Women’s Health

In light of the recent launch of the Stanford Center for Health Research on Women and Sex Differences in Medicine (WSDM), I couldn’t help but take notice of a new paper on the topic. In an article in the journal Clinical Chemistry and Laboratory Medicine, Italian researchers have highlighted the “crucial differences between men and women” in five areas: cardiovascular disease, cancer, liver diseases, osteoporosis, and pharmacology.

Arecent journal release provides some examples of the differences:

Typically perceived as a male illness, cardiovascular disease often displays markedly different symptoms among women. While a constricted chest and pain that radiates through the left arm are standard signs of heart attack in men, in women the usual symptoms are nausea and lower abdominal pain. Although heart attacks in women are more severe and complicated, when complaining of these non-specific symptoms women often do not receive the necessary examination procedures, such as an ECG , enzyme diagnostic tests or coronary angiography.

Colon cancer is the second most common form of cancer among men and women. However, women suffer this illness at a later stage in life. Furthermore, colon tumors typically have a different location in women, and they respond better to specific chemical treatments. Gender also has an impact on the patient’s responsiveness to chemotherapy administered to treat cancer, such as colon, lung, or skin cancer. In this way, gender impacts the course of the disease and the patient’s chances for survival.

…While typically viewed as a female disease because of the much higher rate of female patients, osteoporosis also strikes men. The study contends that osteoporosis is too often overlooked in male patients, and it documents a higher mortality rate among men suffering bone fractures.

The authors conclude that “more far-reaching clinical investigations of gender differences are needed in order to eliminate fundamental inequalities between men and women in the treatment of disease.”

Previously: Exploring sex differences in the brain

We’ve written before about the increasing number of breast cancer patients who opt to have both breasts removed, despite having cancer in only one. A CNN.com article today explores the reasons for these rising numbers and mentions a Stanford-developed online support tool, which was designed to help patients weigh their treatment options.

Previously: BRCA patients use Stanford-developed online tool to better understand treatment options, A closer look at preventive breast cancer surgery and Researchers unsure why some breast cancer patients choose double mastectomies

There has been a lot of interest in the Stanford study suggesting that aspirin reduces the risk of melanoma in women; dermatologist Jean Tang, MD, PhD, spent much of her day today discussing the findings with reporters from NPR and the three networks’ evening news programs. Earlier, in a 1:2:1 podcast, Tang talked about her work and described the importance of the Women’s Health Initiative (WHI), from which she and her co-investigators pulled their data:

The Women’s Health Initiative was funded by the National Institutes of Health and American taxpayers’ dollars…  This was a huge investment of taxpayers’ dollars, and it has incredibly paid off, [producing] many published papers and, more importantly, many important messages and conclusions about the health of American women.

…

Women were enrolled [in the WHI] to reflect the multi-ethnic population of the U.S. So American Indians are represented, Mexican-American women are represented, black women are represented. You are never going to get the richness and diversity of the women represented in this database anywhere else in the world.

Previously: New research shows aspirin may cut melanoma risk

Researchers at Stanford have conducted the largest study ever examining new methods for preventing melanoma and found that women who took aspirin on a regular basis decreased their risk of developing the dangerous form of skin cancer.

The findings are significant because they have the potential to reduce the number of people diagnosed with melanoma, an estimated 76,600 for 2013, and to save lives. The skin cancer is projected to cause nearly 9,500 this year alone.

In the study, which was published today in the journal Cancer, researchers drew on data from the Women’s Health Initiative (WHI), which collected health information (including information on such things as aspirin and non-aspirin NSAIDs use) from postmenopausal U.S. women for an average of 12 years. As my colleague explains in a release:

The Stanford study focused on the data of roughly 60,000 Caucasian women who were selected because less skin pigment is a risk factor for melanoma. The Stanford researchers found that those who took aspirin decreased their risk of developing melanoma by an average of 21 percent. Moreover, the protective effect increased over time: There was an 11 percent risk reduction at one year, a 22 percent risk reduction between one and four years, and as much as a 30 percent risk reduction at five years and beyond.

…

One way aspirin may prevent melanomas is through its anti-inflammatory effects, [Jean Tang, MD, PhD, senior author of the study] said. Even though non-aspirin NSAIDs also reduce inflammation, they don’t use the same pathways that aspirin uses to become activated in the body. That difference may be the key to aspirin’s effectiveness.

The results are promising, but researchers caution that more studies need to be completed before they can definitively say “an aspirin a day will keep melanoma away.” Tang commented, “We don’t know how much aspirin should be taken, or for how long, to be most effective.”

Previously: New skin cancer target identified by Stanford researchers, How ultraviolet radiation changes the protective functions of human skin and Working to prevent melanoma
Photo by Andrew Ranta

Sparks flew at a symposium hosted by the Stanford Center for Health Research on Women & Sex Differences in Medicine, which I attended yesterday. One invited speaker -Louann Brizendine, MD, of the University of California at San Francisco – is the author of a couple of books titled The Male Brain and The Female Brain. Another invited speaker – neuroscientist Daphna Joel, PhD, who’d flown in from the University of Tel Aviv, in Israel – emphatically maintained that there is no such thing as a “male” brain or a “female” brain. “What we know,” she said bluntly, “is that males have brains and females have brains.”

Whatever the semantics of that debate, two things are pretty clear any way you slice it. First, male and female brains are mostly alike. Second, there are measurable and meaningful differences in what goes on inside male versus female brains. As another neuroscientist, UCLA’s Art Arnold, PhD, put it: “Every cell in a female’s brain expresses a set of genes that the cells in a male’s brain express at much lower levels, if at all.”

Adding heft to Arnold’s comment was a presentation by Nirao Shah, MD, PhD, of UCSF. The neuroanatomist showcased research in his lab that had pinpointed specific genes whose activity levels differed significantly in the brains of male and female mice. Many of these genes, he noted, have human analogs that have been implicated in alcoholism, autism, breast and prostate cancers, and more. By conducting rigorous experiments with mice in which one or another of such genes had been put out of commission, Shah and his colleagues were able to tease out the behavioral consequences of specific genes’ inactivation. For example, knocking out a particular gene in female mouse moms results in a massive dimunition in their willingness to defend their nests from intruders – a maternal mandate that normal female mice observe rigorously – yet has no other observable effect on their maternal or sexual behavior. Torpedoing a different gene radically reduces Minnie Mouse’s mating mood; but the Mickeys in which this gene has been trashed “are completely normal, as far as we can tell,” Shah said.

The upshot: Yes, there are significant differences in behavior (and therefore in brain action) and in gene activity in the brain cells of males and females. Those of male and female mice, that is. What about humans’?

Well, nobody was talking about knocking any genes out of people to see if the men indulge in fewer barroom brawls and the women start laughing off their babies’ cries of distress. But there are certainly some strong hints of medically significant differences: The ratio of men to women with autism run somewhere in the neighborhood of 8:1 or even 16:1. Depression is twice as common among women as among men – but only between menarche and menopause. Alzheimer’s disease abounds more in women, even after taking into consideration women’s greater longevity (itself a medically important difference), as does autoimmunity. On the other hand, Parkinson’s and schizophrenia preferentially affect men. There seems to be more at work here than the simple “absorption of gender stereotypes,” and it’s good to see hardcore biologists attacking the problem with all the scientific rigor at their disposal.

Let’s not call the whole thing off.

Previously: A call to advance research on women’s health issues
Photo by namuit

An article in the San Francisco Chronicle today discusses the need to include more females in scientific research and mentions efforts being taken at Stanford to fix the problem. Erin Allday writes:

…[T]here have been tremendous advances in studying women’s health issues and including women in drug trials and clinical studies. Most of those changes  followed a 1993 mandate by the  National Institutes of Health that women be included in  such studies.

But when it comes to basic science – studying the molecular mechanics of  diseases in cells and tissues and in mice and rats – almost all of the work is on subjects with the male XY chromosome pairing.

Stanford, at least, is aiming to dig into that problem with the creation of a  new center focused on sex and gender in health. The Stanford Center for Health Research on Women and Sex Differences in Medicine officially opens Wednesday with a conference on sex, gender and the brain, at which [Louann Brizendine], now a UCSF psychiatrist who has written two books on the male and female brain, is speaking.

“For just about everything in medical science, we’re still very male-focused,” said Marcia Stefanick, an obstetrics and gynecology professor at Stanford who is co-director of the new center. “Our basic understanding is missing a key ingredient, and that is the sex difference.”

Previously: Exploring sex differences in the brain and Women underrepresented in heart studies

Local readers, mark your calendar for a free, public event on the medical school campus on March 6. “seXX & seXY: A Dialogue on the Female Brain and the Male Brain,” will feature a variety of experts discussing sex differences in the brain and covering such topics as autism, Alzheimer’s disease and obesity. The event marks the launch of the Stanford Center for Health Research on Women and Sex Differences in Medicine, which will encourage scientists to study sex differences in cells, tissues, animal models and human health outcomes across the life span, with an emphasis on women’s health.

As I wrote in a story on the new endeavor:

The center will unite the many Stanford faculty members conducting health research on women and sex differences in basic biology and the influence of gender on disease. Some researchers, for example, are examining a risk factor for Alzheimer’s disease that may be seen in women only. Others are studying how to tailor diagnostic tests and treatments for women, as well as men, with cardiovascular disease. The center hopes to promote further research in all medical disciplines, as well as identify clinical areas (such as health issues in gay, lesbian and transgender people) that need to be recognized in order to provide health equity for everyone.

…

[Directors Marcia Stefanick, PhD, and Lynn Westphal, MD,] felt strongly that the center’s emphasis should not be solely on women, but also on their Y-chromosomed (and gender variant) counterparts. Women have better outcomes than men in many disease categories, but worse outcomes in others. Investigating why, for example, men have more all-cause cancers and more heart disease, and die at higher rates than women in every age category until age 80 and older, could be of clinical benefit to both sexes, they say, as will learning why women suffer more from autoimmune diseases and other illnesses.

“Understanding the reasons would shed light on diseases and allow us to tailor treatments,” said Westphal.

The March 6 symposium (for which people can register here) will be followed by a general women’s health forum on May 15; the events are designed to interest both a lay and professional audience.

Photo by Hey Paul Studios

Last week, I wrote about efforts to boost IUD use in developing countries. This form of birth control, despite its benefits, isn’t widely embraced here in the United States, either – with surveys showing that less than 10 percent of women of reproductive age use it. But, as reported earlier this week by Kaiser Health News, the recently enacted Affordable Care Act might change that:

IUDs and the hormonal implant — a matchstick-sized rod that is inserted under the skin of the arm that releases pregnancy-preventing hormones for up to three years — generally cost between $400 and $1,000. The steep upfront cost has deterred many women from trying them, women’s health advocates say, even though they are cost-effective in the long run compared with other methods, because they last far longer.

Under the Affordable Care Act, new plans or those that lose their grandfathered status are required to provide a range of preventive benefits, including birth control, without patient cost-sharing. Yet even when insurance is covering the cost of the device and insertion, some plans may require women to pick up related expenses, such as lab charges.

Long-acting reversible contraceptives (LARCs) require no effort once they’re put into place, so they can be an appealing birth-control option for teens and young women, whose rates of unintended pregnancy are highest, experts say.

Via Our Bodies, Our Blog
Previously: Promoting the use of IUDs in the developing world, For many women, no more co-pay for birth control and A look at the federal mandate to cover contraceptives

Estrogen-based hormone therapy has been a hotly debated issue for years. In 2002, the Women’s Health Initiative, the largest-ever federally sponsored study of postmenopausal women’s health, halted part of its trial examining hormone therapy. Published data showed that the combination of estrogen and progestin increased the risk for heart attacks, strokes, blood clots and breast cancer among postmenpausal women. It seemed certain to slam shut the door on hormone therapy for many women. Yet, a series of studies has softened that judgment. And now comes another.

As my colleague mentioned just yesterday, a new study from Stanford professor Natalie Rasgon, MD, PhD, and others has found that some women – specifically those who carry a gene that puts them at increased risk for developing Alzheimer’s – may benefit from an estrogen regimen. The word ”may” is a huge caveat here, as the study was small and certainly not definitive.

San Francisco Chronicle writer Erin Allday teased out the research in an article yesterday. And I spoke with Rasgon earlier in the week for a 1:2:1 podcast, as I was curious about yet another possible rebound for estrogen therapy. Rasgon reiterated to me that her study is far too small to be conclusive – “it opens more questions than it answers” - but it’s intriguing nonetheless.

Previously: Hormone therapy halts accelerated aging seen in women with Alzheimer’s genetic risk factor, Hormone therapy soon after menopause onset may reduce Alzheimer’s risk and Common genetic Alzheimer’s risk factor disrupts healthy older women’s brain function, but not men’s

Biological aging, as opposed to the chronological kind we celebrate or curse annually, is what makes us describe some people as “ageless” and others as “old beyond their years.” We are collections of cells, and what happens in the cell doesn’t stay in the cell. It  generates large-scale effects on our overall appearance, health and longevity.

A new study in JAMA indicates that otherwise healthy adults carrying a cellular signature of biological aging may be more vulnerable to infection and, once infected, more likely to exhibit symptoms. The experimenters first drew blood from 152 Pittsburgh residents, none of them over 55 years old, and dosed them with nose drops containing a common cold virus. Monitoring these volunteers for five days, the researchers took note of who sniffled and sneezed and who didn’t, and saw a correlation between study subjects’ susceptibility to the virus and a measure of biological aging called telomere shortening.

Telomeres, which cap the ends of each chromosome in every cell of all living creatures from fungi right on up to humans, are kind of like those plastic caps ringing each end of a shoelace. They stabilize chromosomes, keeping them from unraveling. (They prevent other damage, too.)

But telomeres aren’t so stable themselves. Rounds of cell division, bouts of stress, and episodes of inflammation cause them to shrink. If a telomere reaches a point where a chromosome’s integrity is challenged, the result could be cancer or some other malfunction in the cell housing the challenged chromosome.

Evolution has engineered protective mechanisms into cells so that if their telomeres get too short they die or, at least, lose their ability to divide any more. But this evolutionary emergency brake has its downside: It contributes to the slow but steady deterioration that manifests visibly in our aging skin and, less visibly, in all the other bodily organs.

In this case, the researchers were specifically interested in those bloodborne cells that comprise the immune system. But it’s widely believed that the state of telomeres in blood cells (the cells examined in the study) reflects their state in other tissues as well.

Just a week ago, a study in PLOS ONE led by Stanford psychopharmacologist Natalie Rasgon, MD, PhD, compared the telomeres in blood cells taken from high-functioning, well-educated, apparently fully healthy middle-aged women with a well-known genetic risk factor for late-onset Alzheimer’s disease (a good 15 percent of us are carriers) to those of otherwise matched non-carriers. The first group’s telomeres shortened by as much in two years as the second group’s did in ten, perhaps shedding some light on how this risk factor, called ApoE4, promotes cognitive decline. The good news was that the accelerated telomere shortening seen in ApoE4 carriers wasn’t observed  if they’d been on estrogen-based hormone therapy at the onset of menopause and stayed on it for the study’s  two-year duration.

While it might be nice to think longer telomeres are all it takes to ensure longevity, even the lengthiest telomeres are no match for a speeding truck. So be sure to look both ways before you cross the street.

Previously: Hormone therapy halts accelerated aging seen in women with Alzheimer’s genetic risk factor, Hormone therapy soon after menopause onset may reduce Alzheimer’s risk and Common genetic Alzheimer’s risk factor disrupts healthy older women’s brain function, but not men’s
Photo by ultrakickgirl