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Professor Explores How XX and XY Matter in Medicine

September 3, 2009 – No question about it, says Kathryn Sandberg, women are much more complex than men – in a purely biological sense, she adds.

That complexity can lead to different reactions to medication between men and women, something Sandberg, director of Georgetown’s Center for the Study of Sex Differences in Health, Aging and Disease, currently studies.

The biological complexity of women may surprise people, Sandberg says, because men have two different sex chromosomes (an X and Y) while women have just one (two copies of the X chromosome) in their cells. That suggests that men have something women don’t have when it comes to genes. 

And it’s true: men are men because their Y chromosome contains the all-powerful SRY gene that dictates development of male testes. Women are the “default status” – the being that develops when an SRY gene is absent.

But that is not the whole story, Sandberg says. While one X chromosome is “silenced” within each female cell, such control is imperfect.

Battle of the Sexes Extends to Health

All of this is important, Sandberg says, because “biological sex vastly influences a person’s medical experience from cradle to grave. Women and men exhibit big differences in susceptibility to various diseases. They experience symptoms like pain in different ways, and they can react differently to drugs and have very different outcomes.”

The scientist suspects that nine out of 10 drugs pulled off the market due to adverse events are because women do not tolerate the drugs as well as men. While the National Institutes of Health has said women must be included in federally funded drug trials, Sandberg notes that the mandate does not apply to phases where efficacy and side effects are studied.

Given this, Sandberg and her center are dedicated to sex difference research and educating researchers nationwide about the importance of considering the role of biological sex in all phases of drug testing.

Menopause, Mice and High Blood Pressure

The researcher currently studies menopause’s effect on blood pressure. Menopausal women often have pressure levels exceeding those of men, but its cause is not well understood.

Sandberg’s team employs a mouse model to study studying menopausal mice and high blood pressure. Some of the male mice do not have an SRY gene, which normally causes testes growth, thereby resulting in XY female mice. To mimic menopause, ovaries were removed from both XY and XX females, and her laboratory has discovered that XX mice developed higher blood pressure than the XY females in an induced model of hypertension.

“These findings raise the possibility that gene expression in the XX sex chromosomal complement has an adverse effect on blood pressure once menopause begins. It may not be active before menopause because ovarian hormones could be blocking or masking it,” she says. “No one has ever suspected such a scenario.”

“If our research leads us to a greater nuanced understanding of hypertension in women, we may be able to develop a targeted treatment approach,” Sandberg adds. “And what we learn about women may be applicable to men – even if they are less complex.”

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