Female sex hormones have a profound effect on susceptibility to the herpes simplex virus

Two McMaster University studies, to be published in the Journal of Virology, show that sex hormones have a profound effect on susceptibility of female mice to the herpes simplex virus, type 2 (HSV-2 ), one of the most common sexually transmitted diseases.

Charu Kaushic, assistant professor and supervisor of the studies, says the implication of this work is quite significant. “The research clearly shows, and reaffirms previous research, that in female mice, sex hormones have a profound effect on susceptibility to sexually transmitted infections as well as on the body's defense mechanisms against them.”

One of the many implications of these findings she says, is that if future studies can figure out that women too, like mice, are protected in primary exposure by estradiol, contraceptive creams could be formulated that would prevent herpes virus infection before they could start. Additionally she says, if they were designing a vaccine trial against HSV-2 and if the mice results hold true for women, they could suggest vaccination protocols under combination hormone therapy to get the best benefit from the vaccine.

Work in this area is important because one in every four sexually active adults is seropositive for HSV-2 and women are much more susceptible than men.

“The results directly indicate that the hormonal conditions that provide protection against primary exposure to sexually transmitted viral infections may be very different than those that may be useful in vaccination strategies,” said Kaushic.

“There is of course the flip side to this as well. Our studies in mice and in fact a number of clinical studies as well show that women who use Depo-provera, a progesterone based injectable contraceptive, have particularly high susceptibility to sexually transmitted infections, including HIV-1 and HSV-2. We do not understand why, and our hope is that by doing these kind of mouse studies, we can understand the mechanisms.”

In the first study, female mice received either the hormone estradiol or progesterone, a combination of both, or nothing at all prior to exposing them to the herpes virus. Both estradiol and progesterone are natural hormones found in the body.

The estradiol-treated mice were protected 100 percent, whereas the progesterone-treated mice and mice that didn’t receive any hormones, showed extensive infection, and additionally, the progesterone-treated mice had increased inflammation and were more susceptible to the virus. The mice treated with a combination of the two hormones, estradiol and progesterone, were protected, but only if the virus doses were weakened.

In the second study, just like in the first study, mice were treated with hormones but, before being exposed to the real herpes virus, they received a vaccine.

Surprisingly, unlike in the first study, the progesterone-treated mice and the mice that received no hormones were the most protected. About half the mice in the combination hormone group were also protected and the estradiol-treated group was not at all protected. Similar studies confirmed that a combination of the hormones estradiol with progesterone provided the best protection in vaccinated mice.

“These studies add to the growing evidence that we need to promote more gender-specific medical approaches in future,” she said. “We have to increase awareness in both the medical community as well as the public regarding sexually transmitted diseases and women.”

Extending these findings into clinical studies is the next step. McMaster researchers are currently discussing the design of a study with infectious disease clinicians in Hamilton, which may begin in as early as the next few months. Additionally they will be looking at issues of co-infection with both HIV-1 and HSV-2 which is a big problem clinically.

The two studies were posted online on the Journal of Virology website this week and will be published in the Journal in the March issue.