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Is progesterone capable of protecting men from severe COVID-19?

A man receiving covid-19 test
Is progesterone capable of protecting men from severe COVID-19?
  • Men are more likely than women to experience serious COVID-19 and die.
  • In a small-scale pilot study, researchers looked to see whether injectable progesterone benefited men with moderate-to-severe COVID-19.
  • After 7 days, those who got progesterone had better health results.
  • According to the results, further research is needed to establish progesterone’s safety and efficacy in treating COVID-19 in a larger, more diverse population.

Men are 2.4 times more likely than women to die from COVID-19. A dynamic interplay of psychosocial, behavioral, and biological influences may be to blame for the difference.

Men, for example, are more likely than women to participate in higher-risk habits, such as increased tobacco and alcohol use. They also have lower rates of social isolation, handwashing, and mask use.

Men are also less likely to seek medical treatment proactively and have a higher prevalence of health problems related to lower COVID-19 outcomes.

Immune variations between men and women

Females have stronger immune responses than males, which may be related to variations in sex chromosome chromosomes and sex hormones like progesterone.

Several immune cell types express progesterone receptors, which may help premenopausal women minimize inflammation.

In females, progesterone is released by the ovaries, and in males, it is produced by the adrenal gland and testes. Males and postmenopausal females, on the other hand, have much lower concentrations.

COVID-19-positive premenopausal women spend less time in the hospital, according to previous studies. They are also less likely than postmenopausal women to need respiratory assistance.

Progesterone can reduce the exaggerated immune response, or “cytokine storm,” that causes severe lung injury and can lead to death in people infected with SARS-CoV-2.

In the United States, progesterone is currently approved to treat infertility, the absence of menses or amenorrhea, and abnormal uterine bleeding.

Scientists infected mice with influenza A in one study. When the animals were given progesterone, the inflammation in their lungs was decreased, and they recovered faster.

This observation prompted researchers at Cedars-Sinai Medical Center to perform a randomized controlled pilot trial to determine progesterone’s efficacy and safety in men hospitalized for COVID-19. Their findings were published in the journal Chest.

Testing progesterone

Dr. Sara Ghandehari, director of pulmonary rehabilitation at the Women’s Guild Lung Institute, assistant director of the Cedars-Sinai Medical Center’s Lung Transplant Program, and the trial’s principal investigator, says:

“As an [intensive care unit] doctor, I was struck by the [sex] disparity among COVID-19 patients who were very sick, remained in the hospital, and needed ventilators.”

The research enrolled 42 men aged 18 and older who were hospitalized with moderate-to-severe COVID-19 and low oxygen levels between April 27 and August 5, 2020.

The participants were divided into two groups: an experimental and a control group. They gave the experimental group a progesterone injection twice daily under the skin with normal medical treatment for 5 days, then gave the control group only regular medical care.

The participants were tested every day for 15 days or before they were discharged. On days 7 and 15, the scientists followed up with phone calls or video research visits for those who were discharged.

The study design enabled the researchers to offer progesterone to participants in the control group who were worsening or not improving by day 7.

Optimistic results

The findings of 18 progesterone group participants and 22 control group participants were analyzed, with two progesterone group participants withdrawing from the trial. Since nine patients in the control group were not progressing or deteriorating, the researchers gave them progesterone.

The research used a scale of 1–7 to measure clinical status, with a higher score suggesting a better clinical outcome. After 7 days, participants in the progesterone group scored 1.5 points higher on the clinical status scale than those in the control group.

The progesterone-treated participants needed 3 fewer days of supplemental oxygen and 2.5 fewer days in the hospital than the control group, but the difference was not statistically important.

Progesterone was not related to any significant side effects or an increased risk of blood clots in the sample.

The study’s primary drawback was its limited scale. Also, patients, providers, and researchers all knew who was in the control group and who was in the experimental group, which may have biased the study results.

Furthermore, the majority of the participants were white and Hispanic, with pre-existing conditions like diabetes, hypertension, and obesity, both of which are risk factors for extreme COVID-19 disease.

The study’s generalizability to other populations may be limited due to the lack of diversity among study participants.

“Further study in larger, more heterogeneous populations, including postmenopausal women and at other treatment centers is important to determine the degree of clinical effectiveness and to evaluate any other possible safety issues of this treatment approach,” says Dr. Ghandehari.