Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2024 Jul;85(1):44-66.
doi: 10.1007/s12020-024-03705-7. Epub 2024 Feb 12.

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

Rossella Cannarella  1   2 , Marta Marino  3 , Andrea Crafa  3 , Vincenzo Bagnara  4 , Sandro La Vignera  3 , Rosita A Condorelli  3 , Aldo E Calogero  3
Affiliations
Review

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

Rossella Cannarella et al. Endocrine. 2024 Jul.

Abstract

Introduction: Studies investigating the effects of SARS-CoV-2 on male reproductive function are few and heterogeneous, and results are often conflicting. This systematic review and meta-analysis was carried out on studies conducted in men with active or anamnestic SARS-CoV-2 infection to evaluate its consequences on the male sex hormone profile and semen parameters.

Materials and method: This meta-analysis follows the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) protocols. PubMed, Scopus, Cochrane, and Embase databases were searched to identify relevant studies. We originally selected 3553 articles. After the eligibility phase, 16 articles met our inclusion criteria encompassing 11 case-control studies and 5 cohort studies (2 prospective and 3 retrospective studies). We performed the quantitative analysis with Comprehensive Meta-Analysis Software. Cochran-Q and heterogeneity (I2) indexes were used to assess statistical heterogeneity. Sensitivity analysis and publication bias tests were also performed.

Results: Overall, 1250 patients with active or recent (up to 80 days before) COVID-19 infection and 1232 matched healthy controls were included. Sperm concentration, total sperm count, and total motility were significantly lower in patients compared with controls. Patients also showed lower levels of total testosterone and follicle-stimulating hormone, and higher levels of luteinizing hormone, 17β-estradiol, and prolactin compared with healthy controls. None of the included studies found the presence of SARS-CoV-2 mRNA in the semen of infected patients.

Conclusion: The present systematic review and meta-analysis suggests the presence of an association between SARS-CoV-2 infection and primary testicular damage manifested with a picture of altered steroidogenesis and worsening spermatogenesis. The absence of the virus in the seminal fluid indicates a low possibility of sexual transmission of the infection to partners and offspring. However, our findings mostly show short-term follow-up, while few studies have considered the long-term consequences of the viral infection, thus further studies are needed to evaluate the long-term consequences on male reproductive health.

Keywords: COVID-19; Infertility; SARS-CoV2; Testicular function; Testosterone.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
PRISMA flow diagram of literature screening
Fig. 2
Fig. 2
Forest plot of the luteinizing hormone in patients and controls
Fig. 3
Fig. 3
Forest plot of the follicle-stimulating hormone in patients and controls
Fig. 4
Fig. 4
Forest plot of total testosterone in patients and controls
Fig. 5
Fig. 5
Forest plot of prolactin in patients and controls
Fig. 6
Fig. 6
Forest plot of 17β-estradiol in patients and controls
Fig. 7
Fig. 7
Forest plot of sex hormone-binding globulin in patients and controls
Fig. 8
Fig. 8
Forest plot of sperm concentration in patients and controls
Fig. 9
Fig. 9
Forest plot of total sperm count in patients and controls
Fig. 10
Fig. 10
Forest plot of progressive sperm motility in patients and controls
Fig. 11
Fig. 11
Forest plot of total sperm motility in patients and controls
Fig. 12
Fig. 12
Mechanisms by which SARS-CoV-2 might damage testicular function in the acute phase and after short-term follow-up. In the acute phase, mechanisms mediated by inflammation, such as the increase in pro-inflammatory cytokines, lead to a reduction of GnRH pulses and, consequently, of serum LH and FSH levels. This is also favored by the use of glucocorticoids to treat COVID-19. After recovery, the hypothalamic-pituitary axis function will be restored. SARS-CoV-2 is also able to directly infect the testis and damage Leydig and Sertoli cells, thus leading to decreased testosterone biosynthesis and impaired spermatogenesis associated with elevated LH and unchanged FSH levels, in the short-term follow-up. The ability of these cells to regain their function will allow recovery from primary hypogonadism in the long-term follow-up. FSH follicle-stimulating hormone, GnRH gonadotropin-releasing hormone, IL interleukin, LH luteinizing hormone, SARS-CoV-2 severe acute respiratory syndrome Coronavirus 2, TNFα tumor necrosis factor α
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Wu F, Zhao S, Yu B, Chen YM, Wang W, Song ZG, et al. A new coronavirus associated with human respiratory disease in China. Nature. 2020;579(7798):265–269. doi: 10.1038/s41586-020-2008-3. - DOI - PMC - PubMed
    1. Chen L, Li Q, Zheng D, Jiang H, Wei Y, Zou L, et al. Correspondence: clinical characteristics of Covid-19 in Wuhan China. N. Engl. J. Med. 2020;100:1. - PMC - PubMed
    1. La Vignera S, Cannarella R, Condorelli RA, Torre F, Aversa A, Calogero AE. Sex-specific SARS-CoV2 mortality: among hormone-modulated ace2 expression, risk of venous thromboembolism and hypovitaminosis D. Int. J. Mol. Sci. 2020;21(8):5–10. doi: 10.3390/ijms21082948. - DOI - PMC - PubMed
    1. Marinelli L, Beccuti G, Zavattaro M, Cagnina S, Gesmundo I, Bona C, et al. Testosterone as a biomarker of adverse clinical outcomes in SARS-CoV-2 pneumonia. Biomedicines. 2022;10(4):1–11. doi: 10.3390/biomedicines10040820. - DOI - PMC - PubMed
    1. A. Alamo, C. De Luca, L.M. Mongioì, F. Barbagallo, R. Cannarella, S. La Vignera, A.E. Calogero, R.A. Condorelli, Mitochondrial Membrane Potential Predicts 4-Hour Sperm Motility. Biomedicines 8(7), 196 (2020). 10.3390/biomedicines8070196 - PMC - PubMed

LinkOut - more resources