A new study may explain why flu appears to hit men harder than women. Researchers who tested various forms of the female sex hormone estrogen – which is also present in men – on nasal cells from men and women, found the compounds reduced virus replication in the female but not the male cells.

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New research may explain why flu seems to hit men harder than women – it finds that estrogen weakens the virus in nasal cells from female but not male donors.

The researchers – led by Sabra Klein, an associate professor at Johns Hopkins Bloomberg School of Public Health in Baltimore, MD – report their findings in the American Journal of Physiology – Lung Cellular and Molecular Physiology.

Viruses make us ill when they invade our cells and use their machinery to make copies of themselves. The copies spread to other cells, setting up a chain reaction that leads to disease and also infection of other people.

Generally, the fewer copies of itself the virus makes, the less severe the disease and the lower the chances of it spreading to new hosts, says Prof. Klein.

Together with her colleagues, she tested the effect of the female sex hormone estrogen on the influenza A virus – one of the types of flu virus that spreads in people and causes seasonal flu epidemics.

They carried out the tests in nasal cells – the cells that the virus primarily infects – gathered from men and women.

The researchers cultured and then exposed the cells to the flu virus and various forms of estrogen, including: estradiol (the primary form of the female sex hormone in the body); bisphenol A (a synthetic compound that mimics estrogen); and selective estrogen receptor modulators (SERMs) – compounds that act like estrogen and are used for hormone therapy.

The results showed that estradiol, raloxifene (an SERM) and bisphenol A reduced virus replication in the female – but not the male – cultured nasal cells.

The researchers also noticed that the estrogens exerted their antiviral effects through the estrogen receptor beta. Receptors are “gatekeeper” proteins that only allow entry to cell-stimulating molecules that can bind to them.

Prof. Klein says other studies have already shown that estrogen has antiviral effects on HIV, Ebola and hepatitis viruses. But there are two reasons why this new study is unique, as she explains:

“First, we conducted our study using primary cells directly isolated from patients, allowing us to directly identify the sex-specific effect of estrogens. Second, this is the first study to identify the estrogen receptor responsible for the antiviral effects of estrogens, bringing us closer to understanding the mechanisms mediating this conserved antiviral effect of estrogens.”

The new findings also support those of animal studies that have shown the antiviral effects of estrogen on the flu virus.

It may be difficult to see this protective effect in premenopausal women because estrogen levels go up and down in the menstrual cycle. However, it could mean that women on certain kinds of birth control or those receiving hormone replacement for menopausal symptoms may be better protected during seasonal flu epidemics, notes Prof. Klein, who concludes:

We see clinical potential in the finding that therapeutic estrogens that are used for treating infertility and menopause may also protect against the flu.”

Meanwhile, Medical News Today recently learned that scientists have identified a host protein called ANP32A that allows the flu virus to replicate in host cells.