Progesterone therapy can improve clinical outcomes in male COVID-19 patients
COVID-19 affects men disproportionately compared to women, increasing the possibility that a hormone like progesterone may improve clinical outcomes for certain men in the hospital with the disease. New research from Cedars-Sinai published online in Chest magazine supports this hypothesis.
The 40 male clinical pilot study is believed to be the first published study to use progesterone to treat male COVID-19 patients whose lung functions have been compromised by the coronavirus. Although the results are promising, larger clinical trials are needed to determine the potential of this experimental therapy, the researchers said.
The study was stimulated by several reports that men are at higher risk of mortality and serious illness than women due to COVID-19, said Dr. Sara Ghandehari, director of pulmonary rehabilitation at the Lung Institute of the Women’s Guild at Cedars-Sinai and principal researcher for the process.
As an intensive care doctor, I was impressed by the gender differences between COVID-19 patients who were very ill, stayed in the hospital, and required ventilators. “
Sara Ghandehari, MD, Director of Lung Rehabilitation, Women’s Guild Lung Institute, Cedars-Sinai
In addition, some published studies had shown that pre-menopausal women, who generally had higher levels of progesterone, had less severe COVID-19 disease than post-menopausal women, who had lower levels of progesterone. While the bodies of men and women naturally produce progesterone, women produce much more hormone during their reproductive years.
Protective effect against female hormones
Ghandehari hypothesized that the gender differences in disease outcomes may be due in part to protective effects against female hormones. Preclinical studies elsewhere, in particular, had shown that progesterone had certain anti-inflammatory properties. This finding suggests that progesterone could be useful in dampening a sometimes fatal immune response known as a “cytokine storm,” which can exacerbate lung damage and attack other organs in COVID-19 patients.
For the Cedars-Sinai clinical trial, which ran from April to August 2020, 40 male patients hospitalized with moderate to severe COVID-19 were randomly assigned to one of two groups. Patients in the control group received normal medical care at the time of illness. Patients in the experimental group received standard care plus injections of 100 milligrams of progesterone twice daily for five days during their hospital stay. Both groups were followed up for 15 days or daily until they were discharged from the hospital.
The study showed that patients in the progesterone-treated group had a median 1.5 points higher than the control group after seven days on a standard seven-point clinical status scale. The scale ranged from 7 (“not hospitalized, no restrictions on activities”) to 1 (“death”). Although the progesterone group also had fewer days of hospitalization overall and less need for supplemental oxygen and mechanical ventilation, the differences between the two groups in these specific categories were not statistically significant.
There were no serious adverse events including life-threatening events related to the administration of progesterone. During the 15-day study period, there were two deaths, one in each group, none of which were due to progesterone.
“While our results promote the potential of using progesterone to treat men with COVID-19, our study had significant limitations,” said Ghandehari.
She found that the sample size was relatively small, affecting mostly white, Spanish, and obese patients with moderate exposure to comorbidities, which increased the risk of worse outcomes. Although the clinical trial was randomized and controlled, it was not blinded – meaning the investigators, the patients, and the treating physicians knew who was receiving the experimental treatment.
“In larger, more heterogeneous populations, including postmenopausal women and in other treatment centers, more research is needed to determine the level of clinical efficacy and to assess other potential safety concerns of this treatment approach,” said Ghandehari, who is also deputy director of the lung transplant program on Cedars-Sinai.
Progesterone is approved by the US Food and Drug Administration (FDA) for use in fertility-related diseases in women, but not for modulating immunological inflammatory reactions. The FDA approved this particular use for the Cedars-Sinai clinical trial as part of a new investigational drug application.
Cedars-Sinai Medical Center
S. Ghandehari et al. (2021) Progesterone In Addition To Standard Of Care Compared To Standard Of Care Alone In The Treatment Of Men Admitted To Hospital With Moderate To Severe COVID-19: A Randomized, Controlled Pilot Study. CHEST. doi.org/10.1016/j.chest.2021.02.024.