The impact of acute SARS-CoV-2 on testicular function including insulin-like factor 3 [INSL3] in men with mild COVID-19: A longitudinal study

Mette Petri Lauritsen*, Thomas Leineweber Kristensen, Christine Bo Hansen, Uffe Vest Schneider, Anna Lando Talbot, Anne-Bine Skytte, Jørgen Holm Petersen, Trine Holm Johannsen, Anne Zedeler, Jakob Albrethsen, Anders Juul, Laerke Priskorn, Niels Jørgensen, Henrik Westh, Nina la Cour Freiesleben, Henriette Svarre Nielsen

*Corresponding author for this work
2 Citations (Scopus)


BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may affect the male reproductive system as it uses angiotensin-converting enzyme (ACE)2, which is expressed in testicular tissue, as an entry point into the cell. Few studies have evaluated the long-term effects of mild coronavirus disease 2019 (COVID-19) on testicular function, and insulin-like factor 3 (INSL3) levels have not previously been assessed during acute SARS-CoV-2 infection.

OBJECTIVES: The aim of the study was to assess the impact of acute SARS-CoV-2 infection on testicular function including INSL3 and the presence of SARS-CoV-2 RNA in semen in non-hospitalised men with mild COVID-19.

MATERIALS AND METHODS: This longitudinal study included 36 non-hospitalised SARS-CoV-2-positive men (median age 29 years). Inclusion was within seven days following a positive SARS-CoV-2 reverse-transcription polymerase chain reaction test. Reproductive hormone levels, semen parameters, and the presence of SARS-CoV-2 RNA in oropharyngeal and semen samples were assessed during acute SARS-CoV-2 infection (baseline) and at three- and six-month follow-up. Wilcoxon matched-pair signed-rank (two samples) test was used to assess time-related alterations in reproductive hormone levels and semen parameters.

RESULTS: Lower plasma testosterone (T) (total and calculated free (c-fT)) and higher luteinising hormone (LH) concentrations were observed during acute SARS-CoV-2 infection (baseline) compared to three- and six-month follow-up. Consequently, ratios of c-fT/LH were lower at baseline compared to three- and six-month follow-up (p < 0.001 and p = 0.003, respectively). Concomitantly, lower INSL3 concentrations were observed at baseline compared to three-month follow-up (p = 0.01). The total number of motile spermatozoa was also lower at baseline compared to six-month follow-up (p = 0.02). The alterations were detected irrespective of whether the men had experienced SARS-CoV-2-related fever episodes or not. No SARS-CoV-2 RNA was detected in semen at any time point.

DISCUSSION AND CONCLUSION: This study showed a reduction in testicular function, which was for the first time confirmed by INSL3, in men mildly affected by SARS-CoV-2 infection. The risk of transmission of SARS-CoV-2 RNA via semen seems to be low. Febrile episodes may impact testicular function, but a direct effect of SARS-CoV-2 cannot be excluded.

Original languageEnglish
Issue number2
Pages (from-to)437-446
Number of pages10
Publication statusPublished - Feb 2024


  • acute SARS-CoV-2
  • INSL3
  • insulin-like factor 3
  • male reproductive function
  • mild COVID-19
  • sexual transmission
  • testicular function
  • Semen
  • Humans
  • Male
  • Insulins
  • COVID-19
  • Luteinizing Hormone
  • Testosterone
  • SARS-CoV-2
  • RNA, Viral
  • Adult
  • Longitudinal Studies


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