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Aging, Genetics, Men's Health, Neuroscience, Research, Stanford News, Women's Health

Having a copy of ApoE4 gene variant doubles Alzheimer’s risk for women but not for men

Having a copy of ApoE4 gene variant doubles Alzheimer's risk for women but not for men

brain cactus - smallSince the early 1990s, when Duke University neurologist Allen Roses, MD, first broke the news, it’s been known that a person carrying the gene variant known as ApoE4 is at elevated risk of getting Alzheimer’s disease. To this day ApoE4 is the strongest known single genetic risk factor for Alzheimer’s, a progressive neurological syndrome that robs its victims of their memory and reasoning ability.

But only now is it looking certain that the increased Alzheimer’s risk ApoE4 confers is largely restricted to women. Men’s fates don’t seem to be altered nearly as much by the genetic bad penny that is ApoE4, according to a new Annals of Neurology study led by Mike Greicius, MD, medical director of the Stanford Center for Memory Disorders.

Accessing two huge publicly available national databases, Greicius and his colleagues were able to amass medical records for some 8,000 people and show that initially healthy ApoE4-positive women were twice as likely to contract Alzheimer’s as their ApoE4-negative counterparts, while ApoE4-positive men’s risk for the syndrome was barely higher than that for ApoE-negative men.

What the heck is ApoE4 for, anyway? In my release on the new study, I wrote:

The ApoE gene is a recipe for a protein important for shuttling fatty substances throughout the body. This is particularly important in the central nervous system, as brain function depends on rapid rearrangement of such fatty substances along and among nerve cell membranes. The ApoE gene comes in three varieties — ApoE2, ApoE3 and ApoE4 — depending on inherited variations in the gene’s sequence. As result, the protein that the gene specifies also comes in three versions, whose structures and fatty-substance-shuttling performance differ. Most people carry two copies of the ApoE3 gene variant (one from each parent). But about one in five people carries at least one copy of ApoE4, and a small percentage have two ApoE4 copies. Numerous studies … have confirmed that ApoE4 is a key risk factor for Alzheimer’s disease, with a single copy of ApoE4 increasing that risk twofold or fourfold. Carrying two copies confers 10 times the risk of Alzheimer’s.

Early hints in the medical literature that the ApoE4 variant exerted differential effects on women’s versus men’s brains were largely ignored until now, says Greicius. He says that’s because most of the seminal ApoE4/Alzheimer’s genetics research was conducted as case-control studies: The ApoE4 gene version’s frequency in people with Alzheimer’s was compared to its frequency in people without the disease. (About half of those with Alzheimer’s, but only about 15 percent without it, are positive for ApoE4.)

But that method has limitations, says Greicius: “About 10-15 percent of ‘normal’ 70-year-olds will develop Alzheimer’s if you wait five or ten years.” Their lurking in the “normal” group dilutes the results. Moreover, Greicius says,“these kinds of genetic studies are looking for needles in a haystack, so they require large numbers of subjects – thousands – to achieve statistical significance. If you want to further examine male/female differences, you have to double the sample size.” That’s costly.

And that’s how come the large government- and industry-supported repositories to which Greicius and his team resorted are such a great idea.

Previously: Estradiol – but not Premarin – prevents neurodegeneration in women at heightened dementia risk, Common genetic Alzheimer’s risk factor disrupts healthy older women’s brain function, but not men’s, Hormone therapy halts accelerated biological aging seen in women with Alzheimer’s genetic risk factor and A one-minute mind-reading machine? Brain-scan results distinguish mental states
Photo by Sean Michael Ragan

Global Health, Pediatrics, Public Safety, Research, Stanford News, Women's Health

Empowerment training prevents rape of Kenyan girls

Empowerment training prevents rape of Kenyan girls

Adolescent girls in the slums of Nairobi, Kenya, are frequent targets of sexual harassment and assault: Nearly one in five of them is raped each year. When these crimes are perpetrated against Nairobi’s teen girls, they’re often expected to react with shame and silence.

But a small non-governmental organization, No Means No Worldwide, has a strategy to change that. The co-founders, Jake Sinclair, MD, and Lee Paiva, an American husband-and-wife team, developed a curriculum of empowerment training to teach girls that it’s OK to say “no” to unwanted sexual advances. The training also gives girls specific verbal and physical skills to defend themselves, as well as information about where to go for help after a rape or other sexual assault.

The results are impressive. Stanford researchers who work with Sinclair and Paiva report today in Pediatrics that the empowerment training cut annual rates of rape by more than a third. Among the group of 1,978 girls trained during the study, more than half used their new knowledge to fend off attempted rape, and 65 percent stopped instances of harassment, halting hundreds of incidents.

From our press release about the research:

“Clearly, girls should never be placed in these situations in the first place,” said Clea Sarnquist, DrPH, the study’s lead author and a senior research scholar in pediatrics at Stanford. Changing males’ attitudes and behavior about assault is an important area for the team’s current and future work, she said. “But with such a high prevalence of rape, these girls need something to protect them now. By giving them the tools to speak up and the knowledge that ‘I have domain over my own body,’ we’re giving them the opportunity to protect themselves.”

The video above, one of a series of testimonials that No Means No Worldwide has collected from Nairobi girls, shows the power of that sense of domain over one’s body. In the video, a schoolgirl named Catherine tells how she stopped a male student from harassing her. When the video begins, it’s impossible not to notice how young and vulnerable she seems. But then she recounts how, when this boy followed her and demanded sex, she remembered her self-defense classes.

“I stood and maintained eye contact,” she says in the video. “I warned him that day and told him he should never in his life dare follow me.”

As she says the words, her demeanor transforms: She draws herself up straight, looks directly in the camera, and raises her index finger in a gesture of commanding attention.

Maryanne Wangui, a young Kenyan woman who recorded many of the testimonials, said something to me that resonates with Catherine’s account and sticks in my mind: “If you give girls the right skills, they know what to do. It doesn’t matter the age of the girl or the size of the girl; they’re all powerful inside.”

Previously: Self-defense training reduces rapes in Kenya
Video courtesy of No Means No Worldwide

Ethics, In the News, Sports, Stanford News, Women's Health

Arguing against sex testing in athletes

Arguing against sex testing in athletes

Testosterone does not a man – nor a woman – make. So argues Stanford medical anthropologist Katrina Karkazis, PhD, in a New York Times op-ed today. She cites evidence against the scientific and ethical soundness of sex-testing policies used since 2011 by sports governing organizations including the International Olympic Committee, the Fédération Internationale de Football Association and the International Association of Athletics Federations.

From the piece:

Rather than trying to decide whether an athlete is “really” female, as decades of mandatory sex tests did, the current policy targets women whose bodies produce more testosterone than is typical. If a female athlete’s T level is deemed too high, a medical team selected by the sport’s governing bodies develops a “therapeutic proposal.” This involves either surgery or drugs to lower the hormone level. If doctors can lower the athlete’s testosterone to what the governing bodies consider an appropriate level, she may return to competition. If she refuses to cooperate with the investigation or the medical procedures, she is placed under a permanent ban from elite women’s sports.

Sports authorities argue that screening for high T levels is needed to keep women’s athletics fair, reasoning that testosterone improves performance. Elite male athletes generally outperform women, and this difference has been attributed to men’s higher testosterone levels. Ergo, women with naturally high testosterone are thought to have an unfair advantage over other women.

But these assumptions do not match the science. A new study in Clinical Endocrinology fits with other emerging research on the relationship between natural testosterone and performance, especially in elite athletes, which shows that T levels can’t predict who will run faster, lift more weight or fight harder to win. The study, of a sample of 693 elite athletes, revealed a significant overlap in testosterone levels among men and women: 16.5 percent of the elite male athletes had testosterone in the so-called female range; nearly 14 percent of the women were above the “female” range.

Karkazis concludes, “Barring female athletes with high testosterone levels from competition is a solution to a problem that doesn’t exist. Worse, it is pushing young women into a choice they shouldn’t have to make: either to accept medically unnecessary interventions with harmful side effects or to give up their future in sports.”

Previously: Is the International Olympic Committee’s policy governing sex verification fair?, Researchers challenge proposed testosterone testing in select female Olympic athletes and Gender ambiguity gets attention

Behavioral Science, Nutrition, Obesity, Research, Women's Health

Obesity and smoking together may decrease taste of fat and sweet but increase consumption

puddingA study from Washington University School of Medicine in St. Louis and Philadelphia’s Monell Center has found that obese women who smoke cigarettes may have reduced sensitivity to the tastes of sweetness and fat in food and may be more likely to eat more calories.

Researchers engaged 47 female participants ages 21 to 41, grouped as follows: obese smokers, obese nonsmokers, normal-weight smokers, and normal-weight nonsmokers. All of the participants tasted vanilla puddings and were asked to rate the sweetness and creaminess of each one. The researchers found that the women who were obese and smokers rated less creaminess and sweetness in the puddings than the other three groups did.

From a release:

[Study author Yanina Pepino, PhD,] cautioned that the study only identified associations between smoking and taste rather than definitive reasons why obese smokers were less likely to detect fat and sweetness. But the findings imply that the ability to perceive fat and sweetness — and to derive pleasure from food — is compromised in female smokers who are obese, which could contribute to the consumption of more calories.

“Obese people often crave high-fat foods,” she said. “Our findings suggest that having this intense craving but not perceiving fat and sweetness in food may lead these women to eat more. Since smoking and obesity are risk factors for cardiovascular and metabolic diseases, the additional burden of craving more fats and sugars, while not fully tasting them, could be detrimental to health.”

The results were published in the journal Obesity.

Previously: Obesity is a disease – so now what?How eating motivated by pleasure affects the brain’s reward system and may fuel obesity and The brain’s control tower for pleasure
Photo by dutchfulthinking.blogspot.com

Global Health, HIV/AIDS, Women's Health

Preventing domestic violence and HIV in Uganda

Preventing domestic violence and HIV in Uganda

Ugandan dancers - 560

The woman was terrified, as she had just come from the hospital, where she discovered she was HIV-positive. It wasn’t so much the virus she feared, as the reaction from her husband. If he were to find out, he would surely beat her and throw her out of the house.

As predicted, the husband arrived home and seeing his wife in distress, forced her to confess what she had learned. “Either I cut you in two pieces and throw you in the ditch or leave the house,” he yelled, his arm raised in threat.

Fortunately, the wife wasn’t harmed, for the drama was merely that – a work of street theatre designed to break the traditional patterns of domestic violence and HIV in Uganda. The drama is one of the creative strategies being used by the nonprofit Center for Domestic Violence Prevention in Kampala, Uganda to effectively reduce incidents of domestic violence by more than 50 percent in the communities it serves.

In the process, group also aims to reduce the incidence of HIV, which affects 7.2 percent of adults in the East African nation, according to the latest figures from the United Nations Joint Programme on HIV/AIDS.

The organization works by mobilizing local men and women and training them in various interventions, like the street drama, address pervasive problem of violence among intimate partners. According to its figures, 59 percent of women between the ages of 15 and 49 say they have experienced physical or sexual violence by a husband or partner at some point in their lives.

“We are talking about an epidemic,” said Tina Musuya, a social worker and a women’s rights activist who directs the organization.

I was fortunate to see the street theatre program in action during a recent trip to Uganda with the American Jewish World Service, an international development organization that works to end poverty and promote human rights in the developing world. Fifteen of us, all Global Justice Fellows with the organization, visited CEDOVIP’s offices in Kampala and then fanned out to see the group’s work in action in the streets of Kampala one sunny afternoon.

A crowd had already begun to materialize by the time we arrived in one of the city’s poor neighborhoods, where three drummers had lured people from their homes with a lively beat. Two female dancers in colorful red outfits (pictured above) then entertained the crowd, whose curiosity was heightened by the presence of us five white foreigners. By the time the drama began, more than 100 people had gathered in the dirt road – youngsters who tugged at our hands, older women who sat on wooden stools to watch and groups of men who stood on the sidelines, quietly assessing the unfolding drama.

The story begins when the woman returns from the hospital to cry on a neighbor’s shoulder. The husband then arrives and suspects something is up. He falls into a rage on learning the wife’s news, threatening to “break her bones” and ordering her to leave the house. But the wife says she has nowhere to go. Besides, she tells him, she acquired the virus from him.

A narrator, dressed in an orange shirt, periodically freezes the drama, soliciting suggestions from the crowd on what the couple should do. One observer tells the woman to call the police. Another urges bystanders to intervene to help save the situation.

“We have so many instances of violence in our neighborhood,” the narrator concludes, speaking in Luganda while our host translates. “See what happens in violent situations when the woman becomes HIV-positive. Be supportive. Support the victims, but also support the man. Change the behavior. Break the silence.”

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Cancer, Global Health, Stanford News, Women's Health

Stanford fellow addresses burden of cervical cancer in Mongolia

Stanford fellow addresses burden of cervical cancer in Mongolia

Mongolian clinic - smallCervical cancer is the third most common cancer among women worldwide, and Mongolia has one of the highest incidence rates in Eastern Asia. Prevention and early detection programs are essential to counteract its prevalence, especially in developing countries.

However, women encounter barriers to knowledge and access to cervical cancer screening services in Mongolia – a country with low population density. The urban–rural divide, lagging healthcare reform, and cultural differences are cited as core factors leading to lack of awareness and treatment.

To address the rising burden, a national cervical cancer screening program was implemented in August 2012 by Mongolia’s Ministry of Health (MOH) facilitated by a grant from the Millennium Challenge Corporation.

Gendengarjaa Baigalimaa, MD, the 2013-14 Developing Asia Health Policy Fellow at Stanford’s Walter H. Shorenstein Asia-Pacific Research Center in the Freeman Spogli Institute, has been evaluating the effects of that program. She serves as a gynecological oncologist at the Mongolian National Cancer Center (NCC). Her early findings show that awareness of cervical cancer has increased, and more women and girls are now getting screened. Gendengarjaa recently talked about her research.

What does your “typical” patient look like at the NCC and how has your work informed your research?

Patients typically arrive at the NCC with an advanced stage of disease – 70 percent of these women have progressive forms of cervical cancer. Of course it is not easy to work with patients who are this far along, especially if we are unable to offer full palliative services. As the only cancer center in the nation, just 10 gynecological oncologists are available to take on the high demand for treatment services. Healthcare providers and policymakers designed the Mongolian Cervical Cancer Program to address the alarming incidence rate. My research analyzes behavioral change before and after the introduction of the national screening program, bearing in mind my experiences with my own patients.

What does the national cervical cancer screening program facilitate?

Before the program was implemented, regular cervical cancer screening did not exist in Mongolia. The program diffused and strengthened primary care screening services (Pap test) as well as prevention programs. Gynecological doctors from the NCC were systematically dispatched to the 338 soums or districts throughout the nation. They trained local doctors and midwives on how to administer the Pap test. The program coordinated two initiatives: a pilot HPV vaccination program for girls aged 11-15 years from four select areas and a Pap test program for women aged 30-60 years. The women and girls who participated are urged to get screened every three years thereafter. Health education campaigns were also broadcast on select television and radio programs targeted at women and girls.

Comparing a survey taken at the program’s outset in 2010 to your survey at the program’s conclusion in 2013, what behavioral changes have been observed?

Our preliminary results have shown increased knowledge about risk factors and screening services. Women in both rural and urban areas are now more informed about cervical cancer risk factors. Awareness of the need for a Pap test increased from 15.3 percent in 2010 to 45.3 percent in 2013. The respondents also reported being more educated about the suggested frequency of visiting a doctor, and the availability of services outside of Ulaanbaatar. Due to increased knowledge, 54.2 percent of the women surveyed confirmed that they had attended cervical screening services.

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Cardiovascular Medicine, Women's Health

Study shows many women have a limited knowledge of stroke warning signs

Study shows many women have a limited knowledge of stroke warning signs

woman_heartMore than 795,000 people in the United States have a stroke each year, and about 60 percent of stroke deaths occur in women. But despite this, and the fact that stroke affects more women than men, a new survey conducted by the American Heart Association/American Stroke Association shows that women are largely unfamiliar with the warning signs of stroke. Study researchers said the findings, which are based on a 2012 phone survey of 1,205 women in the United States, are a “significant barrier to reducing death and disability related to stroke.”

According to a release, findings included:

  • More than half (51 percent) of the women identified sudden weakness or numbness on one side of the face, arms or legs as a warning sign of a stroke.
  • Less than half (44 percent) identified difficulty speaking or garbled speech as a warning sign.

Less than a fourth identified other signs of a stroke, including:

  • sudden severe headache (23 percent);
  • unexplained dizziness (20 percent); and
  • sudden vision loss (18 percent).

The associations have developed the acronym F.A.S.T. to help people identify and respond to signs of stroke. It stands for face drooping. arm weakness, speech difficulty and time to call 9-1-1.

Previously: Heart attacks and chest pain: Understanding the signs in young women, Are young adults in denial about how lifestyle choices affect their health? and Gap exists in women’s knowledge of heart disease
Photo by Nicola Jones

Global Health, Sexual Health, Women's Health

Sex work in Uganda: Risky business

Sex work in Uganda: Risky business

We step across a sewage channel to enter an unmarked, tin-roof building, leaving the bright sunlight for the dark corridors of a 23-room inn in a busy commercial district in Kampala, Uganda. More than a dozen women huddle on the mud floor in a small rectangular courtyard whose walls are charcoal-black. We gradually come to realize that we’ve arrived at a brothel, the destination for our field tour with the Women’s Organization Network for Human Rights Advocacy, a prominent group that fights for the rights of Uganda’s sex workers.

One woman in her 30s, dressed in a black head scarf, does much of the talking for the women at the brothel, speaking in her native Luganda while the manager of the inn translates. The woman says she lost her husband and had no source of income to support herself and her children. “I almost committed suicide,” she says, but a friend encouraged her to try sex work to earn money. “My friend said, ‘I will show you what to do.’” Behind her, three wooden doors lead to squalid, closet-sized rooms where the women live and work their trade.

The women, we learn, have turned to sex work as a matter of survival. Many have lost husbands or partners on whom they depended for income, and they lack the education or skills to find other jobs that pay a livable wage.

“If they turn away from sex work, how will they feed their children or pay their school fees?” one WONETHA official says.

But the work comes with a price. The women frequently face client abuse, beatings and harassment on the streets, even police brutality – including rape, beatings and extortion – and the ever-present risk of HIV.

“Sex workers are facing a health and human rights crisis in Uganda. Despite this, little is being done to protect the most basic human rights of sex workers,” declares a pink banner at WONETHA’s headquarters in central Kampala.

The largest organization of its kind in East Africa, the group works to provide the women with better access to medical care, legal and social services, job training and freedom from violence and arbitrary arrests.

I met with members of the nonprofit group in February as a Global Justice Fellow with American Jewish World Service, an international development organization that aims to end poverty and promote human rights in the developing world. I was among 15 fellows from the Bay Area who spent nine days in Uganda learning about the work of human rights organizations that advocate for women, girls and the LGBT community.

One of WONETHA’s goals is helping prevent HIV among the sex workers and obtain access to medical care for those who are infected with the virus. Sex workers are the greatest at-risk group in the country, with an infection rate of 37 percent in 2010, according to the Uganda AIDS Commission.  At the national level, Uganda was particularly hard-hit by AIDS early on, with the disease reaching epidemic proportions in the 1980s. Between 1992 and 2000, however, there was a dramatic decline in incidence – from an estimated high of about 18.5 percent to 5 percent. In recent years, the number of infections has begun to rise again in what many see as a disturbing trend; the infection rate reached 7.2 percent in 2012, according to the United Nations Joint Programme on HIV/AIDS.  Lax attitudes regarding safe sex and a lack of condom use are among the factors cited in the trend.

WONETHA distributes condoms to help protect sex workers against HIV and other sexually transmitted diseases. A dozen large boxes of Chinese-made condoms, supplied by the United Nations Population Fund, occupied a cool space in the group’s headquarters on the day of our visit – some 100,000 of them ready to be distributed to various locations around town.

But condom use, we are told, is not always guaranteed. Clients may resist using them or pay more for a condom-free encounter. A program manager with the group told me that even in marriages, many men resist use of condoms but continue to have multiple partners – putting their wives and the other partners at risk.

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Clinical Trials, Imaging, Neuroscience, Research, Stanford News, Women's Health

Estradiol – but not Premarin – prevents neurodegeneration in women at heightened dementia risk

Estradiol - but not Premarin - prevents neurodegeneration in women at heightened dementia risk

bottle of pillsWomen near the age of menopause and at elevated risk for dementia – owing, say, to a family history of Alzheimer’s disease, a personal history of major depression, or a genotype positive for the infamous Alzheimer’s-predisposing gene variant, ApoE4 – may want to consider talking to their doctor about estrogen-based hormone therapy.

In a brain-imaging study just published in PLOS ONE, hormone therapy protected key “early warning” brain regions from metabolic decline in women who fit that description – but only if they started therapy shortly after reaching menopause, and only if the pill they took contained just estradiol, the dominant female sex-steroid hormone. Premarin, a more widely used hormone-therapy formulation derived from the urine of pregnant mares, was far less protective.

Premarin contains more than 30 substances, with estradiol accounting for only about 17 percent. Other components exert various endocrinological effects on different tissues. In my release on the new study, I wrote:

More than 20 million women in the United States are between 45 and 55 years old – an age range at which many once were considered prime candidates for Premarin. Hormone therapy… was… widely heralded as protecting postmenopausal women from heart disease, osteoporosis and even cognitive decline.

Indeed, from 1992 through 2001 Premarin was the most widely prescribed drug in the United States. Then came the deluge. Here’s the backstory:

In July 2002, a large multicenter study of hormone therapy’s effects was abruptly halted when – contrary to expectations – woman assigned to PremPro (Premarin plus progestin, a synthetic version of progesterone, another important female steroid hormone) developed more cardiovascular disease than those getting a placebo. Within 18 months, about half of American women who’d been on hormone therapy abandoned it. Its use has since plunged considerably further.

Then in 2003, an ancillary study called WHIMS (“Women’s Health Initiative Memory Study”) reported that dementia incidence among 65- to 79-year-old women randomly assigned to PremPro was double  that of women on placebo. This disappointing finding was widely covered in the media.

But Rasgon and her colleagues’ findings are consistent with other analyses indicating that women initiating hormone therapy within five years of their last menstrual cycle experienced beneficial brain effects. In fact, major differences in trial design may explain the discrepancy between WHIMS’s decidedly negative results and the new study’s more nuanced ones.

The WHIMS women were older, on average, than those in Rasgon’s study and were beginning hormone therapy after a long hiatus during which their bodies were no longer producing substantial quantities of estrodiol. Moreover, the PremPro given to women in the active arms of WHIMS contained progestin – which, the new study shows, speeds metabolic deterioration in at least dementia-prone women’s brains.

Natalie Rasgon, MD, PhD, director of the Stanford Center for Neuroscience in Women’s Health and the study’s lead author, puts it plainly. “Hormone therapy’s neurological effect on women at risk for dementia depends critically on when they begin therapy and on whether they use estradiol or Premarin.”

Previously: Hormone therapy halts accelerated biological aging seen in women with Alzheimer’s genetic risk factor, Hormone therapy soon after menopause onset may reduce Alzheimer’s risk and Study shows common genetic risk factor for Alzheimer’s disrupts brain function in healthy older women, but not men
Photo by Canned Muffins

Cancer, NIH, Public Health, Women's Health

Study shows daily aspirin could lower women’s risk of ovarian cancer

Study shows daily aspirin could lower women's risk of ovarian cancer

aspirinA team of researchers at the National Cancer Institute have conducted the largest study to date assessing the relationship between non-steroidal anti-inflammatory drugs and ovarian cancer risk. Their findings show that taking aspirin daily may lower women’s risk of ovarian cancer; however researchers caution that more studies are needed before clinical recommendations can be made.

In the study, researchers examined a dozen previous epidemiological studies that included roughly 8,000 women diagnosed with ovarian cancer and nearly 12,000 women who did not have the disease. According to an NCI release:

The researchers determined that participants who reported daily aspirin use had a 20 percent lower risk of ovarian cancer than those who used aspirin less than once per week. For non-aspirin NSAIDs (non-steroidal anti-inflammatory drugs), which include a wide variety of drugs, the picture was less clear: the scientists observed a 10 percent lower ovarian cancer risk among women who used NSAIDs at least once per week compared with those who used NSAIDs less frequently. However, this finding did not fall in a range that was significant statistically. In contrast to the findings for aspirin and NSAIDs, use of acetaminophen, which is not an anti-inflammatory agent, was not associated with reduced ovarian cancer risk.

This study comes on the heels of Stanford research showing that aspirin use appears to cut the risk of another type of cancer (melanoma) in women.

Previously: Can repackaging aspirin get more people to take it daily for prevention? and New research shows aspirin may cut melanoma risk
Photo by Chaval Brasil

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