Relationship of semen quality and reproductive hormones with susceptibility to COVID-19 infection

Relationship of semen quality and reproductive hormones with susceptibility to COVID-19 infection | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Relationship of semen quality and reproductive hormones with susceptibility to COVID-19 infection Yasar PAZIR, Huseyin Kocan, Haydar Guler, Taha Burak Bulut, Huseyin Besiroglu, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3964500/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background and Aim: There is increasing evidence that semen quality reflects the overall health status of individuals and is a marker of future health. In addition, reproductive hormones have significant regulatory effects on the immune system and the function of inflammatory cells. In this study, it was aimed to investigate whether baseline semen quality and serum reproductive hormone levels are potential indicators of susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Methods: The medical records of a total of 1303 patients who underwent semen analysis and hormonal evaluation including total testosterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin (PRL for infertility or other medical reasons were retrospectively analyzed. Among these patients, 316 were determined to have previously been exposed to SARS-CoV-2 infection. Results: There was no statistically significant difference in baseline hormone profile (FSH, LH, PRL, and total testosterone) and semen parameters between patients exposed to SARS-CoV-2 infection and non-exposed patients. Conclusions : This study demonstrated that baseline semen quality and serum reproductive hormone levels (total testosterone, PRL, FSH, and LH) are not indicators of susceptibility to SARS-CoV-2 infection. semen quality hormone susceptibility SARS-CoV-2 COVID-19 BACKGROUND A novel beta-coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread rapidly worldwide and caused the coronavirus disease 2019 (COVID-19) pandemic ( 1 ). Since it was first identified in China in December 2019, more than 767,750,000 cases of COVID-19 have been reported worldwide as of June 2023 ( 2 ). Clinical studies have demonstrated that comorbidities such as hypertension, diabetes, dyslipidemia, and obesity weaken the immune system through various mechanisms, increase the susceptibility of individuals to COVID-19, and worsen the prognosis of the disease ( 3 , 4 ). There is increasing evidence that semen quality reflects the overall health status of individuals and is a marker of future health ( 5 – 8 ). Various studies have indicated that infertile men have a higher rate of comorbidities than fertile men ( 6 , 9 ). In addition, poor semen parameters and male infertility have been shown to be an early indicator of an increased risk of cardiovascular disease, diabetes, hyperlipidemia, cancer, and even overall mortality ( 9 – 14 ). Although the link between male reproductive health and somatic health has not been fully elucidated, it is suggested that genetic, hormonal, environmental and epigenetic factors play a role in this relationship ( 8 ). Moreover, comorbidities may directly impair male reproductive function ( 15 ). Therefore, it has been hypothesized that semen analysis may serve as a potential biomarker for overall health counseling, such as potential preventive health measures and chronic disease management, beyond fertility counseling. SARS-CoV-2 infects the host via angiotensin converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) expressed in different tissues such as lung, heart, testis, prostate and kidney ( 16 ). The transcription of the TMPRSS2 and ACE2 genes is regulated by the androgen receptor ( 17 ). It has been shown that suppression of androgen hormones causes a decrease in ACE2 expression and activity ( 18 ). In addtion, reproductive hormones have significant regulatory effects on the immune system and the function of inflammatory cells ( 19 ). Testosterone increases the susceptibility to both viral and bacterial infections by suppressing the adaptive and innate immune system ( 20 ). In contrast, prolactin (PRL) plays a key role in stimulating both innate and adaptive immunity ( 21 , 22 ). It has been reported that hypoprolactinemia may even cause death due to opportunistic infections ( 23 ). These findings suggest that the hormonal status of individuals might play an important role in susceptibility to COVID-19 and severity of clinical course. In the present study, it was aimed to investigate whether baseline semen quality and serum reproductive hormone levels are potential indicators of susceptibility to SARS-CoV-2 infection. PATIENTS AND METHODS Study design and population The medical records of patients who underwent semen analysis and hormonal evaluation due to couple's infertility or other medical reasons in a tertiary center between January 2020 and January 2022 were retrospectively analyzed. Men between the ages of 18–49 were included in the study. Before semen analysis and hormonal evaluation, patients who (i) had a history of COVID-19 disease and (ii) were previously exposed to treatments that could affect the basal parameters of patients such as gonadotropins, antioxidants, anti-estrogens and testosterone replacement were excluded from the study. A total of 1303 patients met the study criteria. Among these patients, those previously exposed to SARS-CoV-2 infection were identified through reverse transcription-polymerase chain reaction (RT-PCR) test of pharyngeal and nasal swab samples and/or the detection of typical COVID-19 pneumonia (ground glass opacities and consolidation areas especially in the peripheral and lower lobes) on chest imaging in their medical records. All procedures performed in this study involving human participants were in accordance with the Declaration of Helsinki (as revised in 2013). The present study protocol was reviewed and approved by the institutional review board. Semen analysis Semen samples were collected by masturbation after three days of abstinence and analyzed within the first hour after ejaculation by the experienced andrology laboratory staff. Semen volume, sperm concentration, motility and morphology of each case were determined in accordance with the recommendations of the WHO 2010 laboratory manual for the examination and processing of human semen (5th edition). The patients were categorized as those whose semen parameters were within normal standard values according to WHO 2010 criteria (semen volume ≥ 1.5 mL, sperm concentration ≥ 15x10 6 /mL, total motility ≥ 40%, progressive motility ≥ 32% and vitality ≥ 4%) and those below these values. Hormonal evaluation For hormonal assessment, peripheral blood samples were collected from all cases between 8:00 a.m. and 11:00 a.m. following a 10–12 hour overnight fasting. The serum levels of total testosterone (TT), prolactin, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were measured. Laboratory tests were repeated a few days later when any abnormal findings were encountered. Statistical analysis Statistical analysis was performed using STATA version 11 (StataCorp LP, College Station, TX). The normality of the distribution of the variables was analyzed using the Kolmogorov-Smirnov test. Student's t-test and Mann-Whitney U test were used for the comparison of normally distributed and non-normally distributed variables, respectively. Categorical variables were compared with the chi-square test. P < 0.05 was considered statistically significant. RESULTS A total of 1303 patients were included in the study. Of these patients, 316 (24.2%) were previously exposed to SARS-CoV-2 infection, and the remaining 987 (75.8%) patients were COVID-19 naive. The mean ages of the exposed and non-exposed patients were similar (31.2 ± 6.6 vs. 30.5 ± 6.4, p = 0.73). There was no statistically significant difference in hormone profile (FSH, LH, PRL, and total testosterone) and semen parameters between patients exposed to COVID-19 infection and non-exposed patients. Details are given in Table 1 . Table 1 Comparison of patients exposed to COVID-19 infection and COVID naive patients in terms of hormone profile and semen parameters Patients exposed to COVID-19 (n = 316) COVID-19 naive patients (n = 987) p value Age (year) 31.2 ± 6.6 30.5 ± 6.4 0.73 Hormone profile FSH (mIU/mL) 5.8 ± 5.5 6.9 ± 10.2 0.08 LH (mIU/mL) 6.3 ± 2.9 7.2 ± 5.6 0.67 Prolactin (ng/mL) 12.7 ± 8.1 12.7 ± 5.9 0.95 Total testosterone (ng/dL) 4.3 ± 2.1 4.1 ± 1.7 0.44 Semen parameters Semen volume (mL) 3.3 ± 1.6 3.2 ± 1.6 0.17 Sperm concentration (million/mL) 28.1 ± 25.9 27.9 ± 25.4 0.94 Progressive motility (%) 37.9 ± 19.2 38.9 ± 19.4 0.39 Total motility (%) 44.4 ± 20.9 45.9 ± 21.1 0.27 Total motile sperm count (million) 41.3 ± 37.3 40.4 ± 38.2 0.78 Morphology 3.7 ± 2.6 3.6 ± 2.4 0.63 Data are expressed as mean ± standard deviation. Semen parameters of 568 (43.6%) patients were within normal standard values according to WHO 2010 criteria. In 735 (56.4%) patients, any of the semen parameters were below the reference values. There was no significant difference in exposure to SARS-CoV-2 infection between patients with normal and abnormal semen analysis parameters ( p = 0.62) (Table 2 ). Table 2 Distribution of patients with normal and abnormal semen analysis parameters according to whether they were exposed to COVID-19 infection or not Patients with normal semen parameters Patients with abnormal semen parameters P value 0.62 Patients exposed to COVID-19 134 (42.4%) 182 (57.6%) COVID-19 naive patients 434 (44%) 553 (56%) Data are presented as number and percentage of patients. DISCUSSION To our knowledge, this retrospective case-control study is the first to investigate the relationship between semen quality and susceptibility to SARS-CoV-2 infection. The results of the study showed that there was no significant difference between the pre-disease semen parameters of patients exposed to SARS-CoV-2 infection and the semen parameters of SARS-CoV-2 naive individuals. Additionally, there was no significant difference in exposure to SARS-CoV-2 infection between patients with normal and abnormal semen analysis parameters according to WHO 2010 criteria. Moreover, serum FSH, LH, PRL and total testosterone levels were comparable between patients exposed to SARS-CoV-2 infection and naive individuals, There is growing evidence that male fertility and sperm quality are closely related to overall health. Various studies have shown that the severity of comorbidity is inversely correlated with semen quality ( 6 , 15 ). In a cross-sectional study involving 9,387 patients, men with a higher Charlson comorbidity index scores had lower semen volume, sperm concentration, motility, total sperm count, and morphology scores ( 6 ). The deficiency of some common regulatory genes effective on both spermatogenesis and cell division has been held responsible for the coexistence of infertility and comorbidities ( 24 – 26 ). Additionally, it has been suggested that hormonal, environmental and intrauterine factors may also explain the link ( 27 , 28 ). Taking these data together, we hypothesized that patients with poorer semen quality may be more susceptible to SARS-CoV-2 infection, since semen quality and comorbidities are closely related and comorbidities increase individuals' susceptibility to SARS-CoV-2. However, based on our findings, there does not seem to be any relationship between sperm quality and susceptibility to SARS-CoV-2 infection. Despite existing evidence for the immunosuppressive effects of testosterone against bacterial and viral infections, the results of the present study revealed no significant relationship between susceptibility to SARS-CoV-2 infection and serum total testosterone level. Serum total testosterone levels of patients exposed to SARS-CoV-2 infection and naïve individuals were comparable ( 29 ). In various studies, the susceptibility to SARS-CoV-2 infection in patients receiving androgen deprivation therapy (ADT) for prostate cancer has been investigated and conflicting results have been reported ( 30 , 31 ). Montopoli et al. reported that SARS-CoV-2 infection rates were lower in patients receiving ADT compared to those not receiving ADT [odds ratio (OR) 4.05, 95% confidence interval (CI) 1.55–10.59, p = 0.00043] ( 30 ). In contrast, more recently Klein et al. did not observe a protective effect of ADT from SARS-CoV-2 (OR 0.93, 95% CI 0.54–1.61, p = 0.8) ( 31 ). Further studies are needed to confirm the effect of testosterone on susceptibility to SARS-CoV-2 infection. PRL, a lactogenic hormone, is also known to play an important role in regulating immune function during viral infections ( 23 ). Sen et al. suggested that low serum PRL levels increase susceptibility to SARS-CoV-2 infection, while high PRL levels are protective against SARS-CoV-2 infection ( 32 ). Moreover, they hypothesized that controlled enhancement of serum PRL levels through dopamine antagonists may provide an advantage in avoiding COVID-19 by stimulating both acquired and innate immunity. However, these hypotheses were not confirmed in this study, and our results revealed that there was no significant difference in serum PRL levels between patients exposed to SARS-CoV-2 infection and naive individuals. This retrospective study has several limitations. First, all patients were collected from a single center. Further studies involving various centers and populations will be necessary to confirm our findings. Second, data were not available regarding comorbidities of the patients included in the study that might affect their susceptibility to SARS-CoV-2 infection. Finally, some patients whose semen parameters were below standard values according to WHO criteria did not have a second confirmatory semen sample. CONCLUSIONS This study demonstrated that baseline semen quality and serum reproductive hormone levels (total testosterone, PRL, FSH, and LH) are not indicators of susceptibility to SARS-CoV-2 infection. Abbreviations FSH follicle-stimulating hormone LH luteinizing hormone. Declarations Availability of Data and Materials: The data of the study are not publicly available. Author Contributions: Research conception and design: Y.P, H.K, H.B, and M.K. Data acquisition: Y.P, H.K, H.G, T.B.B, H.B, and M.K. Statistical analysis: Y.P, H.K, and M.K Data analysis and interpretation: Y.P, H.K, H.G, T.B.B, H.B, and M.K. Drafting of the manuscript: Y.P, H.K, H.G, T.B.B, H.B, and M.K. Critical revision of the manuscript: Y.P, H.K, H.B, and M.K. Supervision: Y.P, H.K, H.B, and M.K. Approval of the final manuscript: Y.P, H.K, H.G, T.B.B, H.B, and M.K. Ethical Statement: All procedures performed in this study involving human participants were in accordance with the Declaration of Helsinki (as revised in 2013). The present study protocol was reviewed and approved by the institutional review board of the Istanbul Training and Research Hospital (No.: 2019-607). Acknowledgments: None Funding: This research received no external funding. Conflict of Interest: The authors have no conflicts of interest to declare. Consent for publication: Not applicable References Coronaviridae Study Group of the International Committee on Taxonomy of V. The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. Nat Microbiol. 2020;5(4):536-44. World Health Organization. WHO Coronavirus Disease (COVID-19) Dashboard. Available online: https://covid19.who.int/table (accessed on 09 September 2023). Li B, Yang J, Zhao F, Zhi L, Wang X, Liu L, et al. 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Fagone P, Ciurleo R, Lombardo SD, Iacobello C, Palermo CI, Shoenfeld Y, et al. Transcriptional landscape of SARS-CoV-2 infection dismantles pathogenic pathways activated by the virus, proposes unique sex-specific differences and predicts tailored therapeutic strategies. Autoimmun Rev. 2020;19(7):102571. Pereira Suarez AL, Lopez-Rincon G, Martinez Neri PA, Estrada-Chavez C. Prolactin in inflammatory response. Adv Exp Med Biol. 2015;846:243-64. Cejkova P, Chroma V, Cerna M, Markova M, Marek J, Lacinova Z, et al. Monitoring of the course of sepsis in hematooncological patients by extrapituitary prolactin expression in peripheral blood monocytes. Physiol Res. 2012;61(5):481-8. Zaid D, Greenman Y. Human Immunodeficiency Virus Infection and the Endocrine System. Endocrinol Metab (Seoul). 2019;34(2):95-105. Raman JD, Nobert CF, Goldstein M. Increased incidence of testicular cancer in men presenting with infertility and abnormal semen analysis. J Urol. 2005;174(5):1819-22; discussion 22. Walsh TJ, Schembri M, Turek PJ, Chan JM, Carroll PR, Smith JF, et al. Increased risk of high-grade prostate cancer among infertile men. Cancer. 2010;116(9):2140-7. Eisenberg ML, Betts P, Herder D, Lamb DJ, Lipshultz LI. Increased risk of cancer among azoospermic men. Fertil Steril. 2013;100(3):681-5. Matzuk MM, Lamb DJ. The biology of infertility: research advances and clinical challenges. Nat Med. 2008;14(11):1197-213. Skakkebaek NE, Rajpert-De Meyts E, Main KM. Testicular dysgenesis syndrome: an increasingly common developmental disorder with environmental aspects. Hum Reprod. 2001;16(5):972-8. Salciccia S, Del Giudice F, Eisenberg ML, Mastroianni CM, De Berardinis E, Ricciuti GP, et al. Testosterone target therapy: focus on immune response, controversies and clinical implications in patients with COVID-19 infection. Ther Adv Endocrinol Metab. 2021;12:20420188211010105. Montopoli M, Zumerle S, Vettor R, Rugge M, Zorzi M, Catapano CV, et al. 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):1040-5. Klein EA, Li J, Milinovich A, Schold JD, Sharifi N, Kattan MW, et al. Androgen Deprivation Therapy in Men with Prostate Cancer Does Not Affect Risk of Infection with SARS-CoV-2. J Urol. 2021;205(2):441-3. Sen A. Repurposing prolactin as a promising immunomodulator for the treatment of COVID-19: Are common Antiemetics the wonder drug to fight coronavirus? Med Hypotheses. 2020;144:110208. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3964500","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":279663338,"identity":"a1ab47ec-0ad9-49d1-8562-0e02da29845b","order_by":0,"name":"Yasar PAZIR","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAxUlEQVRIiWNgGAWjYLCCBAabBAijgHgtaQkMbCCGAfH2HIZoYSBGi8Ht5scfHu45n8cv35344YEBgzy/2AECWu4cMzBIeHa7WLKNd7ME0GGGM2cnENByI8EgIeHA7cQNx3g3gLQkGNwmqCX9w4GEA+dAWjb/IFJLjmFDwoEDIC3biLNF8s6ZYoaEA8mJM9tyt1kkGEgQ9gvf7fbNH38csEvsZz67+eaPCht5fmkCWhRuoPIl8CsHAfkZhNWMglEwCkbBSAcAjjVKQV1TPL8AAAAASUVORK5CYII=","orcid":"https://orcid.org/0000-0002-0056-7459","institution":"Haseki Training and Research Hospital: Istanbul Haseki Egitim Ve Arastirma Hastanesi","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Yasar","middleName":"","lastName":"PAZIR","suffix":""},{"id":279663340,"identity":"1f0aa3c2-5b31-49b6-9229-f1d57e2352a3","order_by":1,"name":"Huseyin Kocan","email":"","orcid":"","institution":"Istanbul Kanuni Sultan Suleyman Egitim ve Arastirma Hastanesi","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Huseyin","middleName":"","lastName":"Kocan","suffix":""},{"id":279663341,"identity":"4ee5ec4a-6c48-4e1c-aa24-9f97e0d174aa","order_by":2,"name":"Haydar Guler","email":"","orcid":"","institution":"Istanbul Kanuni Sultan Suleyman Egitim ve Arastirma Hastanesi","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Haydar","middleName":"","lastName":"Guler","suffix":""},{"id":279663343,"identity":"c00e7334-ea74-4827-836e-05e0fd32fc27","order_by":3,"name":"Taha Burak Bulut","email":"","orcid":"","institution":"Istanbul Education Research Hospital: TC Saglik Bakanligi Istanbul Egitim Arastirma Hastanesi","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Taha","middleName":"Burak","lastName":"Bulut","suffix":""},{"id":279663345,"identity":"9afd73e0-7a72-4152-ac0b-4ede4feb2340","order_by":4,"name":"Huseyin Besiroglu","email":"","orcid":"","institution":"Istanbul University-Cerrahpasa Cerrahpasa Faculty of Medicine: Istanbul Universitesi-Cerrahpasa Cerrahpasa Tip Fakultesi","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Huseyin","middleName":"","lastName":"Besiroglu","suffix":""},{"id":279663347,"identity":"00f7632a-413a-4218-a457-42ffeef55e86","order_by":5,"name":"Mustafa Kadıhasanoglu","email":"","orcid":"","institution":"İstanbul Üniversitesi Cerrahpaşa Tıp Fakültesi: Istanbul Universitesi-Cerrahpasa Cerrahpasa Tip Fakultesi","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Mustafa","middleName":"","lastName":"Kadıhasanoglu","suffix":""}],"badges":[],"createdAt":"2024-02-17 15:42:24","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3964500/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3964500/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":58442494,"identity":"2447ed12-f9b4-421a-825f-39278c70ddf7","added_by":"auto","created_at":"2024-06-16 12:11:18","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":388860,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3964500/v1/6780f484-2356-433f-958e-fabafab1ea0f.pdf"}],"financialInterests":"","formattedTitle":"Relationship of semen quality and reproductive hormones with susceptibility to COVID-19 infection","fulltext":[{"header":"BACKGROUND","content":"\u003cp\u003eA novel beta-coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread rapidly worldwide and caused the coronavirus disease 2019 (COVID-19) pandemic (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). Since it was first identified in China in December 2019, more than 767,750,000 cases of COVID-19 have been reported worldwide as of June 2023 (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Clinical studies have demonstrated that comorbidities such as hypertension, diabetes, dyslipidemia, and obesity weaken the immune system through various mechanisms, increase the susceptibility of individuals to COVID-19, and worsen the prognosis of the disease (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThere is increasing evidence that semen quality reflects the overall health status of individuals and is a marker of future health (\u003cspan additionalcitationids=\"CR6 CR7\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). Various studies have indicated that infertile men have a higher rate of comorbidities than fertile men (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). In addition, poor semen parameters and male infertility have been shown to be an early indicator of an increased risk of cardiovascular disease, diabetes, hyperlipidemia, cancer, and even overall mortality (\u003cspan additionalcitationids=\"CR10 CR11 CR12 CR13\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). Although the link between male reproductive health and somatic health has not been fully elucidated, it is suggested that genetic, hormonal, environmental and epigenetic factors play a role in this relationship (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). Moreover, comorbidities may directly impair male reproductive function (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). Therefore, it has been hypothesized that semen analysis may serve as a potential biomarker for overall health counseling, such as potential preventive health measures and chronic disease management, beyond fertility counseling.\u003c/p\u003e \u003cp\u003eSARS-CoV-2 infects the host via angiotensin converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) expressed in different tissues such as lung, heart, testis, prostate and kidney (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). The transcription of the TMPRSS2 and ACE2 genes is regulated by the androgen receptor (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). It has been shown that suppression of androgen hormones causes a decrease in ACE2 expression and activity (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). In addtion, reproductive hormones have significant regulatory effects on the immune system and the function of inflammatory cells (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). Testosterone increases the susceptibility to both viral and bacterial infections by suppressing the adaptive and innate immune system (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). In contrast, prolactin (PRL) plays a key role in stimulating both innate and adaptive immunity (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). It has been reported that hypoprolactinemia may even cause death due to opportunistic infections (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). These findings suggest that the hormonal status of individuals might play an important role in susceptibility to COVID-19 and severity of clinical course.\u003c/p\u003e \u003cp\u003eIn the present study, it was aimed to investigate whether baseline semen quality and serum reproductive hormone levels are potential indicators of susceptibility to SARS-CoV-2 infection.\u003c/p\u003e"},{"header":"PATIENTS AND METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design and population\u003c/h2\u003e \u003cp\u003eThe medical records of patients who underwent semen analysis and hormonal evaluation due to couple's infertility or other medical reasons in a tertiary center between January 2020 and January 2022 were retrospectively analyzed. Men between the ages of 18\u0026ndash;49 were included in the study. Before semen analysis and hormonal evaluation, patients who (i) had a history of COVID-19 disease and (ii) were previously exposed to treatments that could affect the basal parameters of patients such as gonadotropins, antioxidants, anti-estrogens and testosterone replacement were excluded from the study.\u003c/p\u003e \u003cp\u003eA total of 1303 patients met the study criteria. Among these patients, those previously exposed to SARS-CoV-2 infection were identified through reverse transcription-polymerase chain reaction (RT-PCR) test of pharyngeal and nasal swab samples and/or the detection of typical COVID-19 pneumonia (ground glass opacities and consolidation areas especially in the peripheral and lower lobes) on chest imaging in their medical records.\u003c/p\u003e \u003cp\u003e All procedures performed in this study involving human participants were in accordance with the Declaration of Helsinki (as revised in 2013). The present study protocol was reviewed and approved by the institutional review board.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eSemen analysis\u003c/h2\u003e \u003cp\u003eSemen samples were collected by masturbation after three days of abstinence and analyzed within the first hour after ejaculation by the experienced andrology laboratory staff. Semen volume, sperm concentration, motility and morphology of each case were determined in accordance with the recommendations of the WHO 2010 laboratory manual for the examination and processing of human semen (5th edition). The patients were categorized as those whose semen parameters were within normal standard values according to WHO 2010 criteria (semen volume\u0026thinsp;\u0026ge;\u0026thinsp;1.5 mL, sperm concentration\u0026thinsp;\u0026ge;\u0026thinsp;15x10\u003csup\u003e6\u003c/sup\u003e/mL, total motility\u0026thinsp;\u0026ge;\u0026thinsp;40%, progressive motility\u0026thinsp;\u0026ge;\u0026thinsp;32% and vitality\u0026thinsp;\u0026ge;\u0026thinsp;4%) and those below these values.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eHormonal evaluation\u003c/h2\u003e \u003cp\u003eFor hormonal assessment, peripheral blood samples were collected from all cases between 8:00 a.m. and 11:00 a.m. following a 10\u0026ndash;12 hour overnight fasting. The serum levels of total testosterone (TT), prolactin, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were measured. Laboratory tests were repeated a few days later when any abnormal findings were encountered.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eStatistical analysis was performed using STATA version 11 (StataCorp LP, College Station, TX). The normality of the distribution of the variables was analyzed using the Kolmogorov-Smirnov test. Student's t-test and Mann-Whitney U test were used for the comparison of normally distributed and non-normally distributed variables, respectively. Categorical variables were compared with the chi-square test. \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"RESULTS","content":"\u003cp\u003eA total of 1303 patients were included in the study. Of these patients, 316 (24.2%) were previously exposed to SARS-CoV-2 infection, and the remaining 987 (75.8%) patients were COVID-19 naive. The mean ages of the exposed and non-exposed patients were similar (31.2\u0026thinsp;\u0026plusmn;\u0026thinsp;6.6 vs. 30.5\u0026thinsp;\u0026plusmn;\u0026thinsp;6.4, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.73). There was no statistically significant difference in hormone profile (FSH, LH, PRL, and total testosterone) and semen parameters between patients exposed to COVID-19 infection and non-exposed patients. Details are given in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of patients exposed to COVID-19 infection and COVID naive patients in terms of hormone profile and semen parameters\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePatients exposed to COVID-19 (n\u0026thinsp;=\u0026thinsp;316)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCOVID-19 naive patients (n\u0026thinsp;=\u0026thinsp;987)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (year)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e31.2\u0026thinsp;\u0026plusmn;\u0026thinsp;6.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e30.5\u0026thinsp;\u0026plusmn;\u0026thinsp;6.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.73\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHormone profile\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFSH \u003cem\u003e(mIU/mL)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e5.8\u0026thinsp;\u0026plusmn;\u0026thinsp;5.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e6.9\u0026thinsp;\u0026plusmn;\u0026thinsp;10.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.08\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLH \u003cem\u003e(mIU/mL)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e6.3\u0026thinsp;\u0026plusmn;\u0026thinsp;2.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e7.2\u0026thinsp;\u0026plusmn;\u0026thinsp;5.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.67\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProlactin \u003cem\u003e(ng/mL)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e12.7\u0026thinsp;\u0026plusmn;\u0026thinsp;8.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e12.7\u0026thinsp;\u0026plusmn;\u0026thinsp;5.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.95\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal testosterone \u003cem\u003e(ng/dL)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e4.3\u0026thinsp;\u0026plusmn;\u0026thinsp;2.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e4.1\u0026thinsp;\u0026plusmn;\u0026thinsp;1.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.44\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSemen parameters\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSemen volume (mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e3.3\u0026thinsp;\u0026plusmn;\u0026thinsp;1.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e3.2\u0026thinsp;\u0026plusmn;\u0026thinsp;1.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.17\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSperm concentration (million/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e28.1\u0026thinsp;\u0026plusmn;\u0026thinsp;25.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e27.9\u0026thinsp;\u0026plusmn;\u0026thinsp;25.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.94\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProgressive motility (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e37.9\u0026thinsp;\u0026plusmn;\u0026thinsp;19.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e38.9\u0026thinsp;\u0026plusmn;\u0026thinsp;19.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.39\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal motility (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e44.4\u0026thinsp;\u0026plusmn;\u0026thinsp;20.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e45.9\u0026thinsp;\u0026plusmn;\u0026thinsp;21.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.27\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal motile sperm count (million)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e41.3\u0026thinsp;\u0026plusmn;\u0026thinsp;37.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e40.4\u0026thinsp;\u0026plusmn;\u0026thinsp;38.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.78\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMorphology\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e3.7\u0026thinsp;\u0026plusmn;\u0026thinsp;2.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e3.6\u0026thinsp;\u0026plusmn;\u0026thinsp;2.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.63\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eData are expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eSemen parameters of 568 (43.6%) patients were within normal standard values according to WHO 2010 criteria. In 735 (56.4%) patients, any of the semen parameters were below the reference values. There was no significant difference in exposure to SARS-CoV-2 infection between patients with normal and abnormal semen analysis parameters (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.62) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDistribution of patients with normal and abnormal semen analysis parameters according to whether they were exposed to COVID-19 infection or not\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePatients with normal semen parameters\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePatients with abnormal semen parameters\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.62\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePatients exposed to COVID-19\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e134 (42.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e182 (57.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCOVID-19 naive patients\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e434 (44%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e553 (56%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eData are presented as number and percentage of patients.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eTo our knowledge, this retrospective case-control study is the first to investigate the relationship between semen quality and susceptibility to SARS-CoV-2 infection. The results of the study showed that there was no significant difference between the pre-disease semen parameters of patients exposed to SARS-CoV-2 infection and the semen parameters of SARS-CoV-2 naive individuals. Additionally, there was no significant difference in exposure to SARS-CoV-2 infection between patients with normal and abnormal semen analysis parameters according to WHO 2010 criteria. Moreover, serum FSH, LH, PRL and total testosterone levels were comparable between patients exposed to SARS-CoV-2 infection and naive individuals,\u003c/p\u003e \u003cp\u003eThere is growing evidence that male fertility and sperm quality are closely related to overall health. Various studies have shown that the severity of comorbidity is inversely correlated with semen quality (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). In a cross-sectional study involving 9,387 patients, men with a higher Charlson comorbidity index scores had lower semen volume, sperm concentration, motility, total sperm count, and morphology scores (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). The deficiency of some common regulatory genes effective on both spermatogenesis and cell division has been held responsible for the coexistence of infertility and comorbidities (\u003cspan additionalcitationids=\"CR25\" citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e). Additionally, it has been suggested that hormonal, environmental and intrauterine factors may also explain the link (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e). Taking these data together, we hypothesized that patients with poorer semen quality may be more susceptible to SARS-CoV-2 infection, since semen quality and comorbidities are closely related and comorbidities increase individuals' susceptibility to SARS-CoV-2. However, based on our findings, there does not seem to be any relationship between sperm quality and susceptibility to SARS-CoV-2 infection.\u003c/p\u003e \u003cp\u003eDespite existing evidence for the immunosuppressive effects of testosterone against bacterial and viral infections, the results of the present study revealed no significant relationship between susceptibility to SARS-CoV-2 infection and serum total testosterone level. Serum total testosterone levels of patients exposed to SARS-CoV-2 infection and na\u0026iuml;ve individuals were comparable (\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e). In various studies, the susceptibility to SARS-CoV-2 infection in patients receiving androgen deprivation therapy (ADT) for prostate cancer has been investigated and conflicting results have been reported (\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e). Montopoli et al. reported that SARS-CoV-2 infection rates were lower in patients receiving ADT compared to those not receiving ADT [odds ratio (OR) 4.05, 95% confidence interval (CI) 1.55\u0026ndash;10.59, p\u0026thinsp;=\u0026thinsp;0.00043] (\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e). In contrast, more recently Klein et al. did not observe a protective effect of ADT from SARS-CoV-2 (OR 0.93, 95% CI 0.54\u0026ndash;1.61, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.8) (\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e). Further studies are needed to confirm the effect of testosterone on susceptibility to SARS-CoV-2 infection.\u003c/p\u003e \u003cp\u003ePRL, a lactogenic hormone, is also known to play an important role in regulating immune function during viral infections (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). Sen et al. suggested that low serum PRL levels increase susceptibility to SARS-CoV-2 infection, while high PRL levels are protective against SARS-CoV-2 infection (\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e). Moreover, they hypothesized that controlled enhancement of serum PRL levels through dopamine antagonists may provide an advantage in avoiding COVID-19 by stimulating both acquired and innate immunity. However, these hypotheses were not confirmed in this study, and our results revealed that there was no significant difference in serum PRL levels between patients exposed to SARS-CoV-2 infection and naive individuals.\u003c/p\u003e \u003cp\u003eThis retrospective study has several limitations. First, all patients were collected from a single center. Further studies involving various centers and populations will be necessary to confirm our findings. Second, data were not available regarding comorbidities of the patients included in the study that might affect their susceptibility to SARS-CoV-2 infection. Finally, some patients whose semen parameters were below standard values according to WHO criteria did not have a second confirmatory semen sample.\u003c/p\u003e"},{"header":"CONCLUSIONS","content":"\u003cp\u003eThis study demonstrated that baseline semen quality and serum reproductive hormone levels (total testosterone, PRL, FSH, and LH) are not indicators of susceptibility to SARS-CoV-2 infection.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eFSH\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003efollicle-stimulating hormone\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eLH\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eluteinizing hormone.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003eAvailability of Data and Materials:\u0026nbsp;The data of the study are not publicly available.\u003c/p\u003e\n\u003cp\u003eAuthor Contributions:\u0026nbsp;Research conception and design:\u0026nbsp;Y.P, H.K, H.B, and M.K. Data acquisition:\u0026nbsp;Y.P, H.K, H.G, T.B.B, H.B, and M.K. Statistical analysis:\u0026nbsp;Y.P, H.K, and M.K\u0026nbsp;Data analysis and interpretation:\u0026nbsp;Y.P, H.K, H.G, T.B.B, H.B, and M.K. Drafting of the manuscript:\u0026nbsp;Y.P, H.K, H.G, T.B.B, H.B, and M.K. Critical revision of the manuscript:\u0026nbsp;Y.P, H.K, H.B, and M.K. Supervision:\u0026nbsp;Y.P, H.K, H.B, and M.K. Approval of the final manuscript:\u0026nbsp;Y.P, H.K, H.G, T.B.B, H.B, and M.K.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical Statement:\u003c/strong\u003e All procedures performed in this study involving human participants were in accordance with the Declaration of Helsinki (as revised in 2013).\u003cem\u003e\u0026nbsp;The present study protocol was\u003c/em\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003ereviewed and\u003cem\u003e\u0026nbsp;approved by the institutional review board of the Istanbul Training and Research Hospital\u0026nbsp;\u003c/em\u003e(No.: 2019-607).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments:\u0026nbsp;\u003c/strong\u003eNone\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u003c/strong\u003e This research received no external funding.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of Interest:\u0026nbsp;\u003c/strong\u003eThe authors have no conflicts of interest to declare.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication:\u0026nbsp;\u003c/strong\u003eNot applicable\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eCoronaviridae Study Group of the International Committee on Taxonomy of V. The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. Nat Microbiol. 2020;5(4):536-44.\u003c/li\u003e\n\u003cli\u003eWorld Health Organization. WHO Coronavirus Disease (COVID-19) Dashboard. Available online: https://covid19.who.int/table (accessed on 09 September 2023). \u003c/li\u003e\n\u003cli\u003eLi B, Yang J, Zhao F, Zhi L, Wang X, Liu L, et al. Prevalence and impact of cardiovascular metabolic diseases on COVID-19 in China. Clin Res Cardiol. 2020;109(5):531-8.\u003c/li\u003e\n\u003cli\u003eWang D, Yin Y, Hu C, Liu X, Zhang X, Zhou S, et al. Clinical course and outcome of 107 patients infected with the novel coronavirus, SARS-CoV-2, discharged from two hospitals in Wuhan, China. Crit Care. 2020;24(1):188.\u003c/li\u003e\n\u003cli\u003eJensen TK, Jacobsen R, Christensen K, Nielsen NC, Bostofte E. Good semen quality and life expectancy: a cohort study of 43,277 men. Am J Epidemiol. 2009;170(5):559-65.\u003c/li\u003e\n\u003cli\u003eEisenberg ML, Li S, Behr B, Pera RR, Cullen MR. Relationship between semen production and medical comorbidity. Fertil Steril. 2015;103(1):66-71.\u003c/li\u003e\n\u003cli\u003ePisarska MD. Fertility Status and Overall Health. Semin Reprod Med. 2017;35(3):203-4.\u003c/li\u003e\n\u003cli\u003eChoy JT, Eisenberg ML. Male infertility as a window to health. Fertil Steril. 2018;110(5):810-4.\u003c/li\u003e\n\u003cli\u003eSalonia A, Matloob R, Gallina A, Abdollah F, Sacca A, Briganti A, et al. Are infertile men less healthy than fertile men? Results of a prospective case-control survey. Eur Urol. 2009;56(6):1025-31.\u003c/li\u003e\n\u003cli\u003eKasman AM, Del Giudice F, Eisenberg ML. New insights to guide patient care: the bidirectional relationship between male infertility and male health. Fertil Steril. 2020;113(3):469-77.\u003c/li\u003e\n\u003cli\u003eEisenberg ML, Li S, Cullen MR, Baker LC. Increased risk of incident chronic medical conditions in infertile men: analysis of United States claims data. Fertil Steril. 2016;105(3):629-36.\u003c/li\u003e\n\u003cli\u003eCazzaniga W, Capogrosso P, Ventimiglia E, Pederzoli F, Boeri L, Frego N, et al. High Blood Pressure Is a Highly Prevalent but Unrecognised Condition in Primary Infertile Men: Results of a Cross-sectional Study. Eur Urol Focus. 2020;6(1):178-83.\u003c/li\u003e\n\u003cli\u003eEisenberg ML, Li S, Brooks JD, Cullen MR, Baker LC. Increased risk of cancer in infertile men: analysis of U.S. claims data. J Urol. 2015;193(5):1596-601.\u003c/li\u003e\n\u003cli\u003eHanson BM, Eisenberg ML, Hotaling JM. Male infertility: a biomarker of individual and familial cancer risk. Fertil Steril. 2018;109(1):6-19.\u003c/li\u003e\n\u003cli\u003eVentimiglia E, Capogrosso P, Boeri L, Serino A, Colicchia M, Ippolito S, et al. Infertility as a proxy of general male health: results of a cross-sectional survey. Fertil Steril. 2015;104(1):48-55.\u003c/li\u003e\n\u003cli\u003eZiegler CGK, Allon SJ, Nyquist SK, Mbano IM, Miao VN, Tzouanas CN, et al. SARS-CoV-2 Receptor ACE2 Is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and Is Detected in Specific Cell Subsets across Tissues. Cell. 2020;181(5):1016-35 e19.\u003c/li\u003e\n\u003cli\u003eBarnes BJ, Adrover JM, Baxter-Stoltzfus A, Borczuk A, Cools-Lartigue J, Crawford JM, et al. Targeting potential drivers of COVID-19: Neutrophil extracellular traps. J Exp Med. 2020;217(6).\u003c/li\u003e\n\u003cli\u003eDalpiaz PL, Lamas AZ, Caliman IF, Ribeiro RF, Jr., Abreu GR, Moyses MR, et al. Sex Hormones Promote Opposite Effects on ACE and ACE2 Activity, Hypertrophy and Cardiac Contractility in Spontaneously Hypertensive Rats. PLoS One. 2015;10(5):e0127515.\u003c/li\u003e\n\u003cli\u003eTaneja V. Sex Hormones Determine Immune Response. Front Immunol. 2018;9:1931.\u003c/li\u003e\n\u003cli\u003eFagone P, Ciurleo R, Lombardo SD, Iacobello C, Palermo CI, Shoenfeld Y, et al. Transcriptional landscape of SARS-CoV-2 infection dismantles pathogenic pathways activated by the virus, proposes unique sex-specific differences and predicts tailored therapeutic strategies. Autoimmun Rev. 2020;19(7):102571.\u003c/li\u003e\n\u003cli\u003ePereira Suarez AL, Lopez-Rincon G, Martinez Neri PA, Estrada-Chavez C. Prolactin in inflammatory response. Adv Exp Med Biol. 2015;846:243-64.\u003c/li\u003e\n\u003cli\u003eCejkova P, Chroma V, Cerna M, Markova M, Marek J, Lacinova Z, et al. Monitoring of the course of sepsis in hematooncological patients by extrapituitary prolactin expression in peripheral blood monocytes. Physiol Res. 2012;61(5):481-8.\u003c/li\u003e\n\u003cli\u003eZaid D, Greenman Y. Human Immunodeficiency Virus Infection and the Endocrine System. Endocrinol Metab (Seoul). 2019;34(2):95-105.\u003c/li\u003e\n\u003cli\u003eRaman JD, Nobert CF, Goldstein M. Increased incidence of testicular cancer in men presenting with infertility and abnormal semen analysis. J Urol. 2005;174(5):1819-22; discussion 22.\u003c/li\u003e\n\u003cli\u003eWalsh TJ, Schembri M, Turek PJ, Chan JM, Carroll PR, Smith JF, et al. Increased risk of high-grade prostate cancer among infertile men. Cancer. 2010;116(9):2140-7.\u003c/li\u003e\n\u003cli\u003eEisenberg ML, Betts P, Herder D, Lamb DJ, Lipshultz LI. Increased risk of cancer among azoospermic men. Fertil Steril. 2013;100(3):681-5.\u003c/li\u003e\n\u003cli\u003eMatzuk MM, Lamb DJ. The biology of infertility: research advances and clinical challenges. Nat Med. 2008;14(11):1197-213.\u003c/li\u003e\n\u003cli\u003eSkakkebaek NE, Rajpert-De Meyts E, Main KM. Testicular dysgenesis syndrome: an increasingly common developmental disorder with environmental aspects. Hum Reprod. 2001;16(5):972-8.\u003c/li\u003e\n\u003cli\u003eSalciccia S, Del Giudice F, Eisenberg ML, Mastroianni CM, De Berardinis E, Ricciuti GP, et al. Testosterone target therapy: focus on immune response, controversies and clinical implications in patients with COVID-19 infection. Ther Adv Endocrinol Metab. 2021;12:20420188211010105.\u003c/li\u003e\n\u003cli\u003eMontopoli M, Zumerle S, Vettor R, Rugge M, Zorzi M, Catapano CV, et al. 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):1040-5.\u003c/li\u003e\n\u003cli\u003eKlein EA, Li J, Milinovich A, Schold JD, Sharifi N, Kattan MW, et al. Androgen Deprivation Therapy in Men with Prostate Cancer Does Not Affect Risk of Infection with SARS-CoV-2. J Urol. 2021;205(2):441-3.\u003c/li\u003e\n\u003cli\u003eSen A. Repurposing prolactin as a promising immunomodulator for the treatment of COVID-19: Are common Antiemetics the wonder drug to fight coronavirus? Med Hypotheses. 2020;144:110208.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"semen quality, hormone, susceptibility, SARS-CoV-2, COVID-19","lastPublishedDoi":"10.21203/rs.3.rs-3964500/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3964500/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground and Aim:\u003c/strong\u003e There is increasing evidence that semen quality reflects the overall health status of individuals and is a marker of future health. In addition, reproductive hormones have significant regulatory effects on the immune system and the function of inflammatory cells.\u003cstrong\u003e \u003c/strong\u003eIn this study, it was aimed to investigate whether baseline semen quality and serum reproductive hormone levels are potential indicators of susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) \u0026nbsp;infection.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e The medical records of a total of 1303 patients who underwent semen analysis and hormonal evaluation including total testosterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin (PRL for infertility or other medical reasons were retrospectively analyzed. Among these patients, 316 were determined to have previously been exposed to SARS-CoV-2 infection.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003eThere was no statistically significant difference in baseline hormone profile (FSH, LH, PRL, and total testosterone) and semen parameters between patients exposed to SARS-CoV-2 infection and non-exposed patients.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e: This study demonstrated that baseline semen quality and serum reproductive hormone levels (total testosterone, PRL, FSH, and LH) are not indicators of susceptibility to SARS-CoV-2 infection.\u003c/p\u003e","manuscriptTitle":"Relationship of semen quality and reproductive hormones with susceptibility to COVID-19 infection","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-03-18 16:57:01","doi":"10.21203/rs.3.rs-3964500/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"63b8183b-cc4e-4e17-a95c-b507382180f5","owner":[],"postedDate":"March 18th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-06-16T12:03:12+00:00","versionOfRecord":[],"versionCreatedAt":"2024-03-18 16:57:01","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3964500","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3964500","identity":"rs-3964500","version":["v1"]},"buildId":"7rjqhiLT3MXkJMwkYKINL","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}