Progesterone therapy may improve clinical outcomes for COVID-19 male patients

COVID-19 has a disproportionate effect on men compared to women, raising the possibility that hormones such as progesterone may improve clinical outcomes for certain men hospitalized with the disease. New research from Cedars-Sinai was published online in the journal Ciste supports this view.

The pilot clinical trial, which included 40 males, is believed to be the first published study to use progesterone to treat COVID-19 male patients whose lung functions are compromised by the coronavirus. While the conclusions are promising, larger clinical trials are needed to establish the potential of this experimental treatment, the researchers said.

The study was inspired by multiple reports that men are at greater risk for mortality and serious illness from COVID-19 than women, according to Sara Ghandehari, MD, director of Pulmonary Rehabilitation at Cedars Women’s Lung Guild Institute -Sinai and chief investigator for the trial.

As an ICU doctor, I was struck by the gender difference among COVID-19 patients who were critically ill, living in hospital and in need of ventilation. “

Sara Ghandehari, MD, Director of Pulmonary Rehabilitation, Women’s Association Lung Institute, Cedars-Sinai

In addition, some published studies had shown that premenopausal women, who generally have higher progesterone levels than postmenopausal women, who have lower progesterone levels, had lower COVID-19 infection. While the bodies of men and women naturally produce progesterone, women make much more of the hormone during their reproductive years.

Protective effect of female hormones

Ghandehari acknowledged that the gender differences in disease outcomes may be due, in part, to the protective effect of female hormones. In particular, preclinical studies elsewhere have indicated that progesterone had certain anti-inflammatory properties. This finding may suggest progesterone may be useful in suppressing an sometimes lethal immune response, known as a “cytokine storm,” which can exacerbate lung damage and attack on other organs in COVID-19 patients.

For the Cedars-Sinai clinical trial, conducted from April through 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 the usual medical care at the time for the infection. Patients in the experimental group received routine care in addition to a 100 milligram injection of progesterone twice daily for five days while in hospital. Both groups were evaluated daily for 15 days or until discharge from hospital.

Study results

The study showed that, compared with the control group, patients in the progesterone-treated group received a median score 1.5 points higher on a seven-point scale of normal clinical status after seven days. The scale ranged from a high of 7 (“no hospital, no restrictions on activities”) to 1 (“death”). Although the progesterone group as a whole also had fewer hospital days and a lower need for additional oxygen and mechanical ventilation, the differences between the two groups in these specific regions were not significant. statistical.

There were no serious adverse events, including life-threatening events, as a result of progesterone administration. Two deaths, one in each group, died during the 15-day study period, and none were due to progesterone.

“While our findings are encouraging for the potential use of progesterone to treat men with COVID-19, there were significant limitations in our study,” Ghandehari said.

She noted that the sample size was relatively small and consisted mainly of white, Hispanic, and obese patients with a moderate burden of comorbidities, which increases the risk for worse outcomes. Further, although the clinical trial was randomized and controlled, it was unrelated – meaning that the investigators, patients, and treating physicians knew who received the experimental treatment.

“Further research is needed in larger, more heterogeneous populations, including postmenopausal women and at other treatment centers, to establish the degree of clinical efficacy and to address any other potential safety concerns. to evaluate this approach, “said Ghandehari, who is also deputy director of the Lung Transplant Program at Cedars-Sinai.

Progesterone is approved by the U.S. Food and Drug Administration (FDA) for use in fertility-related conditions in women but not for the modeling of inflammatory, immunologic-based responses. The FDA approved this particular use for the purpose of Cedars-Sinai clinical trial under a new drug research application.