Hello, His and Her Healthcare
Medicine now recognizes that women are different
A man's heart is not a woman's heart; his pain is not her pain. And a standard response to a common medical complaint might work for him--and kill her. Just ask Denise Weiss, who, at 42, was struck by a sensation akin to someone's hand "squeezing the inside of your chest." A trip to the emergency room near her Beverly Hills, Calif., home found nothing, and a subsequent angiogram was clear. It wasn't until 18 months later, when she found a doctor attuned to heart disease's different faces, that she was diagnosed with microvascular dysfunction--a dangerous constricting or clogging of the heart's tiniest arteries that disproportionately affects women and can lead to a heart attack.
Only recently has medicine begun to acknowledge that the wondrous differences between men and women go well beyond size and body parts and a willingness to ask for directions. But things are changing fast now--and the implications for diagnosing, preventing, and treating disease are potentially huge. "The name of the game is to compare men and women and to define the unique characteristics of both," says Marianne Legato, founder of Columbia University's Partnership for Gender-Specific Medicine. Understanding the role that genetics and hormones play in the way illness develops and responds to treatment has obvious benefits for women's quality and length of life, and implications for men's health, too. Might breast cancer and osteoporosis act differently in them?
Cardiac health, traditionally considered a man's concern, has been one of the most fruitful areas of research and one of the most urgent. Heart disease kills more women than all types of cancer put together; in diabetic women, the risk of coronary artery disease rises sixfold, while in diabetic men, it doubles. Yet when women show up with symptoms that don't conform to the male standard--nausea, sweating, or shortness of breath are often female signals of heart attack, for example, rather than the classic burning pain in the chest or arm--their worries are often dismissed. Even when they do report similar symptoms, the complaints may be ignored: One recent European study found that women are less likely than men to receive treatment for angina, the chest pain that signals heart trouble.
Her heart. Yet we now know that profound differences characterize heart disease in men and women, says Mariell Jessup, medical director of the heart failure and transplant program at the Hospital of the University of Pennsylvania. The way women's hearts respond to high blood pressure--they develop thicker walls than men's hearts do, which make the heart less able to relax--puts women at higher risk of heart failure, for example. And, like Denise Weiss, women are far more likely than men to have coronary microvascular dysfunction even as their major arteries remain clear of fatty plaques. Indeed, some cardiologists think women should be screened using more sophisticated tests than angiograms. "It's possible that this should become standard testing,"says Weiss's doctor, Noel Bairey Merz, medical director of women's health at Cedars-Sinai Medical Center in Los Angeles and chair of a large study tracking women with heart problems.
It's certain that women should insist on being heard. "I had symptoms of heart palpitations for between six months and a year," says Jean Horgan, 63, of Wilmington, Del. "I'd seen an internist and had a stress test, and all they kept saying was that there's nothing there. They'd get this look on their faces like 'Here comes another one.'" When she saw Columbia's Legato, though, she was diagnosed with a faulty heart valve that was allowing blood to leak back into the heart, a condition less common in men. Medication, Horgan says, has made "a world of difference."
The reasons for all these variations are still being teased out. Hormonal changes--specifically, a loss of estrogen--were long the chief suspect in heart disease, since problems in women tend to show up with greater frequency after menopause. Yet Merz thinks microvascular dysfunction may have more to do with some intrinsic difference in the way male and female blood vessels behave--which might also explain why migraine and the pale hands and feet that result from blood vessel constrictions are more common in women. Researchers are looking into whether ACE inhibitors and statins, now used in people with blockages in big vessels, might be effective treatments.
Likewise, estrogen loss does not seem to be the chief culprit behind older women's rise in blood pressure. Hypertension is more of a male issue through middle age, but women a decade past menopause have pulled into the lead. That slow ramp-up is too gradual to implicate estrogen loss by itself, says Jane Reckelhoff, a physiologist at the University of Mississippi Medical Center. The male sex hormone testosterone, which women also produce, drops at menopause but then rises and could be more to blame: It may increase "oxidative stress," in which certain molecules damage cells, and which can lead to high blood pressure.
Because men and women have different sex chromosomes, genetic differences are thought to play a role in many illnesses, too. Autoimmune diseases, in which the body's immune system attacks its own tissues, affect mostly women: Lupus, which can damage the joints and multiple organs, afflicts nine times as many women as men, for example; twice as many women as men get multiple sclerosis. Because females receive an X chromosome from each parent but need just one to develop normally, one is randomly inactivated during early embryonic development. However, "genes can escape the inactivation," says Michael Lockshin, director of the Barbara Volcker Center for Women and Rheumatic Diseases at the Hospital for Special Surgery in New York. When a gene is expressed twice, the body may fight resulting proteins it perceives as alien.
Triggers. Another theory holds that stray fetal cells circulate in a woman's body long after childbirth and might trigger the body to attack itself. It's likely that other factors, including environmental causes, are also involved since women and men tend to be exposed to toxins differently, says Lockshin. He recalls an outbreak of an autoimmune disease in Spain that affected mostly women. The culprit was contaminated cooking oil; women were the ones stirring and tasting before the contaminants were destroyed by heat.
Pain provides a good example of how hormones and genes work together. Women suffer pain more often than men by a margin of as much as 10 to 1, says Jeffrey Mogil, who runs the pain genetics lab in the department of psychology at McGill University in Montreal. Perceived intensity also varies; pressure and electrical stimulation seem to hurt women more than men, while extreme heat or cold affects the sexes similarly. Hormones certainly bear some responsibility: The drop in estrogen before a woman's period may account for a temporary increase in sensitivity to pain (one reason that time is a good one to avoid an eyebrow wax). But what is also now understood, says Mogil, is that different genes are responsible for processing pain in men and women.
"The brain is simply wired up differently to process pain from the get-go," he says. (To capture those differences in basic research, Mogil is on a crusade to persuade scientists to use female mice as well as males in their labs.) Someday, that may mean sex-specific painkillers. For now, research is focused on how existing drugs work differently in men and women. One class of painkillers called kappa opioid agonists, sometimes prescribed for post-surgical or cancer pain, is already known to help women more effectively than men.
Indeed, researchers are investigating how all sorts of drugs affect the sexes differently. How are they absorbed at different rates in the gut? How do proteins that transport and activate the drugs act differently in men and women? Women tend to require higher doses of Valium than men, because they more quickly metabolize it. But they are slower to metabolize certain antibiotics. Gail Anderson, a pharmacologist at the University of Washington in Seattle, has surveyed 163 drug applications featuring a sex analysis that were reviewed by the FDA in a five-year period. Eleven showed a difference of more than 40 percent in their action in men and women.
One study led by Susan Kornstein, executive director of the Institute for Women's Health at Virginia Commonwealth University, found that premenopausal women responded better than men to Zoloft, one of the class of antidepressants called selective serotonin reuptake inhibitors (SSRIs), while men responded better to imipramine, one of the tricyclic antidepressants. Postmenopausal women responded to both. (Other studies of these differences have been inconclusive.) Another recent study showed aspirin cuts the risk of heart problems in both men and women but in different ways: In men, it cuts the odds of a heart attack, and in women, the risk of stroke.
Cancer, too, behaves differently in men and women. While colorectal cancer is more common in men, for example, women tend to develop polyps higher in the colon, where they are less likely to be detected by one kind of test, a flexible sigmoidoscopy. A study last year recommended that women choose the more comprehensive colonoscopy instead. Women tend to get lung cancer at an earlier age and are more likely to develop the kind that isn't associated with smoking--but they also have better survival rates. "Right now we don't have anything where you'd treat a man differently from a woman in any type of cancer,"says Kathy Albain, an oncologist at Loyola University in Chicago. But she and other researchers are working on it.
Women only. Albain, for example, is helping to direct a women-only trial of Xyotax, a drug that appeared in two previous studies to do a better job of extending survival in women with lung cancer than in men. One theory: Estrogen may boost an enzyme required to make the drug active. Tailoring cancer treatments to gender may be just a way station en route to much more personalized treatments, in which a tumor's genetic blueprint dictates the drug of choice.
Mental disorders most likely affect sexes differently for both biological and social reasons. Girls report more depression than boys starting in puberty, for example; about twice as many women as men will be diagnosed with depression during their lifetime. A host of biological causes are suspected, says Legato, including sex-specific genes, hormones, and differences in brain chemistry. Stress can play a more significant role in setting off depression in women, perhaps for social and cultural as well as biological reasons. It's been more socially acceptable for women to ask for help with depression, for example. "Women have larger social networks, and they support us, but when something adverse happens to the individuals in the network," its members are affected, says Carolyn Mazure, director of women's health research at Yale. "It's the cost of caring." Women are also more likely than men to fall victim to Alzheimer's.
The benefits to men of gender-specific medicine may someday include an understanding of why more male fetuses miscarry, why boys have more developmental disabilities than girls, and why women outlive men. At the moment, researchers are looking at what happens in men with osteoporosis, since they are more likely than women to die following a hip fracture--even though many more women suffer from bone loss. For now, both men and women should be aware that their gender is probably influencing their health--and their healthcare. Women still tend to receive less thorough evaluations and fewer treatment options than men for the same problems, says VCU's Kornstein.
That isn't likely to happen to Weiss again. She left her job as an asset analyst, which demanded a lot of stressful commuting and travel time, and she is now taking medication, exercising again, and being monitored--and she's greatly relieved to know what's going on. "Women need to become aware of problems like this," she says. "My doctors weren't inadequate. They were just not looking for things that men don't have."
Heart disease typically strikes women a decade later but kills more women yearly than men.
After drinking the same amount of alcohol, women have higher blood alcohol than men of the same age.
Women tend to get lung cancer younger than men do--and they respond better to therapy.
Depression is twice as likely in women as in men. Parenting increases her risk--but not his.
Women have different heartbeat rhythms from men and are more likely to develop heart arrhythmias.
Women are 2.7 times more likely than men to develop autoimmune diseases like multiple sclerosis.
Once they're a decade past menopause, more women have high blood pressure than men.
Women feel pain more often and more intensely than men--and respond better to certain pain medications.
Health facts provided by the Society For Women's Health Research and Marianne Legato
This story appears in the March 6, 2006 print edition of U.S. News & World Report.