Recent molecular biology findings have shown that for the penetration of the SARS-CoV-2 coronavirus into host cells, a key role is played by protease serine 2, the activity of which is dependent on androgens. The important role of androgens is also evidenced by clinical observations that men in some age categories are infected by this novel coronavirus up to two times more frequently than women. In addition, men with androgenic alopecia tend to have more serious clinical courses, while men with androgen deprivation as a result of prostate cancer treatments tend to have milder courses. This is in line with the fact that preadolescent children are only rarely sickened with serious forms of SARS-CoV-2 infections. Even though these observations may be explained by other factors, many authors have hypothesized that lowered androgen levels and blocking their activity using anti-androgen medication may moderate the course of the viral infection in intermediately- to critically-affected cases. Clearly, it would be important for androgen deprivation to block not just gonadal androgens, but also adrenal androgens. On the other hand, low androgen levels are considered to be a risk factor for the course of SARS-CoV-2 infections, either because low androgen levels have a general effect on anabolic-catabolic equilibrium and energy metabolism, or because of the ability of testosterone to modify the immune system. It is not yet clear if infection with this novel coronavirus might induce hypogonadism, leading to undesirable side effects on male fertility.

Institute of Endocrinology Praha 1 Czech Republic

Zobrazit více v PubMed

AL-LAMI RA, URBAN RJ, VOLPI E, ALGBURI AMA, BAILLARGEON J. Sex hormones and novel corona virus infectious disease (COVID-19) Mayo Clin Proc. 2020;95:1710–1714. doi: 10.1016/j.mayocp.2020.05.013. PubMed DOI PMC

CADEGIANI FA, GOREN A, WAMBIER CG. Spironolactone may provide protection from SARS-CoV-2: Targeting androgens, angiotensin converting enzyme 2 (ACE2), and renin-angiotensin-aldosterone system (RAAS) Med Hypotheses. 2020;143:110112. doi: 10.1016/j.mehy.2020.110112. PubMed DOI PMC

CADEGIANI FA, LIM RK, GOREN A, McCOY J, SITUM M, KOVACEVIC M, VAÑÓ GALVÁN S, SINCLAIR R, TOSTI A, WAMBIER CG. Clinical symptoms of hyperandrogenic women diagnosed with COVID-19. J Eur Acad Dermatol Venereol. 2021;15:e101–e104. doi: 10.1111/jdv.17004. PubMed DOI

CATTRINI C, BERSANELLI M, LATOCCA MM, CONTE B, VALLOME G, BOCCARDO F. Sex hormones and hormone therapy during COVID-19 pandemic: Implications for patients with cancer. Cancers (Basel) 2020;12:2325. doi: 10.3390/cancers12082325. PubMed DOI PMC

DUTTA S, SENGUPTA P. SARS-CoV-2 and male infertility: Possible multifaceted pathology. Reprod Sci. 2021;28:23–26. doi: 10.1007/s43032-020-00261-z. PubMed DOI PMC

GIAGULLI VA, GUASTAMACCHIA E, MAGRONE T, JIRILLO E, LISCO G, De PERGOLA G, TRIGGIANI V. Worse progression of COVID-19 in men: Is testosterone a key factor? Andrology. 2021;9:53–64. doi: 10.1111/andr.12836. PubMed DOI PMC

GOREN A, McCOY J, WAMBIER CG, VANO-GALVAN S, SHAPIRO J, DHURAT R, WASHENIK K, LOTTI T. What does androgenetic alopecia have to do with COVID-19? An insight into a potential new therapy. Dermatol Ther. 2020a;33:e13365. doi: 10.1111/dth.13365. PubMed DOI PMC

GOREN A, VAÑO-GALVÁN S, WAMBIER CG, McCOY J, GOMEZ-ZUBIAUR A, MORENO-ARRONES OM, SHAPIRO J, SINCLAIR RD, GOLD MH, KOVACEVIC M, MESINKOVSKA NA, GOLDUST M, WASHENIK K. A preliminary observation: Male pattern hair loss among hospitalized COVID-19 patients in Spain - A potential clue to the role of androgens in COVID-19 severity. J Cosmet Dermatol. 2020b;19:1545–1547. doi: 10.1111/jocd.13443. PubMed DOI

GOREN A, WAMBIER CG, HERRERA S, McCOY J, VAÑO-GALVÁN S, GIOIA F, COMECHE B, RON R, SERRANO-VILLAR S, RAMOS PM, CADEGIANI FA, KOVACEVIC M, TOSTI A, SHAPIRO J, SINCLAIR RJ. Anti-androgens may protect against severe COVID-19 outcomes: results from a prospective cohort study of 77 hospitalized men. J Eur Acad Dermatol Venereol. 2021c;35:e13–e15. doi: 10.1111/jdv.16953. PubMed DOI PMC

GRUBIC KEZELE T. Androgen-driven COVID-19 infection - is testosterone an enemy or a friend? Hormone Mol Biol Clin Invest. 2020;41:20200027. doi: 10.1515/hmbci-2020-0027. PubMed DOI

GURWITZ D. Angiotensin receptor blockers as tentative SARS-CoV-2 therapeutics. Drug Dev Res. 2020;81:537–540. doi: 10.1002/ddr.21656. PubMed DOI PMC

HAGHPANAH A, MASJEDI F, ALBORZI S, HOSSEINPOUR A, DEHGHANI A, MALEKMAKAN L, ROOZBEH J. Potential mechanisms of SARS.CoV-2 action on male gonadal function and fertility. Current status and future prospects. Andrologia. 2021;53:e13883. doi: 10.1111/and.13883. PubMed DOI PMC

HOFFMANN M, KLEINE-WEBER H, SCHROEDER S. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell. 2020;181:271–280. doi: 10.1016/j.cell.2020.02.052. PubMed DOI PMC

HUSSAIN AN, HUSSAIN F, HAS HMI SK. Role of testosterone in COVID-19 patients - A double-edged sword? Med Hypotheses. 2020;144:110287. doi: 10.1016/j.mehy.2020.110287. PubMed DOI PMC

JONES AL, JAEGER B, SCHILD C. No credible evidence for links between 2D:4D and covid outcomes: A probabilistic perspective on digit ratio, ACE variants, and national case fatalities. Early Hum Dev. 2021;152:105272. doi: 10.1016/j.earlhumdev.2020.105272. PubMed DOI PMC

KADIHASANOGLU M, AKTAS S, YARDIMCI E, ARAL H, KADIOGLU A. SARS-CoV-2 pneumonia affects male reproductive hormone levels: A prospective, cohort study. J Sex Med. 2021;18:256–264. doi: 10.1016/j.jsxm.2020.11.007. PubMed DOI PMC

KARLBERG J, CHONG DSY, LAI WYY. Do men have a higher case fatality rate of severe acute respiratory syndrome than women do? Am J Epidemiol. 2004;159:229–231. doi: 10.1093/aje/kwh056. PubMed DOI PMC

KLEIN EA, LI J, MILINOVICH A, SCHOLD JD, SHARIFI N, KATTAN MW, JEHI L. Androgen deprivation therapy in men with prostate cancer does not affect risk of infection with SARS-CoV-2. J Urol. 2021;205:441–443. doi: 10.1097/JU.0000000000001338. PubMed DOI

LA VIGNERA S, CANNARELLA R, CONDORELLI RA. Sex-specific SARS-CoV-2 mortality: among hormone-modulated ACE2 expression, risk of venous thromboembolism and hypovitaminosis D. Int J Mol Sci. 2020;21:2948. doi: 10.3390/ijms21082948. PubMed DOI PMC

LUCAS JM, HEINLEIN C, KIM T. The androgen-regulated protease TMPRSS2 activates a proteolytic cascade involving components of the tumor microenvironment and promotes prostate cancer metastasis. Cancer Discov. 2014;4:1310–1325. doi: 10.1158/2159-8290.CD-13-1010. PubMed DOI PMC

MANNING JT, FINK B. Understanding COVID-19: digit ratio (2D:4D) and sex differences in national case fatality rates. Early Hum Dev. 2020;146:105074. doi: 10.1016/j.earlhumdev.2020.105074. PubMed DOI PMC

McCOY J, WAMBIER CG, VANO-GALVAN S, SHAPIRO J, SINCLAIR R, RAMOS PM, WASHENIK K, ANDRADE M, HERRERA S, GOREN A. Racial variations in COVID-19 deaths may be due to androgen receptor genetic variants associated with prostate cancer and androgenetic alopecia. Are anti-androgens a potential treatment for COVID-19? J Cosmet Dermatol. 2020;19:1542–1543. doi: 10.1111/jocd.13455. PubMed DOI PMC

MONTOPOLI 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;31:1040–1045. doi: 10.1016/j.annonc.2020.04.479. PubMed DOI PMC

MORGANTE G, TROIA L, De LEO V. Coronavirus disease 2019 (SARS-CoV-2) and polycystic ovarian disease: Is there a higher risk for these women? J Steroid Biochem Mol Biol. 2021;205:105770. doi: 10.1016/j.jsbmb.2020.105770. PubMed DOI PMC

OKÇELIK S. COVID-19 pneumonia causes lower testosterone levels. Andrologia. 2021;53:e13909. doi: 10.1111/and.13909. PubMed DOI PMC

PACES J, STRIZOVA Z, SMRZ D, CERNY J. COVID-19 and the immune system. Physiol Res. 2020;69:379–388. doi: 10.33549/physiolres.934492. PubMed DOI PMC

PAPADOPOULOS V, LI L, SAMPLASKI M. Why does COVID-19 kill more elderly men than women? Is there a role for testosterone? Andrology. 2021;9:65–72. doi: 10.1111/andr.12868. PubMed DOI PMC

POZZILLI P, LENZI A. Commentary: Testosterone, a key hormone in the context of COVID-19 pandemic. Metabolism. 2020;108:154252. doi: 10.1016/j.metabol.2020.154252. PubMed DOI PMC

RAMBHATLA A, BRONKEMA CJ, CORSI N, KEELEY J, SOOD A, AFFAS Z, DABAJA AA, ROGERS CG, LIROFF SA, ABDOLLAH F. COVID-19 Infection in men on testosterone replacement therapy. J Sex Med. 2021;18:215–218. doi: 10.1016/j.jsxm.2020.09.013. PubMed DOI PMC

RASTRELLI G, Di STASI V, INGLESE F, BECCARIA M, GARUTI M, Di COSTANZO D, SPREAFICO F, GRECO GF, CERVI G, PECORIELLO A, MAGINI A, TODISCO T, CIPRIANI S, MASEROLI E, CORONA G, SALONIA A, LENZI A, MAGGI M, De DONNO G, VIGNOZZI L. Low testosterone levels predict clinical adverse outcomes in SARS-CoV-2 pneumonia patients. Andrology. 2021;9:88–98. doi: 10.1111/andr.12821. PubMed DOI PMC

ROWLAND SP, O’BRIEN BERGIN E. Screening for low testosterone is needed for early identification and treatment of men at high risk of mortality from Covid-19. Crit Care. 2020;24:367. doi: 10.1186/s13054-020-03086-z. PubMed DOI PMC

RUAN Y, HU B, LIU Z, LIU K, JIANG H, LI H, LI R, LUAN Y, LIU X, YU G, XU S, YUAN X, WANG S, YANG W, YE Z, LIU J, WANG T. No detection of SARS-CoV-2 from urine, expressed prostatic secretion, and semen in 74 recovered COVID-19 male patients: A perspective and urogenital evaluation. Andrology. 2021;9:99–106. doi: 10.1111/andr.12939. PubMed DOI

SANSONE A, MOLLAIOLI D, CIOCCA G, LIMONCIN E, COLONNELLO E, VENA W, JANNINI EA. Addressing male sexual and reproductive health in the wake of COVID-19 outbreak. J Endocrinol Invest. 2021;44:223–231. doi: 10.1007/s40618-020-01350-1. PubMed DOI PMC

SHI Y, WANG Y, SHAO C. COVID-19 infection: the perspectives on immune responses. Cell Death Differ. 2020;27:1451–1454. doi: 10.1038/s41418-020-0530-3. PubMed DOI PMC

ŠIMKOVÁ M, VÍTKŮ J, KOLÁTOROVÁ L, VRBÍKOVÁ J, VOSÁTKOVÁ M, VČELÁK J, DUŠKOVÁ M. Endocrine disruptors, obesity, and cytokines - How relevant are they to PCOS? Physiol Res. 2020;69(Suppl 2):S279–S293. doi: 10.33549/physiolres.934521. PubMed DOI PMC

STÁRKA L, DUŠKOVÁ M, POSPÍŠILOVÁ H, HILL M. Estradiol, obesity and hypogonadism. Physiol Res. 2020a;69(Suppl 2):S273–S278. doi: 10.33549/physiolres.934510. PubMed DOI PMC

STÁRKA L, VÍTKŮ J, DUŠKOVÁ M. 11-Keto-testosterone and other androgens of adrenal origin. Physiol Res. 2020b;69(Suppl 2):S187–S192. doi: 10.33549/physiolres.934516. PubMed DOI PMC

SUBRAMANIAN A, ANAND A, ADDERLEY N, OKOTH K, TOULIS KA, GOKHALE K, SAINSBURY C, O’REILLY MW, WIEBKE A, NIRANTHARAKUMAR K. Increased COVID-19 infections in women with polycystic ovary syndrome: a population-based study. Eur J Endocrinol. 2021;184:637–645. doi: 10.1530/EJE-20-1163. PubMed DOI PMC

VAŠKŮ A. Covid-19 infection and the host genetic predisposition: does it exist? Physiol Res. 2020;69:511–514. doi: 10.33549/physiolres.934504. PubMed DOI PMC

WADMAN M. Sex hormones signals why virus hits men harder. Science. 2020;368:1038–1039. doi: 10.1126/science.368.6495.1038. PubMed DOI

WAMBIER C, GOREN A. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is likely to be androgen mediated. J Am Acad Dermatol. 2020a;83:308–309. doi: 10.1016/j.jaad.2020.04.032. PubMed DOI PMC

WAMBIER 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. 2020b;83:680–682. doi: 10.1016/j.jaad.2020.05.079. PubMed DOI PMC

WAMBIER CG, GOREN A, VAÑO-GALVÁN S, RAMOS PM, OSSIMETHA A, NAU G, HERRERA S, McCOY J. Androgen sensitivity gateway to COVID-19 disease severity. Drug Dev Drug Dev Res. 2020;81:771–776. doi: 10.1002/ddr.21688. PubMed DOI PMC

WENHAM C, SMITH J, MORGAN R. COVID-19: The gendered impact of the outbreak. Lancet. 2020;395:846–848. doi: 10.1016/S0140-6736(20)30526-2. PubMed DOI PMC

XU H, WANG Z, FENG C, YU W, CHEN Y, ZENG X, LIU C. Effects of SARS-CoV-2 infection on male sex-related hormones in recovering patients. Andrology. 2021;9:107–114. doi: 10.1111/andr.12942. PubMed DOI

YOUNIS JS, SKORECI K, ABASSI Z. The double edge sword of testosterone’s role in the COVID-19 pandemic. Front Endocrinol (Lausanne) 2021;12:607179. doi: 10.3389/fendo.2021.607179. PubMed DOI PMC

Antiviral activity of amiodarone in SARS-CoV-2 disease

COVID-19, oxidative stress, and male reproductive dysfunctions: is vitamin C a potential remedy?