6479 Acute Estradiol and Progesterone Therapy In Hospitalized Adults With Moderate COVID-19: A Randomized Control Trial

Abstract Disclosure: D. Lovre: Research Investigator; Self; Novo Nordisk, Corcept Therapeutics. K.M. Bateman: None. L.Y. Saltzman,: None. M. Qadir: None. F. Mauvais-Jarvis: None. Background and Objective: COVID-19 outcomes are less severe in women vs men. Experimental studies show that estradiol (E2) and progesterone (P4) produce anti-inflammatory immune responses and immune tolerance and enhance antibody production. The effect of E2 and P4 combination on COVID-19 severity is unknown. The aim of the study was to evaluate the efficacy of a short systemic E2/P4 combination in mitigating COVID-19 severity in hospitalized men and women. Methods: Phase 2, double blind, placebo-equivalent controlled, single center trial of ten participants (men and women) who were hospitalized for COVID-19, with scores 3 to 5 on the 9-point World Health Organization (WHO) ordinal scale for clinical improvement. Participants were randomized into two arms and treated for five days: 1) E2 Cypionate (5 mg IM once) and micronized P4 (200mg, PO daily); and 2) Placebo-equivalent (normal saline (1ml, IM once) and folate (400mcgs, PO daily), in addition to standard of care (SOC). The primary outcome was the proportion of patients improving to scores 1 or 2 on the WHO scale on the day of discharge. Secondary outcomes included length of hospital stay (LOS), days on oxygen therapy (DOT), readmission rates (RR), adverse events (AEs) and change in inflammatory biomarkers assessed by untargeted proteomics. Findings: There were no significant differences between the treatment groups in COVID-19 severity by WHO score, LOS, DOT, RR or AEs. Patients in the E2/P4 arm exhibited a decrease in inflammatory biomarkers of respiratory and gastrointestinal disease (GI) and significant change in immune and inflammatory responses. Conclusions: Use of short-term systemic E2/P4 is associated with decrease in biomarkers of respiratory and GI disease inflammation and change in biomarkers of immune and inflammatory response. Presentation: 6/3/2024