Estrogen Protective Against Flu Virus in Women But Not Men, Study Suggests

Finding could offer additional benefits to hormone replacement therapy or infertility treatment

Estrogen dramatically reduced the amount of flu virus that replicated in infected cells from women but not from men, a new study by researchers at the Johns Hopkins Bloomberg School of Public Health shows.

The findings, reported online last week in the American Journal of Physiology - Lung Cellular and Molecular Physiology, suggest a protective advantage to the quintessential female hormone that naturally circulates in women’s bodies, as well as artificial forms given for hormone replacement therapy and estrogen-like chemicals found in the environment.     

Recent studies have shown that estrogen can hamper replication of viruses including HIV, Ebola and hepatitis, which can lessen an infection’s severity and make an infection less likely to spread to other people. But the new study’s leader, Sabra L. Klein, Ph.D., an associate professor in the Departments of Molecular Microbiology and Immunology and Biochemistry and Molecular Biology at the Bloomberg School, says it was unknown whether estrogen might have the same effect on the flu virus.

To investigate, she and her colleagues collected cells from the nasal passage — typically the first cells in the body to get infected with the flu — from female and male volunteers. The researchers exposed batches of these cells to different types of estrogens, including normal levels of naturally occurring estrogen, different types of selective estrogen receptor modulators (SERMs, synthetic estrogen-like chemicals used for hormone replacement therapy and infertility treatment, among other uses) or bisphenol A, an estrogen-like chemical found in many plastics. They then exposed cells to the influenza A virus, a variant of the flu virus that circulates each year during the flu season.

Tests showed that female cells that received estrogens, including some types of SERMs and bisphenol A, had marked reductions of viral replications — nearly 1,000-fold less compared to those that hadn’t been exposed to these hormones. Further investigations showed that the hormones that caused this striking effect act on estrogen receptor beta, one of two types of receptors for estrogen inside cells.

Klein explains that even though men produce estrogen, their cells have far fewer receptors for the hormone. That might be why estrogen didn’t have the same protective effects against flu virus replication in cells from men.

When Klein and her colleagues looked for a mechanism behind estrogen’s protective effect, they found that binding to estrogen receptor beta decreased the activity of more than 30 genes involved in cell metabolism, slowing the metabolic activity of these cells and potentially preventing them from manufacturing viral particles.

Klein notes that because hormone levels cycle in pre-menopausal women, it’s unlikely that there’s a population-wide effect in protecting this group against the flu. But, she says, the new findings suggest that hormones that women already take for contraception, hormone replacement therapy, infertility treatments or other medical uses could play a powerful role in reducing infection. She doesn’t suggest starting hormone therapies for this reason, however, because estrogens can have other biological effects ranging from strengthening bones to increasing risks for some types of cancer.

“If women are taking estrogen-like hormones for other reasons, an added benefit might be less susceptibility to influenza during the flu season,” Klein says. The findings could be particularly important for elderly women, she adds, since this population is most susceptible to severe influenza.

“Being on hormone replacement therapy could be one way to mitigate the severity of this disease, which is exciting, simple and cheap,” she says. “While the decision to take hormone therapy should always depend on a patient’s history and include discussion with their care providers, our study shows another potential benefit to this hormone.”

“Estrogenic compounds reduce influenza A virus replication in primary human nasal epithelial cells derived from female, but not male, donors” was written by Jackye Peretz, Andrew Pekosz, Andrew P. Lane and Sabra L. Klein.

This research was supported by grants from the Center for Alternatives to Animal Testing at the Johns Hopkins Bloomberg School of Public Health, the National Institutes of Health’s National Institute on Aging (R01AI097417, R01AI72502 and T32 AI007417) and the U.S. Department of Health and Human Services (HHSN272201400007C).

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Media contacts for the Johns Hopkins Bloomberg School of Public Health: Barbara Benham at 410-614-6029 or bbenham1@jhu.edu and  Stephanie Desmon at 410-955-7619 or sdesmon1@jhu.edu.