Progesterone May Protect Women Against Dangerous Effects of Influenza

The World Health Organization credits contraception with preventing pregnancy-related health risks in women, reducing adolescent pregnancies, and lowering infant mortality rates. What researchers are now discovering is that hormonal contraceptives containing progesterone may also protect women against influenza infections and repair lung damage caused by inflammation.

Progesterone (P4)—a hormone naturally produced by the ovaries—often, along with estrogen, is a main component of the hormonal contraceptives taken by women around the world. Researchers have noted progesterone’s immunomodulatory effects, including the hormone’s ability to decrease inflammation and induce the immune system’s anti-inflammatory response. Studies have shown how progesterone influences the outcome of some sexually transmitted infections, but a team of doctors from the Johns Hopkins Bloomberg School of Public Health and School of Medicine wanted to study the effects of the hormone on viral infections outside of the reproductive tract. Their new paper, published in the journal PLOS Pathogens, offers a look at how progesterone treatment can protect women against the influenza A virus and other infectious diseases.

Seasonal infections due to influenza fluctuate greatly in length and severity from year to year, and even in a so-called “good flu season,” the virus causes many illnesses, hospitalizations, and deaths. While it’s difficult to track flu-related deaths, the Centers for Disease Control and Prevention (CDC) says that from the 1976-1977 flu season to the 2006-2007 flu season, anywhere from 3,000 to 49,000 individuals died each season. The contagious respiratory infection causes symptoms such as fever, cough, sore throat, runny nose, headaches, body aches, and fatigue. While many cases resolve within several days, complications can develop and most often occur in young children, adults aged 65 years and older, and those with compromised immune systems.

Influenza viruses work by infecting respiratory epithelial cells and inducing the production of proinflammatory cytokines and chemokines. The T-cells released in our immune response and needed to clear an influenza virus infection can trigger inflammation in the body and lead to lung tissue damage. This immunological protection is a delicate balance, note the authors of the study, between inflammatory responses generated to control virus replication and eliminate virus-infected cells and the responses that mediate the repair of damaged areas of the lung. Cell repair involves a complex array of cytokines, chemokines, growth factors, and extracellular matrix proteins that remodel tissue after acute lung injury caused by influenza.

With a growing body of evidence on the inflammation-reducing benefits of progesterone and estrogen, the researchers in this study administered the hormone to female mice infected with influenza A as well as those given a mock virus. They used subcutaneous pellets containing progesterone to give the mice a continuous hormone dose higher than the normal physiological range. The influenza A-infected mice had a higher expression of progesterone receptors in the lungs than the infected mice given a placebo. While the hormone did not render the female mice more resistant to influenza infection, nor cause a decrease in viral replication, the researchers’ examination of pulmonary tissue found that it did reduce inflammation and damage. Influenza-caused damage to the lung endothelium and epithelium results in vascular leakage into the air spaces, which can be measured by the amount of protein concentration in bronchoalveolar lavage fluid, and mice treated with progesterone had lower levels of that protein than mice given a placebo. The researchers also noted that the progesterone-treated mice showed greater cell proliferation in airway epithelial cells promoted by the epidermal growth factor, AREG.

The findings in this research indicate that progesterone promotes a repair environment in the lungs in response to influenza infection and also accelerates long-term pulmonary recovery. The study researchers note that while they haven’t conducted studies in women, there are ways to measure how hormonal contraceptives that include progesterone may impact the health of women with influenza. “Assessment of recovery, inflammation, and outcome of influenza based on hormone contraceptive use would provide useful insights into whether the protective effects of progesterone apply to women,” says Sabra L. Klein, PhD, one of the study’s authors. “The Johns Hopkins Center of Excellence in Influenza Research and Surveillance conducts influenza surveillance in Baltimore, Maryland as well as in Taipei, Taiwan. Hormone contraceptive and hormone replacement use is on the questionnaire provided to patients who enroll in our studies. We just may be able to answer these questions in women.”

While progesterone shows some promise in limiting the effects of an influenza infection, the CDC says that the first and most important step of protection against the virus is getting a flu vaccination every year, along with preventive actions like handwashing and avoiding individuals who are sick.