037 Is Oral Testosterone a Potential Treatment for COVID-19 in Men?

Introduction

Over 4 million cases of SARS-CoV-2 infections and more than 150,000 COVID-19 deaths have been recorded in the US alone. While COVID-19 infection rates of men and women are comparable, men are developing severe symptoms and dying at a significant higher rate than women. Men are 2.5x more likely to develop Acute Respiratory Distress Syndrome (ARDS), and 1.5-3x more likely to die from COVID-19 compared to women. Moreover, men with comorbidities commonly associated with lower testosterone are at a greater risk for severe disease and death. This presentation will discuss evidence that men with low testosterone (T) are at an increased risk for poor COVID-19 outcomes and the rationale of using an oral testosterone therapy, for COVID-19.

Objective

1) To summarize recent publication data on the role T plays in the mortality discrepancy between men and women and 2) To evaluate whether LPCN 1149, once a day oral testosterone, is suitable to treat men with COVID-19.

Methods

A literature search on the possible mechanisms and clinical evidence concerning T levels in COVID-19 patients was performed.

Results

Key clinical evidences suggest that low T levels may play an important role on the clinical outcomes of COVID-19 in men. A recent clinical study investigating T levels in men with COVID-19 found more than 80% of men who died due to COVID-19 had low bioavailable T levels at the time of hospital admission. Those with severe ARDS had acutely depressed total T compared to patients who did not exhibit severe ARDS (total T: 63 ng/dL vs. 202 ng/dL). The mean total T levels for men who required invasive ventilation was 29 ng/dL, whereas those who were discharged from the ICU had mean total T of 254 ng/dL at the time of ICU admission. In comparison to other routes of testosterone administration, oral testosterone therapy may be the most convenient and suitable for acute treatment of COVID-19 both inpatient and outpatient settings. Oral T can rapidly increase the transiently reduced testosterone. This may prevent unfavorable COVID-19 outcomes through multiple mechanisms of action and its effects on the lung, immune cells, and liver. T therapy has pulmonary effects, including direct, non-transcriptional effects on airway smooth muscle and potentiating the relaxing effect of β2 agonists. In addition, T is known to induce the angiotensin-converting enzyme 2 (ACE2) expression, an important lung protective enzyme, to induce erythrocyte production, to increase hemoglobin and hematocrit, and thereby to improve oxygen carrying capacity. T is a known immunomodulator and exhibits an inhibitory effect on the expression of various cytokines including C-reactive protein, TNF-α, IL-1, and IL-6. Finally, its anabolic effect may prevent the loss of skeletal muscle mass seen in the hospitalized patients, particularly in the presence of low T.

Conclusions

Oral testosterone with the goal of achieving physiological T levels should be evaluated in clinical trials of COVID-19, particularly in men who are found to have T deficiency.

Disclosure

Work supported by industry: yes, by Lipocine Inc. A consultant, employee (part time or full time) or shareholder is among the authors (Lipocine Inc).