Progesterone in Addition to Standard of Care vs Standard of Care Alone in the Treatment of Men Hospitalized With Moderate to Severe COVID-19
MD Sara Ghandehari, MD Yuri Matusov, MD Samuel Pepkowitz, PhD Donald Stein, MD Tamana Kaderi, MD Divya Narayanan, MD Josephine Hwang, MD Stephanie Chang, MD Robert Goodman, MS Heli Ghandehari, MS James Mirocha, MS Catherine Bresee, MD Victor Tapson, MD Michael Lewis
Chest, doi:10.1016/j.chest.2021.02.024
BACKGROUND: Severity of illness in COVID-19 is consistently lower in women. A focus on sex as a biological factor may suggest a potential therapeutic intervention for this disease. We assessed whether adding progesterone to standard of care (SOC) would improve clinical outcomes of hospitalized men with moderate to severe COVID-19. RESEARCH QUESTION: Does short-term subcutaneous administration of progesterone safely improve clinical outcome in hypoxemic men hospitalized with COVID-19? STUDY DESIGN AND METHODS: We conducted a pilot, randomized, open-label, controlled trial of subcutaneous progesterone in men hospitalized with confirmed moderate to severe COVID-19. Patients were randomly assigned to receive SOC plus progesterone (100 mg subcutaneously twice daily for up to 5 days) or SOC alone. In addition to assessment of safety, the primary outcome was change in clinical status on day 7. Length of hospital stay and number of days on supplemental oxygen were key secondary outcomes. RESULTS: Forty-two patients were enrolled from April 2020 to August 2020; 22 were randomized to the control group and 20 to the progesterone group. Two patients from the progesterone group withdrew from the study before receiving progesterone. There was a 1.5point overall improvement in median clinical status score on a seven-point ordinal scale from baseline to day 7 in patients in the progesterone group as compared with control subjects (95% CI, 0.0-2.0; P ¼ .024). There were no serious adverse events attributable to progesterone. Patients treated with progesterone required three fewer days of supplemental oxygen (median, 4.5 vs 7.5 days) and were hospitalized for 2.5 fewer days (median, 7.0 vs 9.5 days) as compared with control subjects. INTERPRETATION: Progesterone at a dose of 100 mg, twice daily by subcutaneous injection in addition to SOC, may represent a safe and effective approach for treatment in hypoxemic men with moderate to severe COVID-19.
Author contributions: S. G., Y. M., S. P., T. K., D. N., J. H., S. C., V. T., and M. L. take responsibility for all content of the manuscript, the integrity of the data, and the accuracy of the data analysis. Concept and design: S. G., Y. M., S. P., D. S., H. G., J. M., V. T., M. L.; acquisition, analysis, or interpretation of data: S. G., Y. M., S. P., D. S., T. K., D. N., J. H., S. C., C. B., R. G., H. G., J. M., V. T., M. L.; drafting of the manuscript: S. G., Y. M., S. P., D. S., T. K., D. N., J. H., S. C., R. G., H. G., C. B., J. M.; critical revision of the manuscript for important intellectual content: S. G., Y. M., D. S., R. G., V. T., M. L.; statistical analysis: H. G., C. B., J. M.; obtaining of funding: S. G.; regulatory compliance: S. G. Role of sponsors: IBSA provided the study drug and provided partial financial support for this investigator-initiated study. IBSA did not oversee the study and has not participated in trial design, patient recruitment, data collection, analysis, interpretations, or preparation of this manuscript. Other contributions: The authors thank the patients who altruistically participated in this randomized trial; Heather Jones, MD, and Darina Barnes, PharmD, for providing independent safety review; S. Ananth Karumanchi, MD, for guidance and review of the manuscript; members of the Cedars-Sinai Biobank for handling specimens; members of the Cedars-Sinai research pharmacy for dispensing the study drug; Vanessa Vasco and other members of the..
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