Slide 1: Is Oral Testosterone a Potential Treatment for COVID-19 in Men?
Is Oral Testosterone a Potential Treatment for COVID - 19 in Men? Benjamin J. Bruno, PharmD/PhD 1 ; Kongnara Papangkorn, PhD 1 , Anthony DelConte, MD 1,2 , Nachiappan Chidambaram, PhD 1 , Kilyoung Kim, PhD 1 , Mahesh V. Patel, PhD 1 1 1 Lipocine Inc., Salt Lake City, UT; 2 Saint Joseph’s University,
Slide 2: COVID-19 Epidemiology: Gender Differences on Infection and Outcomes
COVID - 19 Epidemiology Gender Differences on COVID - 19 Infection and Outcomes 2 Sleep Apnea Chemotherapy Injury Age > 65 Hypertension Diabetes CAD COPD Obesity Malignancy Asthma CKD COVID - 19 Hypogonadism 0 10 20 30 40 50 60 70 COVID Cases COVID Deaths % Male Female • Despite being infected at eq
Slide 3: Low T at Hospital Admission Predicts Poor Clinical Outcomes
Low T at Hospital Admission Predicts Poor Clinical Outcomes • ~80% of men who die of COVID - 19 have low testosterone at hospital admission 5 • Serum total testosterone level significantly decrease from pre - COVID - 19 levels 6 • Men with lower T are at higher risk for ARDS 4,5,7 and death 4,5,6 0
Slide 4: Low T at Hospital Admission Correlates with Markers of Increased Disease Severity
Low T at Hospital Admission Correlates with Markers of Increased Disease Severity • T levels inversely correlate with cytokine storm including levels of: • VEGF • IFN - γ • IL - 2 • IL - 6 • CRP • TNF - α • D - dimer • LDH • Neutrophil count 4 4, 5, 6, 7
Slide 5: COVID-19 Causes Damage to Testis
COVID - 19 Causes Damage to Testis • SARS - CoV and MERS cause orchitis 9, 14 • Most (but not all 15 ) studies have failed to isolate SARS - CoV - 2 RNA from sperm, testis 10, 11, 12, 13 • Men with COVID - 19 experience elevated LH, decreases in Leydig cell number 8, 8 • Hospitalized COVID - 19 men
Slide 6: Lipocine Oral T: Potential as COVID-19 Therapy
Lipocine Oral T: Potential as COVID - 19 Therapy General effects of T therapy in Hypogonadal Men • T therapy improves lung function (COPD) 18 - Rapid, non - genomic relaxation of ASM 23 • T therapy reduces inflammatory markers while promoting T and B - cell production, function 19, 24, 31 -40 -20 0
Slide 7: Lipocine Oral T: Potential as COVID-19 Therapy
Lipocine Oral T: Potential as COVID - 19 Therapy • Rapidly restores T levels to normal range • Demonstrates anti – inflammatory and anti – fibrotic effects on the lungs » Including decreasing TNF - α , IL - 6, IL - 8, MCP - 1, and CD68 Days after Oral T Initiation 7 • Reduces elevated liver injury m
Slide 8: Conclusions
Conclusions • Men are more susceptible to severe COVID - 19 and death • Men with COVID - 19 have low T, elevated LH, damaged Leydig cells, and elevated cytokines • T therapy in hypogonadal men improves lung and vascular function, is immunomodulatory, reducing cytokines and promoting B and T cell res
Slide 9: References
1. Ng, J et al., COVID - 19 Mortality Rates by Age and Gender: Why is the Disease killing more Men than Women? RGA White Paper 2. Metro.co.uk l Source: Global Health l 50/50 3. CDC.gov 4. Rastrelli, G et al., Low testosterone levels predict clinical adverse outcomes in SARS - CoV - 2 pneumonia patie
Slide 10: References
13. Guo, L et al., Absence of SARS - CoV - 2 in semen of a COVID - 19 patient cohort. Andrology, 2020. 14. Abobaker, A et al., Does COVID - 19 affect male fertility? World J Urol, 2020. 15. Li, D et al., Clinical Characteristics and Results of Semen Tests Among Men With Coronavirus Disease 2019. Inf
Slide 11: References
References 26. Mann, D et al., Neonatal treatment with luteinizing hormone - releasing hormone analogs alters peripheral lymphocyte subsets and cellular and humorally mediated immune responses in juvenile and adult male monkeys. J Clin Endocrinol Metab, 1994. 27. Cain, D and Cidlowski, J, After 62 y
Slide 12: Appendix
Appendix 12
Slide 13: Testosterone Normalizes, Dexamethasone Suppresses: Immunomodulation vs Immunosuppression
Testosterone Normalizes, Dexamethasone Suppresses: Immunomodulation vs Immunosuppression • Dexamethasone suppresses innate and adaptive immune system » Including B cells and CD4+, CD8+ T cells 27 » Greatest benefit for patients with late disease stage 29, 30 » Need to avoid immunosuppression during
Slide 14: What About ACE2 and TMPRSS2?
What About ACE2 and TMPRSS2? • TMPRSS2 – protease involved in spike priming » Expression known to be driven by androgens in the prostate » Data elsewhere is mixed/ negative » Androgens do NOT increase pulmonary TMPRSS2 expression, and do NOT increase susceptibility to virus in multiple pulmonary mod