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Health Disparities, Men's Health, Public Health, Research, Stanford News, Women's Health

Why it’s critical to study the impact of gender differences on diseases and treatments

man_womanWhen it comes to diagnosing disease and choosing a course of treatment, gender is a significant factor. In a Stanford BeWell Q&A, Marcia Stefanick, PhD, a professor of medicine at the Stanford Prevention Research Center and co-director of the Stanford Women & Sex Differences in Medicine Center, discusses why gender medicine research benefits both sexes and why physicians need to do a better job of taking sex difference into consideration when make medical decisions.

Below Stefanick explains why a lack of understanding about the different clinical manifestations of prevalent diseases in women and men can lead to health disparities:

…Because we may have primarily studied a particular disease in only one of the sexes, usually males (and most basic research is done in male rodents), the resulting treatments are most often based on that one sex’s physiology. Such treatments in the other sex might not be appropriate. One example is sleep medication. Ambien is the prescription medicine recently featured on the TV show, 60 Minutes. Reporters found out that women were getting twice the dose they should because they had been given the men’s doses; consequently, the women were falling asleep at the wheel and having accidents. Physicians had not taken into account that women are smaller and their livers’ metabolize drugs differently than do men’s. Some women have responded by reducing their own medication dosages, and yet that practice of self-adjusting is not the safest way to proceed, either.

Previously: A call to advance research on women’s health issues, Exploring sex differences in the brain and Women underrepresented in heart studies
Photo by Mary Anne Enriquez

Fertility, Health and Fitness, Men's Health, Public Health, Research, Stanford News

Poor semen quality linked to heightened mortality rate in men

Poor semen quality linked to heightened mortality rate in men

sperm graffitiMen with multiple defects in their semen appear to be at increased risk of dying sooner than men with normal semen, according to a study of some  12,000 men who were evaluated at two different centers specializing in male-infertility problems.

In that study, led by Michael Eisenberg, MD, PhD, Stanford’s director of male reproductive medicine and surgery, men with more than one such defect such as reduced total semen volume, low sperm counts or motility, or aberrant sperm shape were more than twice as likely to die, over a seven-and-a-half-year follow-up period, than men found to be free of such issues.

Given that one in seven couples in developed countries encounter fertility problems at some point, Eisenberg told me, a two-fold increase in mortality rates qualifies as a serious health issue. As he told me for an explanatory release I wrote about the study:

“Smoking and diabetes — either of which doubles mortality risk — both get a lot of attention… But here we’re seeing the same doubled risk with male infertility, which is relatively understudied.”

Moreover, the difference was statistically significant, despite the fact that relatively few men died, due primarily to their relative youth (typically between 30 and 40 years old) when first evaluated. And the difference persisted despite the researchers’ efforts to control for differences in health status and age between the two groups.

Eisenberg has previously found that childless men are at heightened risk of death from cardiovascular disease and that men with low sperm production face increased cancer risk.

Previously:  Men with kids are at lower risk of dying from cardiovascular disease than their childless counterparts and Low sperm count can mean increased cancer risk
Photo by Grace Hebert

Fertility, Men's Health, Research, Stanford News

Researchers create primordial germ cells from stem cells of infertile men

Researchers create primordial germ cells from stem cells of infertile men

New research from Stanford and Montana State University shows that stem cells made from the skin of adult, infertile men can be used to create primordial germ cells, which are cells that normally become sperm, when transplanted into the reproductive system of mice.

The findings hold the potential to shed light on the earliest steps of human reproduction and could lead to the development of future therapies for men diagnosed with azoospermia, the most severe form of male factor infertility, or those rendered sterile after cancer treatments. My colleague Krista Conger explains the work in a release:

The research used skin samples from five men to create what are known as induced pluripotent stem cells, which closely resemble embryonic stem cells in their ability to become nearly any tissue in the body. Three of the men carried a type of mutation on their Y chromosome known to prevent the production of sperm; the other two were fertile.

The germ cells made from stem cells stopped differentiating in the mice before they produced mature sperm (likely because of the significant differences between the reproductive processes of humans and mice) regardless of the fertility status of the men from whom they were derived. However, the fact that the infertile men’s cells could give rise to germ cells at all was a surprise.

Previous research in mice with a similar type of infertility found that although they had germ cells as newborns, these germ cells were quickly depleted. The Stanford findings suggest that the infertile men may have had at least a few functioning germ cells as newborns or infants. Although more research needs to be done, collecting and freezing some of this tissue from young boys known to have this type of infertility mutation may give them the option to have their own children later in life, the researchers said.

The findings were published today in Cell Reports.

Previously: Stanford researchers work to increase the odds of in vitro fertilization success and New York Times shows how Stanford researchers solved the “egg maturation puzzle”

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 a 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

Cardiovascular Medicine, Genetics, Health and Fitness, Men's Health, Stanford News

The ultramarathoner’s heart

The ultramarathoner's heart

Nuttall-trail 2-webThe manufacturer’s warranty on the human heart is about 100 years or 2.5 billion beats. But do ultra-long-distance runners void this warranty when they regularly run races of 50 to 100 miles?

This was the question at the top of my mind as I wrote a tall tale about Mike Nuttall, a visionary Silicon Valley product designer and an ultramarathoner with hereditary heart disease, featured in the cardiovascular health issue of Stanford Medicine. In 2010 he had a heart attack and a triple bypass operation. Then he went on to run one of the most challenging races on the planet.

Was this fearlessness or folly?

An ultramarathoner pushes a body to its outer limits. Bones and joints are pounded. Dehydration can upset the electrolyte system, the delicate balance of salts and fluids that regulates heart, nerve and muscle functions. The heart, the ultramarathoner of organs, goes into overdrive for about 24 hours. But above all, an ultramarathon tests the mind, as a runner strives to override the brain’s overwhelming signals of pain and fatigue.

In the story, there are plenty of opinions from friends and heart experts on the wisdom of Nuttall’s post-heart-attack decision. But I guess, in the end, what he did was personal and heartfelt.

Previously: Study reveals initial findings on health of most extreme runners, Euan Ashley, MD, on personalized medicine for heart disease and Mysteries of the heart: Stanford Medicine magazine answers cardiovascular questions
Photo by Bert Keely (Nuttall’s wingman)

In the News, Infectious Disease, Men's Health, Public Safety, Research, Stanford News

Exploring how gender affects the immune system

Exploring how gender affects the immune system

man_coldA piece published today on Slate examines how sex hormones, like estrogen and testosterone, may impact the strength of men and women’s immune systems. As noted in the article, recent research from Stanford immunologist Mark Davis, PhD, who directs Stanford’s Institute for Immunity, Transplantation and Infection, and his colleagues offers new insights on the issue:

… it’s been difficult to establish any direct link between levels of sex hormones circulating in the blood and the performance of men’s and women’s immune systems.

Recent research is now beginning to firmly establish that link. This month, a team of scientists at Stanford University has reported some of the best evidence yet that testosterone directly influences immune system function in men. The researchers took blood samples from male and female volunteers who were given a flu shot. Women had higher levels of immune system molecules circulating in their blood than men, and they produced more effective antibodies against the flu virus. And there were not only differences between men and women, but there were differences among men—the men with the weakest response to the flu shot had high levels of both testosterone and testosterone-induced enzymes, suggesting that high levels of testosterone can suppress immunity.

This finding that testosterone may dial down the immune system in humans is consistent with the results of studies of other animals, ranging from fish to chimps.

For more details on the study and why high testosterone may provide a less obvious evolutionary advantage, read this December Scope post from my colleague Bruce Goldman.

Previously: In men, a high testosterone count can mean a low immune responseAdults’ immune systems “remember” microscopic monsters they’ve seen beforeImmunology escapes from the mouse trap and Immunology meets infotech
Photo by Iain Farrell

Aging, Chronic Disease, Health and Fitness, Men's Health, Research, Women's Health

More evidence that prolonged inactivity may shorten life span, increase risk of chronic disease

More evidence that prolonged inactivity may shorten life span, increase risk of chronic disease

sitting_deskIf you have a lengthy daily commute, spend hours at a desk clacking on the computer, or sit for a prolonged period for other reasons, a pair of recent studies may have you leaping to your feet.

The first study, conducted by researchers at Cornell University, examined the effects of sitting for a long period of time each day over a 12-year period. Results showed that individuals who were inactive for more than 11 hours had a 12 percent higher mortality rate than those who sat for four hours or less. And don’t think you’re not at risk because you occasionally hit the gym. Cornell researcher Rebecca Seguin, PhD, explained in a Futurity post:

The assumption has been that if you’re fit and physically active, that will protect you, even if you spend a huge amount of time sitting each day… In fact, in doing so you are far less protected from negative health effects of being sedentary than you realize.

While this study focused on postmenopausal women, additional research from Kansas State University shows that the health risks of being sedentary affect both both genders. The study analyzed data on nearly 200,000 men and women ages 45 to 106 taken from a large Australian study of health and aging. The research showed that both exercising and reducing sitting time were key to improving health. MedicalXPress reports:

Even standing throughout the day—instead of sitting for hours at a time—can improve  and quality of life while reducing the risk for  such as , diabetes, heart disease, stroke, breast cancer and colon cancer, among others.

Sitting for prolonged periods of time—with little muscular contraction occurring—shuts off a molecule called lipoprotein lipase, or LPL, [Sara Rosenkranz, PhD,] said. Lipoprotein lipase helps to take in fat or triglycerides and use it for energy.

“We’re basically telling our bodies to shut down the processes that help to stimulate metabolism throughout the day and that is not good,”  [Rosenkranz] said. “Just by breaking up your , we can actually upregulate that process in the body.”

Previously: Exercise is valuable in preventing sedentary deathIs standing healthier than sitting?How sedentary behavior affects your health and Stanford hosts conference on the science of sedentary behavior 
Photo by Danny Choo

Evolution, Immunology, Infectious Disease, Men's Health, Research, Stanford News

In men, a high testosterone count can mean a low immune response

In men, a high testosterone count can mean a low immune response

alpha maleMen have deeper voices and tons more facial and body hair than women. They are (usually) bigger, stronger, and much more likely to risk their lives on a whim. I, for example, have been known to bite a full-sized salami in half with a single snap of my jaws when hungry, angry or threatened. Or just for the hell of it.

But when it comes to immune response, men are wimps. It’s well documented that, for reasons that aren’t clear, men are more susceptible to bacterial, viral, fungal and parasitic infection than women are and that men’s immune systems don’t respond as strongly as women’s to vaccinations against influenza, yellow fever, measles, hepatitis and many other infectious diseases.

A new study just published in the Proceedings of the National Academy of Sciences by immunologist Mark Davis, PhD, who directs Stanford’s Institute for Immunity, Transplantation and Infection, and his colleagues may explain why. The same steroid hormone that makes a man’s beard, bones and muscles grow operates – albeit it in a slightly indirect way – to shrink immune responsiveness. Yep, we’re talking about (sigh…) that much-maligned male molecule, testosterone. In a nutshell, high circulating testosterone levels boost the activity of a clutch of genes that, among other things, dial down the aggressiveness with which our immune systems fight back against invading pathogens.

Now why, we ask ourselves, would evolution be so perverse as to have designed a hormone that on the one hand enhances classic male secondary sexual characteristics such as muscle strength, beard growth (or antler size, as the case may be) and risk-taking propensity – the very hallmarks of the alpha male – but on the other hand wussifies men’s immune systems?

Here’s what I got from talking at length (and, I admit, in an uncharacteristically high-pitched voice) to Davis in preparation for the news release I wrote about the study:

The evolutionary selection pressure for male characteristics ranging from peacocks’ plumage to deer’s antlers to fighter pilots’ heroism is pretty obvious: Females, especially at mating-cycle peaks, prefer males with prodigious testosterone-driven traits. Davis speculates that high testosterone may provide another, less obvious evolutionary advantage… Men are prone to suffer wounds from their competitive encounters, not to mention from their traditional roles in hunting, defending kin and hauling things around, increasing their infection risk. While it’s good to have a decent immune response to pathogens, an overreaction to them — as occurs in highly virulent influenza strains, SARS, dengue and many other diseases — can be more damaging than the pathogen itself. Women, with their robust immune responses, are twice as susceptible as men to death from the systemic inflammatory overdrive called sepsis. So perhaps, Davis suggests, having a somewhat weakened (but not too weak) immune system can prove more lifesaving than life-threatening for a dominant male in the prime of life.

Previously: Best thing since sliced bread? A (potential) new diagnostic for celiac disease, Deja Vu: Adults’ immune systems “remember” microscopic monsters they’ve seen before, Immunology escapes from the mouse trap and Immunology meets infotech
Photo by Craig Sunter *Click-64*

Men's Health, Women's Health

Living with disorders of sex development

A touching story in Pacific Standard about people born as intersex individuals caught my attention today. Writer Alice Dreger begins by quoting a note she received from a man named Jim; he wrote to her about a community resource Dreger helped establish that he says “basically saved my life.” Jim was born with androgen insensitivity syndrome.

Dreger writes:

I offered to meet the next morning at the local tea place. And then I started wondering, as I often do with these out-of-the-blue communiqués, if this message was a fake. Was I being set up?

But the minute I saw Jim, I knew he was real. I knew he was real because he started crying, and couldn’t talk. It was a reaction I’d seen before among people with disorders of sex development (DSD) who had been too closeted to meet another person with their condition, but who could get up the gumption to ask to meet me. I served as a way out of the closet, and so I represented the first human they came upon when they opened the door. I always tried, in my reaction, to signal simply, “Yes, you are a fellow human, and I am glad you are here.” I always have trouble not crying myself.

Previously: Is the International Olympic Committee’s policy governing sex verification fair?Researchers challenge proposed testosterone testing in select female Olympic athletes and Bay Area’s first DSD parent support group meets this week 
Related: Stanford author explores struggles of intersex individuals, their families and doctors and Karkazis on intersex people
Via @edyong209

Aging, Cancer, Complementary Medicine, Men's Health

Practicing Qigong may help older prostate cancer survivors fight fatigue, pilot study finds

Practicing Qigong may help older prostate cancer survivors fight fatigue, pilot study finds

PEOPLE PRACTICING QIGONGRecovering from a severe illness can take a toll on a person. For older men who have survived prostate cancer and undergone androgen deprivation therapy, lingering effects may include fatigue and associated quality-0f-life issues. A small pilot study in older prostate cancer survivors has found that practicing Qigong – a gentle body-mind practice that incorporates fluid movement, deep breathing and meditation – may be a helpful non-drug tool for relieving this fatigue.

Scientists at the University of New Mexico Cancer Center and the University of North Carolina at Chapel Hill conducted the 12-week randomized controlled trial in 40 men with an average age of 72. All of the participants reported high levels of fatigue at the beginning of the study. One-half of the men engaged in Qigong classes, while the other half participated in a stretching class.

As outlined in the study (subscription required), published in the Journal of Cancer Survivorship, the researchers ”found that the Qigong intervention was associated with significantly larger improvements in fatigue and distress than the stretching group.” The findings, they noted, “are consistent with other Qigong [randomized controlled trials] for cancer survivors and depressed, chronically ill older adults.”

Co-lead author Rebecca Campo, PhD, said in a release, “Qigong may be an effective nonpharmacological intervention for the management of senior prostate cancer survivors’ fatigue and distress.” She added that larger trials and ones that include racially and ethnically diverse participants are needed to confirm the results of the initial trial.

Previously: NIH hosts Twitter chat on using mind and body practices for managing holiday stress and anxietyStudy shows practicing tai chi may increase brain volume in healthy older adults and Study examines the benefits of Tai Chi for the elderly
Photo by ASSOCIATED PRESS

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