01/25/2017 01:46 pm ET Updated Jan 26, 2018

When Men and Women Differ

By Drs. David Niesel and Norbert Herzog

Besides the obvious physical differences, science is beginning to tease out some significant biological differences between men and women that have implications for women's health. A call to action was the measles vaccine that the World Health Organization suddenly had to withdraw after the deaths of infant girls increased but not boys. The cause remains unclear, but it served as a wakeup call to science to pay attention to gender differences when evaluating or testing drugs or vaccines.

Fifteen years ago, it was discovered that women infected with HIV, are usually infected by many different forms of the virus but men just by one. It is unclear why this is so. This has obvious implications in the design of a universal HIV vaccine.

Women also tend to suffer from more severe symptoms of the flu in spite of having fewer viruses in their blood during the infection. It is theorized that women mount more of an immune response leading to more severe symptoms. In mice, castrated males become more sensitive to flu infection, so hormones must play a role.

Many studies avoid female animals because menstrual cycles and pregnancy introduce a huge complicating factor. Only a few studies have identified differences in the women after infections or their immune responses to them. Recently scientists have begun to determine some of the mechanisms accounting for these differences. In one such study, when a tuberculosis vaccine was given to Gambian infants, it suppressed production of an anti-inflammatory protein in girls but not in boys. Without this protein, girls mounted a better immune response perhaps making the vaccine more effective.

The hormone estrogen improves our cells ability to resist viruses while testosterone suppresses it. Only female nasal cells treated with estrogen resisted infection with the flu virus. Why? A protein called TLR 7 is vital in the defense against viruses. TLR7 detects when a virus infects a cell and initiates a series of signaling events that activates the immune response against the virus. Interestingly, the gene for TLR7 is on the X-chromosome. Cells in women have two X chromosomes, and men just one. While one of X chromosomes in each female cell is inactivated, a likely conclusion is that the amount of TLR7 produced should be the same between the sexes. However, some genes on the inactivated X chromosome escape this inactivation which could be the explanation in this case.

A study is underway comparing 40 adults undergoing sex change operations. If female hormones are responsible for the stronger immune responses, then transgender women should mount better immune responses but this should not occur in transgender men. These results will be illuminating. Both US and European science agencies now have rules requiring reporting the sex of animals used in research studies. There are still too few studies that evaluate the differences between men and women in the way they respond to drugs or to infections and the immune responses to them. It should not be assumed that men and women always respond the same which could improve treatment choices and hence outcomes. For all that we are alike, the harder we look, the more differences we will find.

Medical Discovery News is hosted by professors Norbert Herzog at Quinnipiac University, and David Niesel of the University of Texas Medical Branch. Learn more at