Impact of COVID-19 on testicular function: a systematic review and meta-analysis.

COVID-19 Infertility SARS-CoV2 Testicular function Testosterone

Journal

Endocrine
ISSN: 1559-0100
Titre abrégé: Endocrine
Pays: United States
ID NLM: 9434444

Informations de publication

Date de publication:
12 Feb 2024
Historique:
received: 28 12 2023
accepted: 17 01 2024
medline: 12 2 2024
pubmed: 12 2 2024
entrez: 12 2 2024
Statut: aheadofprint

Résumé

Studies investigating the effects of SARS-CoV-2 on male reproductive function are few and heterogeneous, and results are often conflicting. This systematic review and meta-analysis was carried out on studies conducted in men with active or anamnestic SARS-CoV-2 infection to evaluate its consequences on the male sex hormone profile and semen parameters. This meta-analysis follows the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) protocols. PubMed, Scopus, Cochrane, and Embase databases were searched to identify relevant studies. We originally selected 3553 articles. After the eligibility phase, 16 articles met our inclusion criteria encompassing 11 case-control studies and 5 cohort studies (2 prospective and 3 retrospective studies). We performed the quantitative analysis with Comprehensive Meta-Analysis Software. Cochran-Q and heterogeneity (I Overall, 1250 patients with active or recent (up to 80 days before) COVID-19 infection and 1232 matched healthy controls were included. Sperm concentration, total sperm count, and total motility were significantly lower in patients compared with controls. Patients also showed lower levels of total testosterone and follicle-stimulating hormone, and higher levels of luteinizing hormone, 17β-estradiol, and prolactin compared with healthy controls. None of the included studies found the presence of SARS-CoV-2 mRNA in the semen of infected patients. The present systematic review and meta-analysis suggests the presence of an association between SARS-CoV-2 infection and primary testicular damage manifested with a picture of altered steroidogenesis and worsening spermatogenesis. The absence of the virus in the seminal fluid indicates a low possibility of sexual transmission of the infection to partners and offspring. However, our findings mostly show short-term follow-up, while few studies have considered the long-term consequences of the viral infection, thus further studies are needed to evaluate the long-term consequences on male reproductive health.

Identifiants

pubmed: 38345682
doi: 10.1007/s12020-024-03705-7
pii: 10.1007/s12020-024-03705-7
doi:

Types de publication

Journal Article Review

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© 2024. The Author(s).

Références

F. Wu, S. Zhao, B. Yu, Y.M. Chen, W. Wang, Z.G. Song et al. A new coronavirus associated with human respiratory disease in China. Nature 579(7798), 265–269 (2020)
pubmed: 32015508 pmcid: 7094943 doi: 10.1038/s41586-020-2008-3
L. Chen, Q. Li, D. Zheng, H. Jiang, Y. Wei, L. Zou et al. Correspondence: clinical characteristics of Covid-19 in Wuhan China. N. Engl. J. Med. 100, 1 (2020)
S. La Vignera, R. Cannarella, R.A. Condorelli, F. Torre, A. Aversa, A.E. Calogero, Sex-specific SARS-CoV2 mortality: among hormone-modulated ace2 expression, risk of venous thromboembolism and hypovitaminosis D. Int. J. Mol. Sci. 21(8), 5–10 (2020)
doi: 10.3390/ijms21082948
L. Marinelli, G. Beccuti, M. Zavattaro, S. Cagnina, I. Gesmundo, C. Bona et al. Testosterone as a biomarker of adverse clinical outcomes in SARS-CoV-2 pneumonia. Biomedicines 10(4), 1–11 (2022)
doi: 10.3390/biomedicines10040820
A. Alamo, C. De Luca, L.M. Mongioì, F. Barbagallo, R. Cannarella, S. La Vignera, A.E. Calogero, R.A. Condorelli, Mitochondrial Membrane Potential Predicts 4-Hour Sperm Motility. Biomedicines 8(7), 196 (2020). https://doi.org/10.3390/biomedicines8070196
K.E. Stanley, E. Thomas, M. Leaver, D. Wells, Coronavirus disease-19 and fertility: viral host entry protein expression in male and female reproductive tissues. Fertil. Steril. 114(1), 33–43 (2020). https://doi.org/10.1016/j.fertnstert.2020.05.001
doi: 10.1016/j.fertnstert.2020.05.001 pubmed: 32622411 pmcid: 7205710
A. Sansone, D. Mollaioli, G. Ciocca, E. Limoncin, E. Colonnello, W. Vena et al. Addressing male sexual and reproductive health in the wake of COVID-19 outbreak. J. Endocrinol. Invest. 44(2), 223–231 (2021). https://doi.org/10.1007/s40618-020-01350-1
doi: 10.1007/s40618-020-01350-1 pubmed: 32661947
J. Xu, L. Qi, X. Chi, J. Yang, X. Wei, E. Gong et al. Orchitis: a complication of severe acute respiratory syndrome (SARS). Biol. Reprod. 74(2), 410–416 (2006)
pubmed: 16237152 doi: 10.1095/biolreprod.105.044776
M. Bendayan, F. Boitrelle, What could cause the long-term effects of COVID-19 on sperm parameters and male fertility? QJM 114(4), 287 (2021)
pubmed: 33561263 doi: 10.1093/qjmed/hcab028
R. Channappanavar, C. Fett, M. Mack, P.P. Ten Eyck, S. Perlman, I. City et al. Sex-based differences in susceptibility to SARS-CoV infection. J. Immunol. 198(10), 319–335 (2018)
L. Lanser, F.R. Burkert, L. Thommes, A. Egger, G. Hoermann, S. Kaser et al. Testosterone deficiency is a risk factor for severe COVID-19. Front. Endocrinol. 12, 1–12 (2021)
doi: 10.3389/fendo.2021.694083
M. Zaigham, A. Holmberg, M.L. Karlberg, O.K. Lindsjö, L. Jokubkiene, J. Sandblom et al. Intrauterine vertical SARS-CoV-2 infection: a case confirming transplacental transmission followed by divergence of the viral genome. BJOG Int. J. Obstet. Gynaecol. 128(8), 1388–1394 (2021)
doi: 10.1111/1471-0528.16682
M.Y. Valdespino-Vázquez, C.A. Helguera-Repetto, M. León-Juárez, O. Villavicencio-Carrisoza, A. Flores-Pliego, E.R. Moreno-Verduzco et al. Fetal and placental infection with SARS-CoV-2 in early pregnancy. J. Med. Virol. 93(7), 4480–4487 (2021)
pubmed: 33764543 pmcid: 8250563 doi: 10.1002/jmv.26965
G. Rastrelli, V. Di Stasi, F. Inglese, M. Beccaria, M. Garuti, D. Di Costanzo et al. Low testosterone levels predict clinical adverse outcomes in SARS-CoV-2 pneumonia patients. Andrology 9(1), 88–98 (2021)
pubmed: 32436355 doi: 10.1111/andr.12821
S. Dhindsa, N. Zhang, M.J. McPhaul, Z. Wu, A.K. Ghoshal, E.C. Erlich, K. Mani, G.J. Randolph, J.R. Edwards, P.A. Mudd, A. Diwan, Association of Circulating Sex Hormones With Inflammation and Disease Severity in Patients With COVID-19. JAMA Netw Open 4(5), e2111398 (2021). https://doi.org/10.1001/jamanetworkopen.2021.11398
L. Kim, S. Garg, A. O’Halloran, M. Whitaker, H. Pham, E.J. Anderson et al. Risk factors for intensive care unit admission and in-hospital mortality among hospitalized adults identified through the US Coronavirus Disease 2019 (COVID-19)-Associated Hospitalization Surveillance Network (COVID-NET). Clin. Infect. Dis. 72(9), E206–E214 (2021)
pubmed: 32674114 doi: 10.1093/cid/ciaa1012
F. Barbagallo, A.E. Calogero, R. Cannarella, R.A. Condorelli, L.M. Mongioì, A. Aversa et al. The testis in patients with COVID-19: virus reservoir or immunization resource? Transl. Androl. Urol. 9(5), 1897–1900 (2020)
pubmed: 33209652 pmcid: 7658157 doi: 10.21037/tau-20-900
M. Iwasaki, J. Saito, H. Zhao, A. Sakamoto, K. Hirota, D. Ma, Inflammation triggered by SARS-CoV-2 and ACE2 augment drives multiple organ failure of severe COVID-19: molecular mechanisms and implications. Inflammation 44(1), 13–34 (2021)
pubmed: 33029758 doi: 10.1007/s10753-020-01337-3
S. Çayan, M. Uğuz, B. Saylam, E. Akbay, Effect of serum total testosterone and its relationship with other laboratory parameters on the prognosis of coronavirus disease 2019 (COVID-19) in SARS-CoV-2 infected male patients: a cohort study. Aging Male 23(5), 1493–1503 (2021). https://doi.org/10.1080/13685538.2020.1807930
doi: 10.1080/13685538.2020.1807930
A.E. Cinislioglu, N. Cinislioglu, S.O. Demirdogen, E. Sam, F. Akkas, M.S. Altay et al. The relationship of serum testosterone levels with the clinical course and prognosis of COVID-19 disease in male patients: a prospective study. Andrology 10(1), 24–33 (2022)
pubmed: 34288536 doi: 10.1111/andr.13081
M. Kadihasanoglu, S. Aktas, E. Yardimci, H. Aral, Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company’s public news and information. (2020)
A.S. Patel, J.Y. Leong, L. Ramos, R. Ramasamy, Testosterone is a contraceptive and should not be used in men who desire fertility. World J. Mens Health 37(1), 45–54 (2019)
pubmed: 30350483 doi: 10.5534/wjmh.180036
S. Okçelik, COVID-19 pneumonia causes lower testosterone levels. Andrologia 53(1), 1–4 (2021)
doi: 10.1111/and.13909
K. Selvaraj, S. Ravichandran, S. Krishnan, R.K. Radhakrishnan, N. Manickam, M. Kandasamy, Testicular atrophy and hypothalamic pathology in COVID-19: possibility of the incidence of male infertility and HPG axis abnormalities. Reprod. Sci. 28(10), 2735–2742 (2021)
pubmed: 33415647 doi: 10.1007/s43032-020-00441-x
H. Rosen, M.L. Jameel, A.L. Barkan, Dexamethasone suppresses gonadotropin-releasing hormone (GnRH) secretion and has direct pituitary effects in male rats: differential regulation of gnrh receptor and gonadotropin responses to GnRH. Endocrinology 122(6), 2873–2880 (1988)
pubmed: 2836177 doi: 10.1210/endo-122-6-2873
L.F. Perez-Garcia, B. te Winkel, J.P. Carrizales, W. Bramer, S. Vorstenbosch, E. van Puijenbroek et al. Sexual function and reproduction can be impaired in men with rheumatic diseases: a systematic review. Semin. Arthritis Rheum. 50(3), 557–573 (2020). https://doi.org/10.1016/j.semarthrit.2020.02.002
doi: 10.1016/j.semarthrit.2020.02.002 pubmed: 32165034
S. Bank, S.K. De, B. Bankura, S. Maiti, M. Das, G.A. Khan, Ace/ace2 balance might be instrumental to explain the certain comorbidities leading to severe covid-19 cases. Biosci. Rep. 41(2), 41–46 (2021)
doi: 10.1042/BSR20202014
C. Fan, W. Lu, K. Li, Y. Ding, J. Wang, ACE2 expression in kidney and testis may cause kidney and testis infection in COVID-19 patients. Front. Med. 7, 1–9 (2021)
doi: 10.3389/fmed.2020.563893
S. Colaco, K. Chhabria, D. Singh, A. Bhide, N. Singh, A. Singh et al. Expression map of entry receptors and infectivity factors for pan-coronaviruses in preimplantation and implantation stage human embryos. J. Assist. Reprod. Genet. 38(7), 1709–1720 (2021)
pubmed: 33913101 pmcid: 8081283 doi: 10.1007/s10815-021-02192-3
G. Mjaess, A. Karam, F. Aoun, S. Albisinni, T. Roumeguère, COVID-19 and the male susceptibility: the role of ACE2, TMPRSS2 and the androgen receptor. Prog. Urol. 30(10), 484–487 (2020). https://doi.org/10.1016/j.purol.2020.05.007
doi: 10.1016/j.purol.2020.05.007 pubmed: 32620366 pmcid: 7242948
E. Taglauer, Y. Benarroch, K. Rop, E. Barnett, V. Sabharwal, C. Yarrington et al. Consistent localization of SARS-CoV-2 spike glycoprotein and ACE2 over TMPRSS2 predominance in placental villi of 15 COVID-19 positive maternal-fetal dyads. Placenta 100, 69–74 (2020). https://doi.org/10.1016/j.placenta.2020.08.015
doi: 10.1016/j.placenta.2020.08.015 pubmed: 32862058 pmcid: 7445146
J. Qi, Y. Zhou, J. Hua, L. Zhang, J. Bian, B. Liu et al. The scRNA-seq expression profiling of the receptor ACE2 and the cellular protease TMPRSS2 reveals human organs susceptible to SARS-CoV-2 infection. Int. J. Environ. Res. Public Health 18(1), 1–17 (2021)
doi: 10.3390/ijerph18010284
L.M. Wong, G. Jiang, A plausible link of tmprss2/ace2/ar signaling to male mortality during the COVID-19 pandemic in the United States. Pathogens 10(11), 1–10 (2021)
doi: 10.3390/pathogens10111378
D. Cui, Y. Liu, X. Jiang, C. Ding, L.C. Poon, H. Wang et al. Single-cell RNA expression profiling of SARS-CoV-2-related ACE2 and TMPRSS2 in human trophectoderm and placenta. Ultrasound Obstet. Gynecol. 57(2), 248–256 (2021)
pubmed: 32851697 pmcid: 7461088 doi: 10.1002/uog.22186
N. Moghimi, B. Eslami Farsani, M. Ghadipasha, G.R. Mahmoudiasl, A. Piryaei, A. Aliaghaei et al. COVID-19 disrupts spermatogenesis through the oxidative stress pathway following induction of apoptosis. Apoptosis 26(7–8), 415–430 (2021). https://doi.org/10.1007/s10495-021-01680-2
doi: 10.1007/s10495-021-01680-2 pubmed: 34076792 pmcid: 8170653
C. Massarotti, A. Garolla, E. Maccarini, P. Scaruffi, S. Stigliani, P. Anserini et al. SARS-CoV-2 in the semen: where does it come from? Andrology 9(1), 39–41 (2021)
pubmed: 32533891 doi: 10.1111/andr.12839
S. Abdollahpour, S. Badiee Aval, T. Khadivzadeh, Do not neglect the Covid-19 transmission through sexual intercourse. J. Sex. Marital Ther. 47(7), 731–737 (2021). https://doi.org/10.1080/0092623X.2021.1938765
doi: 10.1080/0092623X.2021.1938765 pubmed: 34346289
M.J. Perry, S. Arrington, L.M. Neumann, D. Carrell, C.N. Mores, It is currently unknown whether SARS-CoV-2 is viable in semen or whether COVID-19 damages spermatozoa. Andrology 9(1), 30–32 (2021)
pubmed: 32471002 doi: 10.1111/andr.12831
A.M. Methley, S. Campbell, C. Chew-Graham, R. McNally, S. Cheraghi-Sohi, PICO, PICOS and SPIDER: a comparison study of specificity and sensitivity in three search tools for qualitative systematic reviews. BMC Health Serv. Res. 14, 1 (2014)
doi: 10.1186/s12913-014-0579-0
X. Wan, W. Wang, J. Liu, T. Tong, Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range. BMC Med. Res. Methodol. 14(1), 1–13 (2014)
doi: 10.1186/1471-2288-14-135
J. Murray, D.P. Farrington, M.P. Eisner, Drawing conclusions about causes from systematic reviews of risk factors: the Cambridge Quality Checklists. J. Exp. Criminol. 5(1), 1–23 (2009)
doi: 10.1007/s11292-008-9066-0
T.-H. Guo, M.-Y. Sang, S. Bai, H. Ma, Y.-Y. Wan, X.-H. Jiang, Y.-W. Zhang, B. Xu, H. Chen, X.-Y. Zheng, S.-H. Luo, X.-F. Xie, C.-J. Gong, J.-P. Weng, Q.-H. Shi, Semen parameters in men recovered from COVID-19. Asian J. Androl. (2021). https://pubmed.ncbi.nlm.nih.gov/33975987/#:~:text=Thetotalspermcount%2Cspermconcentration%2Candnumberofmotileinthe22patientsexamined
T. Chen, D. Wu, H. Chen, W. Yan, D. Yang, G. Chen, K. Ma, D. Xu, H. Yu, H. Wang, T. Wang, W. Guo, J. Chen, C. Ding, X. Zhang, J. Huang, M. Han, S. Li, X. Luo, J. Zhao, Q. Ning, Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study. BMJ 368, m1091 (2020). Erratum in: BMJ. 368, m1295 (2020). https://doi.org/10.1136/bmj.m1091
M.Z. Temiz, M.M. Dincer, I. Hacibey, R.O. Yazar, C. Celik, S.H. Kucuk et al. 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 53(2), 1–9 (2021)
doi: 10.1111/and.13912
J.C. Best, M. Kuchakulla, K. Khodamoradi, T.F.N. Lima, F.S. Frech, J. Achua et al. Evaluation of SARS-CoV-2 in human semen and effect on total sperm number: a prospective observational study. World J. Mens Health 39(3), 489–495 (2021)
pubmed: 33663031 pmcid: 8255403 doi: 10.5534/wjmh.200192
Y. Ruan, B. Hu, Z. Liu, K. Liu, H. Jiang, H. Li et al. No detection of SARS-CoV-2 from urine, expressed prostatic secretions, and semen in 74 recovered COVID-19 male patients: a perspective and urogenital evaluation. Andrology 9(1), 99–106 (2021)
pubmed: 33150723 doi: 10.1111/andr.12939
H. Li, X. Xiao, J. Zhang, M.I. Zafar, C. Wu, Y. Long et al. Impaired spermatogenesis in COVID-19 patients. EClinicalMedicine 28, 100604 (2020). https://doi.org/10.1016/j.eclinm.2020.100604
doi: 10.1016/j.eclinm.2020.100604 pubmed: 33134901 pmcid: 7584442
N. Holtmann, P. Edimiris, M. Andree, C. Doehmen, D. Baston-Buest, O. Adams et al. Assessment of SARS-CoV-2 in human semen—a cohort study. Fertil. Steril. 114(2), 233–238 (2020)
pubmed: 32650948 pmcid: 7256599 doi: 10.1016/j.fertnstert.2020.05.028
H. Piroozmanesh, E. Cheraghi, L. Naserpoor, M. Aghashahi, R. Jannatifar, The effect of COVID-19 infection on sperm quality and male fertility. Jentashapir J. Cell Mol. Biol. 12(2), e115390 (2021). https://doi.org/10.5812/jjcmb.115390
doi: 10.5812/jjcmb.115390
H. Xu, Z. Wang, C. Feng, W. Yu, Y. Chen, X. Zeng et al. Effects of SARS-CoV-2 infection on male sex-related hormones in recovering patients. Andrology 9(1), 107–114 (2021)
pubmed: 33152165 doi: 10.1111/andr.12942
L. Ma, W. Xie, D. Li, L. Shi, G. Ye, Y. Mao et al. Evaluation of sex-related hormones and semen characteristics in reproductive-aged male COVID-19 patients. J. Med. Virol. 93(1), 456–462 (2021). https://doi.org/10.1002/jmv.26259
doi: 10.1002/jmv.26259 pubmed: 32621617
L. Guo, S. Zhao, W. Li, Y. Wang, L. Li, S. Jiang et al. Absence of SARS-CoV-2 in semen of a COVID-19 patient cohort. Andrology 9(1), 42–47 (2021)
pubmed: 32598557 doi: 10.1111/andr.12848
M.M. Aboelnaga, A. Abdelrazek, N. Abdullah, M. El Shaer, Late impact of COVID-19 pneumonia on testosterone levels in recovered, post-hospitalized male patients. J. Endocrinol. Metab. 11(3–4), 76–82 (2021)
doi: 10.14740/jem749
M. Camici, P. Zuppi, P. Lorenzini, L. Scarnecchia, C. Pinnetti, S. Cicalini et al. Role of testosterone in SARS-CoV-2 infection: a key pathogenic factor and a biomarker for severe pneumonia. Int. J. Infect. Dis. 108, 244–251 (2021)
pubmed: 34023492 pmcid: 8135187 doi: 10.1016/j.ijid.2021.05.042
A. Salonia, M. Pontillo, P. Capogrosso, S. Gregori, M. Tassara, L. Boeri et al. Severely low testosterone in males with COVID-19: a case-control study. Andrology 9(4), 1043–1052 (2021)
pubmed: 33635589 pmcid: 8013327 doi: 10.1111/andr.12993
Y. Pazir, T. Eroglu, A. Kose, T.B. Bulut, C. Genc, M. Kadihasanoglu, Impaired semen parameters in patients with confirmed SARS-CoV-2 infection: a prospective cohort study. Andrologia 53(9), 1–6 (2021)
doi: 10.1111/and.14157
A. Sansone, D. Mollaioli, G. Ciocca, E. Colonnello, E. Limoncin, G. Balercia et al. “Mask up to keep it up”: preliminary evidence of the association between erectile dysfunction and COVID-19. Andrology 9(4), 1053–1059 (2021)
pubmed: 33742540 pmcid: 8250520 doi: 10.1111/andr.13003
A. Salonia, G. Corona, A. Giwercman, M. Maggi, S. Minhas, R.E. Nappi et al. SARS-CoV-2, testosterone and frailty in males (PROTEGGIMI): a multidimensional research project. Andrology 9(1), 19–22 (2021)
pubmed: 32369678 doi: 10.1111/andr.12811
M. Schroeder, B. Schaumburg, Z. Mueller, A. Parplys, D. Jarczak, K. Roedl et al. 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. 10(1), 1807–1818 (2021)
pubmed: 34402750 pmcid: 8451658 doi: 10.1080/22221751.2021.1969869
P. Gupta, A. Choudhary, G. Gopal, R. Kumar, A. Kumar, P. Tiwari et al. Detection of SARS-CoV2 virus using the real-time reverse transcriptase polymerase chain reaction in semen and seminal plasma from men with active COVID-19 infection—a pilot study. Indian J. Urol. 37(4), 331–334 (2021)
pubmed: 34759524 pmcid: 8555575 doi: 10.4103/iju.iju_117_21
R.E. Bridwell, D.R. Merrill, S.A. Griffith, J. Wray, J.J. Oliver, A coronavirus disease 2019 (COVID-19) patient with bilateral orchitis. Am. J. Emerg. Med. 42, 260.e3–260.e5 (2021)
pubmed: 32888763 doi: 10.1016/j.ajem.2020.08.068
A. La Marca, S. Busani, V. Donno, G. Guaraldi, G. Ligabue, M. Girardis, Testicular pain as an unusual presentation of COVID-19: a brief review of SARS-CoV-2 and the testis. Reprod. Biomed. Online 41(5), 903–906 (2020). https://doi.org/10.1016/j.rbmo.2020.07.017
doi: 10.1016/j.rbmo.2020.07.017 pubmed: 32826162 pmcid: 7377719
C. Ediz, H.H. Tavukcu, S. Akan, Y.E. Kizilkan, A. Alcin, K. Oz et al. Is there any association of COVID-19 with testicular pain and epididymo-orchitis? Int. J. Clin. Pr. 75(3), 1–5 (2021)
L.M. Mongioì, F. Barbagallo, R.A. Condorelli, R. Cannarella, A. Aversa, S. La Vignera et al. Possible long-term endocrine-metabolic complications in COVID-19: lesson from the SARS model. Endocrine 68(3), 467–470 (2020). https://doi.org/10.1007/s12020-020-02349-7
doi: 10.1007/s12020-020-02349-7 pubmed: 32488837 pmcid: 7266418
S. Wang, A. Zhang, Y. Pan, L. Liu, S. Niu, F. Zhang et al. Association between COVID-19 and male fertility: systematic review and meta-analysis of observational studies. World J. Mens. Health 40, 1–19 (2022)
G. Corona, W. Vena, A. Pizzocaro, F. Pallotti, D. Paoli, G. Rastrelli et al. Andrological effects of SARS-Cov-2 infection: a systematic review and meta-analysis. J. Endocrinol. Invest. 45(12), 2207–2219 (2022). https://doi.org/10.1007/s40618-022-01801-x
doi: 10.1007/s40618-022-01801-x pubmed: 35527294 pmcid: 9080963
Y. Xie, M. Mirzaei, M.S. Kahrizi, A.M. Shabestari, S.M. Riahi, M. Farsimadan et al. SARS-CoV-2 effects on sperm parameters: a meta-analysis study. J. Assist. Reprod. Genet. 39(7), 1555–1563 (2022). https://doi.org/10.1007/s10815-022-02540-x
doi: 10.1007/s10815-022-02540-x pubmed: 35716338 pmcid: 9206101
X. Chen, J. Ding, M. Liu, K. Xing, P. Ye, J. Min et al. A systemic review and meta-analysis of the effect of SARS-CoV-2 infection on sperm parameters. Research 2022, 1–13 (2022)
doi: 10.34133/2022/9835731
S.H. Russell, C.J. Small, S.A. Stanley, S. Franks, M.A. Ghatei, S.R. Bloom, The in vitro role of tumour necrosis factor-alpha and interleukin-6 in the hypothalamic-pituitary gonadal axis. J. Neuroendocrinol. 13(3), 296–301 (2001)
pubmed: 11207945 doi: 10.1046/j.1365-2826.2001.00632.x
H. Watanobe, Y. Hayakawa, Hypothalamic interleukin-1β and tumor necrosis factor-α, but not interleukin-6, mediate the endotoxin-induced suppression of the reproductive axis in rats. Endocrinology 144(11), 4868–4875 (2003)
pubmed: 12960020 doi: 10.1210/en.2003-0644
D.I. Spratt, J.R. Morton, R.S. Kramer, S.W. Mayo, C. Longcope, C.P.H. Vary, Increases in serum estrogen levels during major illness are caused by increased peripheral aromatization. Am. J. Physiol. Endocrinol. Metab. 291(3), 631–638 (2006)
doi: 10.1152/ajpendo.00467.2005
M. Watanabe, D. Caruso, D. Tuccinardi, R. Risi, M. Zerunian, M. Polici et al. Visceral fat shows the strongest association with the need of intensive care in patients with COVID-19. Metabolism 111, 154319 (2020). https://doi.org/10.1016/j.metabol.2020.154319
doi: 10.1016/j.metabol.2020.154319 pubmed: 32712222 pmcid: 7377788
R. Singh, S.S. Rathore, H. Khan, S. Karale, Y. Chawla, K. Iqbal et al. Association of obesity with COVID-19 severity and mortality: an updated systemic review, meta-analysis, and meta-regression. Front. Endocrinol. 13(Jun), 1–18 (2022)
F. Barbagallo, R.A. Condorelli, L.M. Mongioì, R. Cannarella, L. Cimino, M.C. Magagnini et al. Molecular mechanisms underlying the relationship between obesity and male infertility. Metabolites 11(12), 840 (2021). https://doi.org/10.3390/metabo11120840
doi: 10.3390/metabo11120840 pubmed: 34940598 pmcid: 8706114
S. La Vignera, R. Cannarella, F. Galvano, A. Grillo, A. Aversa, L. Cimino et al. The ketogenic diet corrects metabolic hypogonadism and preserves pancreatic ß-cell function in overweight/obese men: a single-arm uncontrolled study. Endocrine 72(2), 392–399 (2021). https://doi.org/10.1007/s12020-020-02518-8
doi: 10.1007/s12020-020-02518-8 pubmed: 33063272
L.M. Mongioì, L. Cimino, R.A. Condorelli, M.C. Magagnini, F. Barbagallo, R. Cannarella et al. Effectiveness of a very low calorie ketogenic diet on testicular function in overweight/obese men. Nutrients 12(10), 1–11 (2020)
doi: 10.3390/nu12102967
B. Kumar, M. Gopalakrishnan, M. Garg, P. Purohit, M. Banerjee, P. Sharma et al. Endocrine dysfunction among patients with COVID-19: a single-center experience from a tertiary hospital in India. Indian J. Endocrinol. Metab. 25(1), 14 (2021)
pubmed: 34386388 pmcid: 8323627 doi: 10.4103/ijem.IJEM_577_20
H.M. Al-Kuraishy, A.I. Al-Gareeb, M. Butnariu, G.E.S. Batiha, The crucial role of prolactin-lactogenic hormone in Covid-19. Mol. Cell Biochem. 477(5), 1381–1392 (2022). https://doi.org/10.1007/s11010-022-04381-9
doi: 10.1007/s11010-022-04381-9 pubmed: 35147901 pmcid: 8831165
I.E. Van Zeggeren, A. Boelen, D. Van De Beek, A.C. Heijboer, A.P.J. Vlaar, M.C. Brouwer, Sex steroid hormones are associated with mortality in COVID-19 patients: level of sex hormones in severe COVID-19. Medicine 100(34), E27072 (2021)
pubmed: 34449505 pmcid: 8389969 doi: 10.1097/MD.0000000000027072
D. Paoli, F. Pallotti, A. Anzuini, S. Bianchini, L. Caponecchia, A. Carraro et al. Male reproductive health after 3 months from SARS-CoV-2 infection: a multicentric study. J. Endocrinol. Invest. 46(1), 89–101 (2023). https://doi.org/10.1007/s40618-022-01887-3
doi: 10.1007/s40618-022-01887-3 pubmed: 35943723
B. Hu, K. Liu, Y. Ruan, X. Wei, Y. Wu, H. Feng et al. Evaluation of mid- and long-term impact of COVID-19 on male fertility through evaluating semen parameters. Transl. Androl. Urol. 11(2), 159–167 (2022)
pubmed: 35280660 pmcid: 8899150 doi: 10.21037/tau-21-922
S.K. Patel, M. Pathak, R. Sah, A. Kumar, Y.S. Malik, A.J. Rodríguez-Morales et al. Is sexual route a matter of concern for the SARS-CoV-2/COVID-19? Arch. Med. Res. 51(7), 745–746 (2020)
pubmed: 32586655 pmcid: 7290188 doi: 10.1016/j.arcmed.2020.06.008
L.J. Purpura, J. Alukal, A.M. Chong, L. Liu, A. Cantos, J. Shah et al. SARS-CoV-2 RNA shedding in semen and oligozoospermia of patient with severe coronavirus disease 11 weeks after infection. Emerg. Infect. Dis. 28(1), 196–200 (2022)
pubmed: 34647864 pmcid: 8714206 doi: 10.3201/eid2801.211521
B. Saylam, M. Uguz, M. Yarpuzlu, O. Efesoy, E. Akbay, S. Çayan, The presence of SARS-CoV-2 virus in semen samples of patients with COVID-19 pneumonia. Andrologia 53(8), e14145 (2021). https://doi.org/10.1111/and.14145
doi: 10.1111/and.14145 pubmed: 34115405 pmcid: 8420322
B. Machado, G.B. Barra, N. Scherzer, J. Massey, H. dos Santos Luz, R.H. Jacomo et al. Presence of SARS-CoV-2 RNA in semen—cohort study in the United States COVID-19 positive patients. Infect. Dis. Rep. 13(1), 96–101 (2021)
pubmed: 33557147 pmcid: 7930957 doi: 10.3390/idr13010012
D. Li, M. Jin, P. Bao, W. Zhao, S. Zhang, Clinical characteristics and results of semen tests among men with coronavirus disease 2019. JAMA Netw. Open 3(5), e208292 (2020)
pubmed: 32379329 pmcid: 7206502 doi: 10.1001/jamanetworkopen.2020.8292
D. Paoli, F. Pallotti, G. Nigro, L. Mazzuti, M.N. Hirsch, M.B. Valli et al. Molecular diagnosis of SARS-CoV-2 in seminal fluid. J. Endocrinol. Invest. 44(12), 2675–2684 (2021). https://doi.org/10.1007/s40618-021-01580-x
doi: 10.1007/s40618-021-01580-x pubmed: 33929709 pmcid: 8085093
M. Gacci, M. Coppi, E. Baldi, A. Sebastianelli, C. Zaccaro, S. Morselli et al. Semen impairment and occurrence of SARS-CoV-2 virus in semen after recovery from COVID-19. Hum. Reprod. 36(6), 1520–1529 (2021. https://academic.oup.com/humrep/article/36/6/1520/6125160
pubmed: 33522572 doi: 10.1093/humrep/deab026
A.N. Duarte-Neto, T.A. Teixeira, E.G. Caldini, C.T. Kanamura, M.S. Gomes-Gouvêa, A.B.G. dos Santos et al. Testicular pathology in fatal COVID-19: a descriptive autopsy study. Andrology 10(1), 13–23 (2022)
pubmed: 34196475 doi: 10.1111/andr.13073
M. Yang, S. Chen, B. Huang, J.M. Zhong, H. Su, Y.J. Chen et al. Pathological findings in the testes of COVID-19 patients: clinical implications. Eur. Urol. Focus 6(5), 1124–1129 (2020). https://doi.org/10.1016/j.euf.2020.05.009
doi: 10.1016/j.euf.2020.05.009 pubmed: 32563676 pmcid: 7261470
X. Ma, C. Guan, R. Chen, Y. Wang, S. Feng, R. Wang et al. Pathological and molecular examinations of postmortem testis biopsies reveal SARS-CoV-2 infection in the testis and spermatogenesis damage in COVID-19 patients. Cell Mol. Immunol. 18(2), 487–489 (2021). https://doi.org/10.1038/s41423-020-00604-5
doi: 10.1038/s41423-020-00604-5 pubmed: 33318629
J.K. Achua, K.Y. Chu, E. Ibrahim, K. Khodamoradi, K.S. Delma, O.A. Iakymenko et al. Histopathology and ultrastructural findings of fatal COVID-19 infections on testis. World J. Mens Health 39(1), 65–74 (2020)
pubmed: 33151050 pmcid: 7752514 doi: 10.5534/wjmh.200170
P. Dai, F. Qiao, Y. Chen, D.Y.L. Chan, H.C.H. Yim, K.L. Fok et al. SARS-CoV-2 and male infertility: from short- to long-term impacts. J. Endocrinol. Invest. 0123456789 (2023). https://doi.org/10.1007/s40618-023-02055-x
V. Nargund, Effects of psychological stress on male fertility. Nat. Rev. Urol. 12, 373–382 (2015)
pubmed: 26057063 doi: 10.1038/nrurol.2015.112
U. Seeland, F. Coluzzi, M. Simmaco, C. Mura, P.E. Bourne, M. Heiland et al. Evidence for treatment with estradiol for women with SARS-CoV-2 infection. BMC Med. 18(1), 1–9 (2020)
doi: 10.1186/s12916-020-01851-z
I.D. Harris, C. Fronczak, L. Roth, R.B. Meacham, Fertility and the aging male. Rev. Urol. 13(4), e184–e190 (2011. ; http://www.ncbi.nlm.nih.gov/pubmed/22232567%0A
pubmed: 22232567 pmcid: 3253726
V. Pino, A. Sanz, N. Valdés, J. Crosby, A. Mackenna, The effects of aging on semen parameters and sperm DNA fragmentation. J. Bras. Reprod. Assist. 24(1), 82–6 (2020)
R.A. Condorelli, S. La Vignera, F. Barbagallo, A. Alamo, L.M. Mongioì, R. Cannarella et al. Bio-functional sperm parameters: does age matter? Front. Endocrinol. 11, 1–7 (2020)
doi: 10.3389/fendo.2020.558374
G. Anifandis, C.I. Messini, M. Simopoulou, G. Sveronis, A. Garas, A. Daponte et al. SARS-CoV-2 vs. human gametes, embryos and cryopreservation. Syst. Biol. Reprod. Med. 67(4), 260–269 (2021). https://doi.org/10.1080/19396368.2021.1922537
doi: 10.1080/19396368.2021.1922537 pubmed: 34060390
F. Pan, X. Xiao, J. Guo, Y. Song, H. Li, D.P. Patel et al. No evidence of severe acute respiratory syndrome–coronavirus 2 in semen of males recovering from coronavirus disease 2019. Fertil. Steril. 113(6), 1135–1139 (2020). https://doi.org/10.1016/j.fertnstert.2020.04.024
doi: 10.1016/j.fertnstert.2020.04.024 pubmed: 32482249 pmcid: 7164916
F.M. Falahieh, M. Zarabadipour, M. Mirani, M. Abdiyan, M. DInparvar, H. Alizadeh et al. Effects of moderate COVID-19 infection on semen oxidative status and parameters 14 and 120 days after diagnosis. Reprod. Fertil. Dev. 33(12), 683–690 (2021)
pubmed: 34324827 doi: 10.1071/RD21153
No Title [Internet]. https://coronavirus.jhu.edu/data/mortality
V. Rago, A. Perri, SARS-CoV-2 infection and the male reproductive system: a brief review. Life (Basel). 13(2), 586 (2023). https://doi.org/10.3390/life13020586
doi: 10.3390/life13020586 pubmed: 36836943
A.P. Sharma, S. Sahoo, K. Goyal, A. Chandna, S. Kirubanandhan, V. Sharma et al. Absence of SARS-CoV-2 infection in the semen of men recovering from COVID-19 infection: an exploratory study and review of literature. Andrologia 53(8), 1–9 (2021)
doi: 10.1111/and.14136
C.A. Burke, A. Skytte, S. Kasiri, D. Howell, Z.P. Patel, M.P. Trolice, S.J. Parekattil, S.F. Michael, L.M. Paul, A cohort study of men infected with COVID-19 for presence of SARS-CoV-2 virus in their semen. J. Assist. Reprod. Genet.(2021). https://www.scopus.com/record/display.uri?eid=2-s2.0-85104904086&doi=10.1007%2Fs10815-021-02119-y&origin=inward&txGid=1330be3b9802f1195c6b50658042fbc2
D. Paoli, F. Pallotti, O. Turriziani, L. Mazzuti, G. Antonelli, A. Lenzi et al. SARS-CoV-2 presence in seminal fluid: myth or reality. Andrology 9(1), 23–26 (2021)
pubmed: 32453494 doi: 10.1111/andr.12825
B. Kayaaslan, G. Korukluoglu, I. Hasanoglu, A.K. Kalem, F. Eser, E. Akinci et al. Investigation of SARS-CoV-2 in semen of patients in the acute stage of COVID-19 infection. Urol. Int. 104(9–10), 678–683 (2020)
pubmed: 32781456 doi: 10.1159/000510531

Auteurs

Rossella Cannarella (R)

Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy. rossella.cannarella@phd.unict.it.
Glickman Urological & Kidney Institute, Cleveland Clinic Foundation, Cleveland, OH, USA. rossella.cannarella@phd.unict.it.

Marta Marino (M)

Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy.

Andrea Crafa (A)

Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy.

Vincenzo Bagnara (V)

Pediatric Surgery Unit, Policlinic G.B. Morgagni, Catania, Italy.

Sandro La Vignera (S)

Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy.

Rosita A Condorelli (RA)

Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy.

Aldo E Calogero (AE)

Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy.

Classifications MeSH