Women, at least in America, outlive men by six years.
So how, then, do you account for this:
Women are five times as likely as men to get migraines and osteoporosis, two to three times as likely to get seriously depressed, and much more likely to get diseases like lupus, rheumatoid arthritis and scleroderma, in which the immune system attacks the body’s own organs.
Women are also more susceptible to damage from tobacco and alcohol. In men and women of equal size who consume equal amounts of alcohol, blood levels are higher in women because they metabolize alcohol differently.
Certain biological basics differ, too. Women’s hearts beat faster. And food travels more slowly through women’s intestines, which may explain why they have more constipation and slightly more colon cancer. Women also respond differently to pain and to some anesthetics.
Granted, men fall prey to heart disease earlier in life than women, and they suffer more than their share of cluster headaches and violent deaths, especially when they’re young. But the enigma remains.
How can females — and for that matter, female mammals in general — outlive males, yet have such a disproportionate share of some diseases? Beyond the obvious Adam and Eve stuff, in other words, how do women’s and men’s bodies differ, and how important are these differences to health and medicine?
That’s exactly what researchers in a new field, gender-specific medicine, are trying to find out — a quest with potentially life-saving consequences, because women and men not only get certain diseases at different rates but often have different symptoms for the same disease.
Heart disease, for instance, is the number one killer of both men and women, though women on average get it 10 years later in life because they are protected until menopause, in part by the hormone estrogen.
But unlike men, women often don’t experience the “classic” heart attack symptoms: feeling as if there’s “an elephant on their chest,” or pain radiating down their arms, says Dr. Marianne J. Legato, director of the Partnership for Women’s Health at Columbia University College of Physicians and Surgeons.
Instead, many women, perhaps 15 to 20 percent, feel pain in the upper abdomen and have nausea, sweating and shortness of breath, says Legato, a pioneer in gender-specific medicine. Unless doctors are alert, women’s heart attacks may be dismissed as stomach aches and their breathlessness, as anxiety.
Sex hormones, and the ways they influence immune reactions, metabolism, and other functions, are one major factor in gender differences.
Osteoporosis, for instance, is clearly tied to low levels of estrogen, which is produced by the ovaries and keeps bones strong. The risk of osteoporosis rises steeply at menopause as estrogen levels decline.
Men have less osteoporosis largely because they continue to produce testosterone (which the body converts to estrogen) at a comparatively steady rate throughout life, notes Dr. Andrea Dunaif, chief of the Division of Women’s Health at Brigham and Women’s Hospital.
And it’s not just bones that respond. Receptors for estrogen, androgens and other hormones are scattered throughout the body, and researchers are just beginning to understand why, says Dr. JoAnn Manson, an endocrinologist at Brigham and Women’s and a principal investigator of the Women’s Health Initiative, an ongoing nationwide study of older women.
Perhaps the most puzzling gender differences are those in the immune system, most notably in auto-immune diseases that occur when immune cells and antibodies attack the body’s own tissues. Here, too, some researchers suspect a hormone connection.
“About 90 percent of auto-immune diseases occur more often in women than men,” says Dr. Robert Lahita, chief of rheumatology at St. Luke’s-Roosevelt Hospital in New York.
Women are nine times more likely to get systemic lupus erythematosus, three to four times more likely to get rheumatoid arthritis, four times more likely to get scleroderma, and two to three times more likely to get multiple sclerosis.
Both men and women make so-called TH1 cytokines, which promote inflammation and production of immune cells, as well TH2 cytokines, which stimulate antibodies. Estrogen may trigger extra production of some TH2 cytokines and may also inhibit cells that suppress inflammation, which would contribute to auto-immune disease, Lahita says.
But precisely how hormones influence cytokine production is a matter of debate — and intense research, much of it focused on pregnancy, a time when both hormones and the immune system play out a fascinating and perplexing script.
During pregnancy, levels of estrogen and another hormone, progesterone, are high. But if high estrogen were the sole reason women get more auto-immune diseases than men, you’d think that all that pregnancy would make auto-immune diseases worse. And that isn’t so.
In fact, some auto-immune diseases, like rheumatoid arthritis, actually go into remission, while others, like lupus, do not, notes Dr. J. Lee Nelson, a rheumatologist at Fred Hutchinson Cancer Center in Seattle.
Multiple sclerosis also gets better in some women during pregnancy, but often gets worse again after delivery.
What is clear is that evolution has deemed it important to make these immune shifts in pregnancy — probably for the survival of both mother and fetus.
That’s because some cells from the fetus inevitably cross the placenta and wind up in the mother’s bloodstream. If the mother’s immune system reacted too strongly to these fetal cells, which are half “foreign” because of the father’s DNA, she would reject the fetus, Nelson notes. This means her immune system must become “tolerant” of this foreign tissue. Yet the mother’s immune system can’t become too quiescent or she would come down with endless infections.
Teasing apart the intricate hormonal and immunological shifts during pregnancy has implications not just for women with auto-immune diseases, but for a basic understanding of how gender influences biology.
“Research on women, and the changes in sex hormones at menopause and during pregnancy, has already resulted in a whole new understanding of the importance of these hormones to the functioning of all systems in the body, from brain to skin,” says Legato.
But many questions remain. The big one is why, given the burden of so many gender-specific diseases, do women still live longer than men?
That’s “the great puzzle,” says Wanda Jones, deputy assistant secretary for women’s health at the Department of Health and Human Services.
“And if we understood that better, maybe we could help men live longer.'”
SIDEBAR:
Reconciling differences
Confronting gender-specific medicine:
- If you’re a woman, ask your doctor if that means you should take a different dose of drugs than the package label says and whether you should expect different side effects.
- Remember that alcohol has a more potent effect on women than on men and, cigarette for cigarette, tobacco is more deadly for women, too, not to mention more addictive.
- When you read results from a study done on men, ask your doctor if the results apply to women as well. And vice versa.
- If you’re a woman at risk for heart attack, remember that your symptoms may not be exactly like men’s chest pain, but may be pain in the upper abdomen, nausea, and shortness of breath.
- The need for vitamins and minerals — including supplements — varies by gender, too. In general, adults need 1,000 milligrams a day of calcium, but postmenopausal women need 1,500 a day unless they’re taking estrogen. Men rarely need iron supplements, but menstruating women may. Women of childbearing age may also need 400 micrograms a day of folic acid.
- Migraine headaches, acne, panic attacks, and seizures often get worse just before menstruation. A diabetic woman’s need for insulin may increase at this time, too.
- If you’re a man with heart disease, make sure you’re not being given overly aggressive treatment. Women sometimes get treatment that’s not aggressive enough, but men are sometimes treated too aggressively — with clot-busting drugs, bypass surgery, and other interventions. So ask your doctor.
For more information on the subject, you might want to read “Gender-Specific Aspects of Human Biology for the Practising Physician,” by Dr. Marianne J. Legato, Futura Publishing Co., Armonk, N.Y.