antagonism. Viruses. 2021;13(11):2209. https://doi.org/10.3390/v13112209Kumar N, Zuo Y, Yalavarthi S, Hunker KL, Knight JS, Kanthi Y, Obi AT, Ganesh SK. SARS-CoV-2 Spike Protein S1-Mediated Endothelial Injury and Pro-Inflammatory State Is Amplified by Dihydrotestosterone and Prevented by Mineralocorticoid Antagonism. Viruses. 2021;13(11):2209. https://doi.org/10.3390/v13112209Schroeder M, Tuku B, Jarczak D, Nierhaus A, Bai T, Jacobsen H, Zickler M, Mueller Z, Stanelle-Bertram S, Meinhardt A, Aberle J, Kluge S, Gabriel G. The majority of male patients with COVID-19 present low testosterone levels on admission to Intensive Care in Hamburg, Germany: a retrospective cohort study. medRxiv. 2020;05(07):20073817. https://doi.org/10.1101/2020.05.07.20073817Schroeder M, Tuku B, Jarczak D, Nierhaus A, Bai T, Jacobsen H, Zickler M, Mueller Z, Stanelle-Bertram S, Meinhardt A, Aberle J, Kluge S, Gabriel G. The majority of male patients with COVID-19 present low testosterone levels on admission to Intensive Care in Hamburg, Germany: a retrospective cohort study. medRxiv. 2020;05(07):20073817. https://doi.org/10.1101/2020.05.07.20073817Schroeder M, Schaumburg B, Mueller Z, Parplys A, Jarczak D, Roedl K, Nierhaus A, de Heer G, Grensemann J, Schneider B, Stoll F, Bai T, Jacobsen H, Zickler M, Stanelle-Bertram S, Klaetschke K, Renné T, Meinhardt A, Aberle J, Hiller J, Peine S, Kreienbrock L, Klingel K, Kluge S, Gabriel G. High estradiol and low testosterone levels are associated with critical illness in male but not in female COVID-19 patients: a retrospective cohort study. Emerg Microbes Infect. 2021;10(1):1807-1818. https://doi.org/10.1080/22221751.2021.1969869Schroeder M, Schaumburg B, Mueller Z, Parplys A, Jarczak D, Roedl K, Nierhaus A, de Heer G, Grensemann J, Schneider B, Stoll F, Bai T, Jacobsen H, Zickler M, Stanelle-Bertram S, Klaetschke K, Renné T, Meinhardt A, Aberle J, Hiller J, Peine S, Kreienbrock L, Klingel K, Kluge S, Gabriel G. High estradiol and low testosterone levels are associated with critical illness in male but not in female COVID-19 patients: a retrospective cohort study. Emerg Microbes Infect. 2021;10(1):1807-1818. https://doi.org/10.1080/22221751.2021.1969869

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