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Open Access 19-10-2022 | Fertility | Mini Review

COVID-19 and its treatments: lights and shadows on testicular function

Authors: Francesco Pallotti, Sandro C. Esteves, Fabiana Faja, Alessandra Buonacquisto, Anna Chiara Conflitti, Maria Neve Hirsch, Andrea Lenzi, Donatella Paoli, Francesco Lombardo

Published in: Endocrine | Issue 2/2023

Abstract

Purpose

The SARS-CoV-2 pandemic has rapidly spread worldwide and, among the others, the male gender was quickly recognized as an independent risk factor for both the disease and its consequences. Since the possibility of long-term hormonal axis changes and male gamete impairment have been hypothesized but a relatively low levels of evidence has been reached, we focused this narrative mini-review on summarizing key state-of-the-art knowledge on male reproductive effects of COVID-19 as a quick reference for reproductive health specialists.

Methods

A comprehensive Medline/PubMed and Embase search was performed selecting all relevant, peer-reviewed papers in English published from 2020. Other relevant papers were selected from the reference lists.

Results

Available evidence indicates that the likelihood of direct testicular damage from SARS-CoV-2 is somewhat low, but there are many indirect ways (fever, cytokine imbalance, and drugs) through which the pituitary-gonadal axis and spermatogenesis may be disrupted. These alterations are probably transient, but as available evidence is low quality, it cannot be excluded that previous pathologies or comorbidities might modulate the risk of their persistence. On the other hand, available evidence shows high safety regarding andrological health for available vaccines, although studies are mainly focused on mRNA vaccines.

Conclusion

A careful andrological evaluation of men recovering from COVID-19 is highly recommended. Since available evidence is relatively scarce, a careful andrological follow-up and counseling of these patients are mandatory.

WHO COVID-19 Dashboard. Geneva: World Health Organization, 2020. https://covid19.who.int/. Last accessed 3 Jue 2022

T. Haitao, J.V. Vermunt, J. Abeykoon, R. Ghamrawi, M. Gunaratne, M. Jayachandran, K. Narang, S. Parashuram, S. Suvakov, V.D. Garovic, COVID-19 and sex differences: mechanisms and biomarkers. Mayo Clin. Proc. 95(10), 2189–2203 (2020). https://doi.org/10.1016/j.mayocp.2020.07.024CrossRef

D. Paoli, F. Pallotti, A. Anzuini, S. Bianchini, L. Caponecchia, A. Carraro, M.R. Ciardi, F. Faja, C. Fiori, D. Gianfrilli, A. Lenzi, M. Lichtner, I. Marcucci, C.M. Mastroianni, G. Nigro, P. Pasculli, C. Pozza, F. Rizzo, P. Salacone, A. Sebastianelli, F. Lombardo, Male reproductive health after 3 months from SARS-CoV-2 infection: a multicentric study. J. Endocrinol. Investig. (2022) https://doi.org/10.1007/s40618-022-01887-3

G. Corona, W. Vena, A. Pizzocaro, F. Pallotti, D. Paoli, G. Rastrelli, E. Baldi, N. Cilloni, M. Gacci, F. Semeraro, A. Salonia, S. Minhas, R. Pivonello, A. Sforza, L. Vignozzi, A.M. Isidori, A. Lenzi, M. Maggi, F. Lombardo, Andrological effects of SARS-Cov-2 infection: a systematic review and meta-analysis. J. Endocrinol. Investig. (2022). https://doi.org/10.1007/s40618-022-01801-x.

D. Castanares-Zapatero, P. Chalon, L. Kohn, M. Dauvrin, J. Detollenaere, C. Maertens de Noordhout, C. Primus-de Jong, I. Cleemput, K. Van den Heede, Pathophysiology and mechanism of long COVID: a comprehensive review. Ann. Med. 54(1), 1473–1487 (2022). https://doi.org/10.1080/07853890.2022.2076901CrossRef

J. Aly, L. Choi, A.Y. Christy, The impact of coronavirus on reproduction: contraceptive access, pregnancy rates, pregnancy delay, and the role of vaccination. F. S. Rev. 3(3), 190–200 (2022). https://doi.org/10.1016/j.xfnr.2022.05.002CrossRef

H. Crook, S. Raza, J. Nowell, M. Young, P. Edison, Long covid-mechanisms, risk factors, and management. BMJ. 374, n1648 (2021) https://doi.org/10.1136/bmj.n1648. Erratum in: BMJ. 374, n1944 (2021)

O. Moreno-Perez, E. Merino, R. Alfayate, M.E. Torregrosa, M. Andres, J.M. Leon-Ramirez, V. Boix, J. Gil, A. Pico, COVID19-ALC Research group: male pituitary-gonadal axis dysfunction in post-acute COVID-19 syndrome-Prevalence and associated factors: a Mediterranean case series. Clin. Endocrinol. 96(3), 353–362 (2022). https://doi.org/10.1111/cen.14537CrossRef

S.A. Banihani, Human semen quality as affected by SARS-CoV-2 infection: mn up-to-date review. Andrologia 54(2), e14295 (2022). https://doi.org/10.1111/and.14295CrossRef

10.

M. Gao, C. Piernas, N.M. Astbury, J. Hippisley-Cox, S. O’Rahilly, P. Aveyard, S.A. Jebb, Associations between body-mass index and COVID-19 severity in 6·9 million people in England: a prospective, community-based, cohort study. Lancet Diabetes Endocrinol. 9(6), 350–359 (2021). https://doi.org/10.1016/S2213-8587(21)00089-9CrossRef

11.

N. Holman, P. Knighton, P. Kar, J. O’Keefe, M. Curley, A. Weaver, E. Barron, C. Bakhai, K. Khunti, N.J. Wareham, N. Sattar, B. Young, J. Valabhji, Risk factors for COVID-19-related mortality in people with type 1 and type 2 diabetes in England: a population-based cohort study. Lancet Diabetes Endocrinol. 8(10), 823–833 (2020). https://doi.org/10.1016/S2213-8587(20)30271-0CrossRef

12.

D. Paoli, F. Pallotti, G. Nigro, L. Mazzuti, M.N. Hirsch, M.B. Valli, S. Colangelo, C.M. Mastroianni, G. Antonelli, A. Lenzi, O. Turriziani, F. Lombardo, Molecular diagnosis of SARS-CoV-2 in seminal fluid. J. Endocrinol. Investig. 44(12), 2675–2684 (2021). https://doi.org/10.1007/s40618-021-01580-xCrossRef

13.

R. Rangu, P.L. Wander, B.M. Barrow, S. Zraika, Going viral in the islet: mediators of SARS-CoV-2 entry beyond ACE2. J. Mol. Endocrinol. JME-21-0282 (2022). https://doi.org/10.1530/JME-21-0282.

14.

B. Lin, C. Ferguson, J.T. White, S. Wang, R. Vessella, L.D. True, L. Hood, P.S. Nelson, Prostate-localized and androgen-regulated expression of the membrane-bound serine protease TMPRSS2. Cancer Res. 59(17), 4180–4184 (1999)

15.

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.2020.05.001CrossRef

16.

L. Pascolo, G. Zito, L. Zupin, S. Luppi, E. Giolo, M. Martinelli, D. De Rocco, S. Crovella, G. Ricci, Renin angiotensin system, COVID-19 and male fertility: any risk for conceiving? Microorganisms 8(10), 1492 (2020). https://doi.org/10.3390/microorganisms8101492CrossRef

17.

A.N. Duarte-Neto, T.A. Teixeira, E.G. Caldini, C.T. Kanamura, M.S. Gomes-Gouvêa, A.B.G. Dos Santos, R.A.A. Monteiro, J.R.R. Pinho, T. Mauad, L.F.F. da Silva, P.H.N. Saldiva, M. Dolhnikoff, K.R.M. Leite, J. Hallak, Testicular pathology in fatal COVID-19: a descriptive autopsy study. Andrology 10(1), 13–23 (2022). https://doi.org/10.1111/andr.13073CrossRef

18.

J.K. Achua, K.Y. Chu, E. Ibrahim, K. Khodamoradi, K.S. Delma, O.A. Iakymenko, O.N. Kryvenko, H. Arora, R. Ramasamy, Histopathology and ultrastructural findings of fatal COVID-19 infections on testis. World J. Mens. Health 39(1), 65–74 (2021). https://doi.org/10.5534/wjmh.200170CrossRef

19.

T. Peirouvi, A. Aliaghaei, B. Eslami Farsani, S. Ziaeipour, V. Ebrahimi, M. Forozesh, M. Ghadipasha, G.R. Mahmoudiasl, A. Aryan, N. Moghimi, S. Abdi, A. Raoofi, M. Kargar Godaneh, M.A. Abdollahifar, COVID-19 disrupts the blood-testis barrier through the induction of inflammatory cytokines and disruption of junctional proteins. Inflamm. Res. 70(10-12), 1165–1175 (2021). https://doi.org/10.1007/s00011-021-01497-4CrossRef

20.

G.M. Bwire, M.V. Majigo, B.J. Njiro, A. Mawazo, Detection profile of SARS-CoV-2 using RT-PCR in different types of clinical specimens: a systematic review and meta-analysis. J. Medm Virol. 93(2), 719–725 (2021). https://doi.org/10.1002/jmv.26349CrossRef

21.

C. Ediz, H.H. Tavukcu, S. Akan, Y.E. Kizilkan, A. Alcin, K. Oz, O. Yilmaz, Is there any association of COVID-19 with testicular pain and epididymo-orchitis? Intm J. Clin. Pract. 75(3), e13753 (2021)

22.

S. Aslan, U. Eryuruk, Necrotizing Orchitis due to COVİD-19. Rev. Soc. Bras. Med Trop. 54, e04082021 (2021)CrossRef

23.

G. Corona, E. Baldi, A.M. Isidori, D. Paoli, F. Pallotti, L. De Santis, F. Francavilla, S. La Vignera, R. Selice, L. Caponecchia, R. Pivonello, A. Ferlin, C. Foresta, E.A. Jannini, A. Lenzi, M. Maggi, F. Lombardo, SARS-CoV-2 infection, male fertility and sperm cryopreservation: a position statement of the Italian Society of Andrology and Sexual Medicine (SIAMS) (Società Italiana di Andrologia e Medicina della Sessualità). J. Endocrinol. Investig. 43(8), 1153–1157 (2020). https://doi.org/10.1007/s40618-020-01290-wCrossRef

24.

J. Xu, L. Qi, X. Chi et al. Orchitis: a complication of severe acute respiratory syndrome (SARS). Biol. Reprod. 74, 410–416 (2006)CrossRef

25.

F. Pan, X. Xiao, J. Guo, Y. Song, H. Li, D.P. Patel, A.M. Spivak, J.P. Alukal, X. Zhang, C. Xiong, P.S. Li, J.M. Hotaling, 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.2020.04.024CrossRef

26.

H. Li, X. Xiao, J. Zhang, M.I. Zafar, C. Wu, Y. Long, W. Lu, F. Pan, T. Meng, K. Zhao, L. Zhou, S. Shen, L. Liu, Q. Liu, C. Xiong, Impaired spermatogenesis in COVID-19 patients. EClinicalMedicine 28, 100604 (2020). https://doi.org/10.1016/j.eclinm.2020.100604CrossRef

27.

N. Delli Muti, F. Finocchi, G. Tossetta, G. Salvio, M. Cutini, D. Marzioni, G. Balercia, Could SARS-CoV-2 infection affect male fertility and sexuality? APMIS 130(5), 243–252 (2022). https://doi.org/10.1111/apm.13210.CrossRef

28.

Y. He, J. Wang, J. Ren, Y. Zhao, J. Chen, X. Chen, Effect of COVID-19 on male reproductive system - a systematic review. Front Endocrinol. 12, 677701 (2021). https://doi.org/10.3389/fendo.2021.677701CrossRef

29.

E. Carlsen, A.M. Andersson, J.H. Petersen, N.E. Skakkebaek, History of febrile illness and variation in semen quality. Hum. Reprod. 18(10), 2089–2092 (2003). https://doi.org/10.1093/humrep/deg412CrossRef

30.

M. Sergerie, R. Mieusset, F. Croute, M. Daudin, L. Bujan, High risk of temporary alteration of semen parameters after recent acute febrile illness. Fertil. Steril. 88(4), 970.e1-7 (2007). https://doi.org/10.1016/j.fertnstert.2006.12.045CrossRef

31.

D. Durairajanayagam, A. Agarwal, C. Ong, Causes, effects and molecular mechanisms of testicular heat stress. Reprod. Biomed. Online 30(1), 14–27 (2015). https://doi.org/10.1016/j.rbmo.2014.09.018CrossRef

32.

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). https://doi.org/10.1093/qjmed/hcab028CrossRef

33.

N. Holtmann, P. Edimiris, M. Andree, C. Doehmen, D. Baston-Buest, O. Adams, J.S. Kruessel, A.P. Bielfeld, Assessment of SARS-CoV-2 in human semen-a cohort study. Fertil. Steril. 114(2), 233–238 (2020). https://doi.org/10.1016/j.fertnstert.2020.05.028CrossRef

34.

M. Gacci, M. Coppi, E. Baldi, A. Sebastianelli, C. Zaccaro, S. Morselli, A. Pecoraro, A. Manera, R. Nicoletti, A. Liaci, C. Bisegna, L. Gemma, S. Giancane, S. Pollini, A. Antonelli, F. Lagi, S. Marchiani, S. Dabizzi, S. Degl’Innocenti, F. Annunziato, M. Maggi, L. Vignozzi, A. Bartoloni, G.M. Rossolini, S. Serni, Semen impairment and occurrence of SARS-CoV-2 virus in semen after recovery from COVID-19. Hum. Reprod. 36(6), 1520–1529 (2021). https://doi.org/10.1093/humrep/deab026CrossRef

35.

B. Hajizadeh Maleki, B. Tartibian, COVID-19 and male reproductive function: a prospective, longitudinal cohort study. Reproduction 161(3), 319–331 (2021). https://doi.org/10.1530/REP-20-0382CrossRef

36.

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. 23(5), 479–483 (2021). https://doi.org/10.4103/aja.aja_31_21CrossRef

37.

G. Erbay, A. Sanli, H. Turel, U. Yavuz, A. Erdogan, M. Karabakan, M. Yaris, M.H. Gultekin, Short-term effects of COVID-19 on semen parameters: a multicenter study of 69 cases. Andrology 9(4), 1060–1065 (2021). https://doi.org/10.1111/andr.13019CrossRef

38.

A. Gul, S. Zengin, G. Dundar, M. Ozturk, Do SARS-CoV-2 infection (COVID-19) and the medications administered for its treatment impair testicular functions? Urol. Int. 105(11-12), 944–948 (2021). https://doi.org/10.1159/000517925CrossRef

39.

L. Ma, W. Xie, D. Li, L. Shi, G. Ye, Y. Mao, Y. Xiong, H. Sun, F. Zheng, Z. Chen, J. Qin, J. Lyu, Y. Zhang, M. Zhang, 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.26259CrossRef

40.

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), e14157 (2021). https://doi.org/10.1111/and.14157CrossRef

41.

Y. Ruan, B. Hu, Z. Liu, K. Liu, H. Jiang, H. Li, R. Li, Y. Luan, X. Liu, G. Yu, S. Xu, X. Yuan, S. Wang, W. Yang, Z. Ye, J. Liu, T. Wang, 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). https://doi.org/10.1111/andr.12939CrossRef

42.

G.G.G. Donders, E. Bosmans, J. Reumers, F. Donders, J. Jonckheere, G. Salembier, N. Stern, Y. Jacquemyn, W. Ombelet, C.E. Depuydt, Sperm quality and absence of SARS-CoV-2 RNA in semen after COVID-19 infection: a prospective, observational study and validation of the SpermCOVID test. Fertil. Steril. 117(2), 287–296 (2022). https://doi.org/10.1016/j.fertnstert.2021.10.022CrossRef

43.

H.C. Schuppe, A. Meinhardt, Immune privilege and inflammation of the testis. Chem. Immunol. Allergy 88, 1–14 (2005). https://doi.org/10.1159/000087816CrossRef

44.

Y.D. Gao, M. Ding, X. Dong, J.J. Zhang, A. Kursat Azkur, D. Azkur, H. Gan, Y.L. Sun, W. Fu, W. Li, H.L. Liang, Y.Y. Cao, Q. Yan, C. Cao, H.Y. Gao, M.C. Brüggen, W. van de Veen, M. Sokolowska, M. Akdis, C.A. Akdis, Risk factors for severe and critically ill COVID-19 patients: a review. Allergy 76(2), 428–455 (2021). https://doi.org/10.1111/all.14657CrossRef

45.

M. Fraczek, M. Kurpisz, Cytokines in the male reproductive tract and their role in infertility disorders. J. Reprod. Immunol. 108, 98–104 (2015). https://doi.org/10.1016/j.jri.2015.02.001CrossRef

46.

M.W. Li, W. Xia, D.D. Mruk, C.Q. Wang, H.H. Yan, M.K. Siu, W.Y. Lui, W.M. Lee, C.Y. Cheng, Tumor necrosis factor {alpha} reversibly disrupts the blood-testis barrier and impairs Sertoli-germ cell adhesion in the seminiferous epithelium of adult rat testes. J. Endocrinol. 190(2), 313–329 (2006). https://doi.org/10.1677/joe.1.06781CrossRef

47.

O. Sarkar, P.P. Mathur, C.Y. Cheng, D.D. Mruk, Interleukin 1 alpha (IL1A) is a novel regulator of the blood-testis barrier in the rat. Biol. Reprod. 78(3), 445–454 (2008). https://doi.org/10.1095/biolreprod.107.064501CrossRef

48.

C.V. Pérez, E.H. Pellizzari, S.B. Cigorraga, M.N. Galardo, M. Naito, L. Lustig, P.V. Jacobo, IL17A impairs blood-testis barrier integrity and induces testicular inflammation. Cell Tissue Res 358(3), 885–898 (2014). https://doi.org/10.1007/s00441-014-1995-5CrossRef

49.

M.E. Ferreiro, M.S. Amarilla, L. Glienke, C.S. Méndez, C. González, P.V. Jacobo, C.M. Sobarzo, A. De Laurentiis, M.J. Ferraris, M.S. Theas, The inflammatory mediators TNFα and nitric oxide arrest spermatogonia GC-1 cell cycle. Reprod. Biol. 19(4), 329–339 (2019). https://doi.org/10.1016/j.repbio.2019.11.001CrossRef

50.

Y. Fang, Y. Su, J. Xu, Z. Hu, K. Zhao, C. Liu, H. Zhang, Varicocele-mediated male infertility: from the perspective of testicular immunity and inflammation. Front. Immunol. 12, 729539 (2021). https://doi.org/10.3389/fimmu.2021.729539CrossRef

51.

J. Xu, L. He, Y. Zhang, Z. Hu, Y. Su, Y. Fang, M. Peng, Z. Fan, C. Liu, K. Zhao, H. Zhang, Severe acute respiratory syndrome coronavirus 2 and male reproduction: relationship, explanations, and clinical remedies. Front Physiol. 12, 651408 (2021). https://doi.org/10.3389/fphys.2021.651408CrossRef

52.

D. Paoli, B. Gilio, E. Piroli, M. Gallo, F. Lombardo, F. Dondero, A. Lenzi, L. Gandini, Testicular tumors as a possible cause of antisperm autoimmune response. Fertil. Steril. 91(2), 414–419 (2009). https://doi.org/10.1016/j.fertnstert.2007.11.084CrossRef

53.

D. Cui, G. Han, Y. Shang, C. Liu, L. Xia, L. Li, S. Yi, Antisperm antibodies in infertile men and their effect on semen parameters: a systematic review and meta-analysis. Clin. Chim. Acta 444, 29–36 (2015). https://doi.org/10.1016/j.cca.2015.01.033CrossRef

54.

S. Morselli, A. Sebastianelli, A. Liaci, C. Zaccaro, A. Pecoraro, R. Nicoletti, A. Manera, C. Bisegna, R. Campi, S. Pollini, A. Antonelli, F. Lagi, M. Coppi, E. Baldi, S. Marchiani, S. Nicolò, M. Torcia, F. Annunziato, M. Maggi, L. Vignozzi, A. Bartoloni, G.M. Rossolini, S. Serni, M. Gacci, Male reproductive system inflammation after healing from coronavirus disease 2019. Andrology (2021) https://doi.org/10.1111/andr.13138.

55.

G. Rastrelli, V. Di Stasi, F. Inglese, M. Beccaria, M. Garuti, D. Di Costanzo, F. Spreafico, G.F. Greco, G. Cervi, A. Pecoriello, A. Magini, T. Todisco, S. Cipriani, E. Maseroli, G. Corona, A. Salonia, A. Lenzi, M. Maggi, G. De Donno, L. Vignozzi, Low testosterone levels predict clinical adverse outcomes in SARS-CoV-2 pneumonia patients. Andrology 9(1), 88–98 (2021). https://doi.org/10.1111/andr.12821CrossRef

56.

A. Salonia, M. Pontillo, P. Capogrosso, S. Gregori, M. Tassara, L. Boeri, C. Carenzi, C. Abbate, D. Cignoli, A.M. Ferrara, W. Cazzaniga, I. Rowe, G.A. Ramirez, C. Tresoldi, J. Mushtaq, M. Locatelli, L. Santoleri, A. Castagna, A. Zangrillo, F. De Cobelli, M. Tresoldi, G. Landoni, P. Rovere-Querini, F. Ciceri, F. Montorsi, Severely low testosterone in males with COVID-19: a case-control study. Andrology 9(4), 1043–1052 (2021). https://doi.org/10.1111/andr.12993CrossRef

57.

A. Salonia, M. Pontillo, P. Capogrosso, S. Gregori, C. Carenzi, A.M. Ferrara, I. Rowe, L. Boeri, A. Larcher, G.A. Ramirez, C. Tresoldi, M. Locatelli, G. Cavalli, L. Dagna, A. Castagna, A. Zangrillo, M. Tresoldi, G. Landoni, P. Rovere-Querini, F. Ciceri, F. Montorsi, Testosterone in males with COVID-19: a 7-month cohort study. Andrology 10(1), 34–41 (2022). https://doi.org/10.1111/andr.13097CrossRef

58.

M. Semet, M. Paci, J. Saïas-Magnan, C. Metzler-Guillemain, R. Boissier, H. Lejeune, J. Perrin, The impact of drugs on male fertility: a review. Andrology 5(4), 640–663 (2017). https://doi.org/10.1111/andr.12366CrossRef

59.

M.J. Vincent, E. Bergeron, S. Benjannet, B.R. Erickson, P.E. Rollin, T.G. Ksiazek, N.G. Seidah, S.T. Nichol, Chloroquine is a potent inhibitor of SARS coronavirus infection and spread. Virol. J. 2, 69 (2005). https://doi.org/10.1186/1743-422X-2-69CrossRef

60.

S. Satarker, T. Ahuja, M. Banerjee, E.V.B. Dogra, S. Agarwal, T. Nampoothiri, M. Hydroxychloroquine, in COVID-19: potential mechanism of action against SARS-CoV-2. Curr. Pharmacol. Rep. 6(5), 203–211 (2020). https://doi.org/10.1007/s40495-020-00231-8CrossRef

61.

M. Sainz-Gil, N. Merino Kolly, V. Velasco-González, Z. Verde Rello, A.M. Fernandez-Araque, R. Sanz Fadrique, L.H. Martín Arias, Hydroxychloroquine safety in Covid-19 vs non-Covid-19 patients: analysis of differences and potential interactions. Expert Opin. Drug Saf. (2022). https://doi.org/10.1080/14740338.2022.2078303

62.

E. Fallani, F. Cevenini, P.E. Lazzerini, A. Verdini, S. Saponara, Off-label use of hydroxychloroquine in COVID-19: analysis of reports of suspected adverse reactions from the Italian National Network of Pharmacovigilance. J. Clin. Pharmacol. 62(5), 646–655 (2022). https://doi.org/10.1002/jcph.2006CrossRef

63.

S. Vita, D. Forliano, A. De Luca, A. Beccacece, L. Marchioni, E. Nicastri; On Behalf Of The Covid-Inmi Study Group, Drug policies skyline during COVID-19 pandemic. J. Clin. Med. 10(14), 3117 (2021). https://doi.org/10.3390/jcm10143117CrossRef

64.

W.G. Nicola, M.I. Khayria, M.M. Osfor, Plasma testosterone level and the male genital system after chloroquine therapy. Boll. Chim. Farm. 136(1), 39–43 (1997)

65.

B.C. Tiseo, E. Bonfá, E.F. Borba, G.A. Munhoz, G. Wood, M. Srougi, C.A. Silva, M. Cocuzza, Complete urological evaluation including sperm DNA fragmentation in male systemic lupus erythematosus patients. Lupus 28(1), 59–65 (2019). https://doi.org/10.1177/0961203318815764CrossRef

66.

B.L. Bermas, Paternal safety of anti-rheumatic medications. Best. Pract. Res. Clin. Obstet. Gynaecol. 64, 77–84 (2020). https://doi.org/10.1016/j.bpobgyn.2019.09.004CrossRef

67.

V. Savasi, F. Parisi, M. Oneta, A. Laoreti, B. Parrilla, P. Duca, I. Cetin, Effects of highly active antiretroviral therapy on semen parameters of a cohort of 770 HIV-1 infected men. PLoS ONE 14(2), e0212194 (2019). https://doi.org/10.1371/journal.pone.0212194CrossRef

68.

O.A. Adaramoye, O.O. Akanni, O.M. Adewumi, S.E. Owumi, Lopinavir/Ritonavir, an antiretroviral drug, lowers sperm quality and induces testicular oxidative damage in rats. Tokai J. Exp. Clin. Med. 40(2), 51–57 (2015)

69.

M.A. Lopez-Ruz, P. Navas, M.A. López-Zúñiga, M.C. Gonzalvo, A. Sampedro, J. Pasquau, C. Hidalgo-Tenorio, R. Javier, J.A. Castilla, Effect of monotherapy with darunavir/ritonavir on viral load in seminal fluid, and quality parameters of semen in HIV-1-positive patients. PLoS ONE 11(7), e0159305 (2016). https://doi.org/10.1371/journal.pone.0159305CrossRef

70.

M.A. López-Ruz, M.A. López-Zúñiga, M.C. Gonzalvo, A. Sampedro, J. Pasquau, C. Hidalgo, J. Rosario, J.A. Castilla, Effect of monotherapy with darunavir/cobicistat on viral load and semen quality of HIV-1 patients. PLoS ONE 13(4), e0196257 (2018). https://doi.org/10.1371/journal.pone.0196257CrossRef

71.

R. Gutierrez, H. Mendez-Figueroa, J.G. Biebighauser, A. Bhalwal, B.L. Pineles, S.P. Chauhan, Remdesivir use in pregnancy during the SARS-CoV-2 pandemic. J. Matern Fetal Neonatal Med 15, 1–7 (2022). https://doi.org/10.1080/14767058.2022.2041595CrossRef

72.

S. Masyeni, M. Iqhrammullah, A. Frediansyah, F. Nainu, T. Tallei, T.B. Emran, Y. Ophinni, K. Dhama, H. Harapan, Molnupiravir: a lethal mutagenic drug against rapidly mutating severe acute respiratory syndrome coronavirus 2-A narrative review. J. Med. Virol. (2022). https://doi.org/10.1002/jmv.27730.

73.

Therapeutics and COVID-19: living guideline, 22 April 2022 (World Health Organization, Geneva, 2022). Last accessed 17 May 2022

74.

M. Huleihel, E. Lunenfeld, A. Levy, G. Potashnik, M. Glezerman, Distinct expression levels of cytokines and soluble cytokine receptors in seminal plasma of fertile and infertile men. Fertil. Steril. 66(1), 135–139 (1996)CrossRef

75.

J.A. Politch, L. Tucker, F.P. Bowman, D.J. Anderson, Concentrations and significance of cytokines and other immunologic factors in semen of healthy fertile men. Hum. Reprod. 22(11), 2928–2935 (2007). https://doi.org/10.1093/humrep/dem281CrossRef

76.

M. Imamoğlu, S.S. Bülbül, N. Kaklikkaya, H. Sarihan, Oxidative, inflammatory and immunologic status in children with undescended testes. Pediatr. Int 54(6), 816–819 (2012). https://doi.org/10.1111/j.1442-200X.2012.03695.xCrossRef

77.

R. Castiglione, M. Salemi, L.O. Vicari, E. Vicari, Relationship of semen hyperviscosity with IL-6, TNF-α, IL-10 and ROS production in seminal plasma of infertile patients with prostatitis and prostato-vesiculitis. Andrologia 46(10), 1148–1155 (2014). https://doi.org/10.1111/and.12207CrossRef

78.

R. Finelli, F. Pallotti, F. Cargnelutti, F. Faja, T. Carlini, F. Rizzo, A. Lenzi, D. Paoli, F. Lombardo, D.N.A. Sperm, damage and cytokines in varicocele: a case-control study. Andrologia 53(5), e14023 (2021). https://doi.org/10.1111/and.14023CrossRef

79.

H. Hasan, S. Bhushan, M. Fijak, A. Meinhardt, Mechanism of inflammatory associated impairment of sperm function, spermatogenesis and steroidogenesis. Front. Endocrinol. 13, 897029 (2022). https://doi.org/10.3389/fendo.2022.897029CrossRef

80.

81.

B.L. Bermas, Paternal safety of anti-rheumatic medications. Best. Pract. Res Clin. Obstet. Gynaecol. 64, 77–84 (2020). https://doi.org/10.1016/j.bpobgyn.2019.09.004CrossRef

82.

F. Castinetti, T. Brue, Impact of Cushing’s syndrome on fertility and pregnancy. Ann Endocrinol. (2022). https://doi.org/10.1016/j.ando.2022.04.001

83.

M. Orazizadeh, L.S. Khorsandi, M. Hashemitabar, Toxic effects of dexamethasone on mouse testicular germ cells. Andrologia 42(4), 247–253 (2010). https://doi.org/10.1111/j.1439-0272.2009.00985.xCrossRef

84.

P. Zou, X. Wang, W. Yang, C. Liu, Q. Chen, H. Yang, N. Zhou, Y. Zeng, H. Chen, G. Zhang, J. Liu, J. Cao, L. Ao, L. Sun, Mechanisms of stress-induced spermatogenesis impairment in male rats following unpredictable chronic mild Stress (uCMS). Int. J. Mol. Sci. 20(18), 4470 (2019). https://doi.org/10.3390/ijms20184470CrossRef

85.

L. Ren, Y. Zhang, Y. Xin, G. Chen, X. Sun, Y. Chen, B. He, Dysfunction in Sertoli cells participates in glucocorticoid-induced impairment of spermatogenesis. Mol. Reprod. Dev. 88(6), 405–415 (2021). https://doi.org/10.1002/mrd.23515CrossRef

86.

J.G. Mogilner, Y. Elenberg, M. Lurie, E. Shiloni, A.G. Coran, I. Sukhotnik, Effect of dexamethasone on germ cell apoptosis in the contralateral testis after testicular ischemia-reperfusion injury in the rat. Fertil. Steril. 85(Suppl 1), 1111–1117 (2006). https://doi.org/10.1016/j.fertnstert.2005.10.021CrossRef

87.

R. Hazra, D. Upton, M. Jimenez, R. Desai, D.J. Handelsman, C.M. Allan, In vivo actions of the Sertoli cell glucocorticoid receptor. Endocrinology 155(3), 1120–1130 (2014). https://doi.org/10.1210/en.2013-1940CrossRef

88.

J.M. Holst, E. Horváth-Puhó, R.B. Jensen, M. Rix, K. Kristensen, N.T. Hertel, O.M. Dekkers, H.T. Sørensen, A. Juul, J.O.L. Jørgensen, Cushing’s syndrome in children and adolescents: a Danish nationwide population-based cohort study. Eur. J. Endocrinol. 176(5), 567–574 (2017). https://doi.org/10.1530/EJE-16-0843CrossRef

89.

N. Reisch, L. Flade, M. Scherr, M. Rottenkolber, F. Pedrosa Gil, M. Bidlingmaier, H. Wolff, H.P. Schwarz, M. Quinkler, F. Beuschlein, M. Reincke, High prevalence of reduced fecundity in men with congenital adrenal hyperplasia. J. Clin. Endocrinol. Metab. 94(5), 1665–1670 (2009). https://doi.org/10.1210/jc.2008-1414CrossRef

90.

P. Diaz, P. Reddy, R. Ramasahayam, M. Kuchakulla, R. Ramasamy, COVID-19 vaccine hesitancy linked to increased internet search queries for side effects on fertility potential in the initial rollout phase following Emergency Use Authorization. Andrologia 53(9), e14156 (2021). https://doi.org/10.1111/and.14156CrossRef

91.

D.C. Gonzalez, D.E. Nassau, K. Khodamoradi, E. Ibrahim, R. Blachman-Braun, J. Ory, R. Ramasamy, Sperm parameters before and after COVID-19 mRNA vaccination. JAMA 326(3), 273–274 (2021). https://doi.org/10.1001/jama.2021.9976CrossRef

92.

M. Safrai, S. Herzberg, T. Imbar, B. Reubinoff, U. Dior, A. Ben-Meir, The BNT162b2 mRNA Covid-19 vaccine does not impair sperm parameters. Reprod. Biomed. Online 44(4), 685–688 (2022). https://doi.org/10.1016/j.rbmo.2022.01.008CrossRef

93.

H. Zhu, X. Wang, F. Zhang, Y. Zhu, M.R. Du, Z.W. Tao, C. Sun, H.T. Ma, Y.D. Li, G.Q. Liang, J. Ren J., Feng, F. Jiang, Evaluation of inactivated COVID-19 vaccine on semen parameters in reproductive-age males: a retrospective cohort study. Asian J. Androl. (2022) https://doi.org/10.4103/aja202225

94.

S. Olana, R. Mazzilli, G. Salerno, V. Zamponi, M.G. Tarsitano, M. Simmaco, D. Paoli, A. Faggiano, 4BNT162b2 mRNA COVID-19 vaccine and semen: What do we know? Andrology 10(6), 1023–1029 (2022). https://doi.org/10.1111/andr.13199CrossRef

Title: COVID-19 and its treatments: lights and shadows on testicular function
Authors: Francesco Pallotti
Sandro C. Esteves
Fabiana Faja
Alessandra Buonacquisto
Anna Chiara Conflitti
Maria Neve Hirsch
Andrea Lenzi
Donatella Paoli
Francesco Lombardo
Publication date: 19-10-2022
Publisher: Springer US
Keywords: Fertility
Ritonavir
SARS-CoV-2
COVID-19
Cytokines
Published in: Endocrine / Issue 2/2023
Print ISSN: 1355-008X
Electronic ISSN: 1559-0100
DOI: https://doi.org/10.1007/s12020-022-03221-6

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