The Saturday Essay
Why Women Are Living in the Discomfort Zone
More than 100 million American adults live with chronic pain—most of them women. What will it take to bring them relief?
Several years ago, my neck suddenly went
bonkers—bone spurs and a long-lurking arthritic problem probably
exacerbated by too many hours spent hunching over a new laptop. On a
subjective scale of zero to 10 (unfortunately, there is no simple
objective test for pain), even the slightest wrong move—turning my head
too fast or picking up a pen from the floor—would send my pain zooming
from a zero to a gasping 10.
Sitting in
a restaurant was agony if the table was too high; it forced my arms and
shoulders up. So was sitting in the movies, looking up to see the
screen. Shifting from sitting to lying down in bed was excruciating;
there is simply no way to do it with a bad neck. Even stupid little
things like bending forward to paint my toenails became impossible.
I
had been inducted, apparently, into the growing army of American adults
living in chronic pain. I discovered that there are 100 million of us,
according to the Institute of Medicine. That was surprise No. 1.
Surprise No. 2 was that most of us are women. Nobody really knows why.
There
are cultural factors, to be sure. Women are "allowed" to be emotional
about their pain, and men often aren't, so perhaps women's pain gets
noticed more. There are complicated hormonal factors too. There are
research biases at work as well, including the absurd fact that most
basic neuroscience work on pain pathways is done not only in rats but in
male rats. Go figure.
What is clear is
that women and men can react so differently to both pain and pain
medications that, as the McGill University pain geneticist
Jeffrey Mogil
only half-jokingly puts it, we may someday have pink pills for
women and blue pills for men.
Here's
what we do know. Clinically, women are both more likely to get chronic
painful conditions that can afflict either sex and to report greater
pain than men with the same condition, according to studies over the
past 15 years. (Women also have more acute pain than men even after the
same surgeries, such as wisdom tooth extraction, gall bladder removal,
hernia repair and hip and knee surgery.)
In
2008, when researchers looked at prevalence rates in 10 developed and
seven developing countries, in a sample that included more than 85,000
people, they discovered that the prevalence of any chronic pain
condition was 45% among women, versus 31% among men.
In a 2009 review, researchers from
the University of Florida found that, all over the world, women get more
irritable bowel syndrome, more fibromyalgia, more headaches (especially
migraines), more neuropathic pain (from damage to the nervous system
itself), more osteoarthritis and more jaw problems such as TMD, as well
as more musculoskeletal and back pain. In a large 2012 study (the
biggest of its kind), Stanford University researchers confirmed this
picture.
And it isn't just clinical
pain conditions that reveal an unequal burden of suffering. Sex
differences have also shown up in lab experiments in which people
voluntarily let scientists test their responses to pain stimuli, though
recent research suggests that these differences are more complicated
than once thought.
Historically, women
have repeatedly been shown to be more sensitive to experimental pain
stimuli than men—with lower pain thresholds (that is, they report pain
at lower levels of stimulus intensity) and lower tolerance (they can't
bear intense painful stimulation as long). More recent work shows that
the type of pain stimulus—heat, cold, mechanical pressure, electrical
stimulation, ischemic pain (from tourniquets cutting off blood supply)
and other methods—matters a lot in the attempt to tease out gender
differences.
In a recent systematic
review of 10 years' worth of data from pain labs, Canadian researchers
found that men and women have comparable thresholds for cold and
ischemic pain but that women have lower pain thresholds for
pressure-induced pain than men. It's unclear why. With tolerance, there
is strong evidence, the team found, that women tolerate less heat and
cold pain than men, but that tolerance for ischemic pain is comparable
in men and women. Again, it isn't clear why.
The
more pressing question, of course, for millions of women in chronic
pain is how well their pain will be managed once they seek help.
A
few studies suggest that when women in chronic pain seek care in
emergency rooms, they are offered comparable doses of opioids
("narcotics") as men and sometimes are actually offered more aggressive
treatment. Chronic pain, by the way, isn't just acute pain that doesn't
go away after a few months; it's a transformation of the nervous system
that can literally shrink the brain.
But
many other studies point to undertreatment of women's chronic pain—a
pattern that fits an overall picture of differential care for men and
women. With heart attacks, for instance, a team of Canadian researchers
reviewed the charts of 142 men and 81 women with comparable symptoms and
reported in 2002 that men were more likely to be given lipid-lowering
drugs, to get angiograms (to detect potentially clogged blood vessels)
and to have coronary-artery bypass surgery.
Other
data suggest that women are also less likely than men to be admitted to
intensive care units and to get certain procedures, such as being put
on a respirator, once they arrive there; they are also more likely to
die in the ICU, in the hospital or within a year of admission. A 2007
Rhode Island study looked at 30 men and 30 women who had just had
coronary-artery bypass surgery and tracked the medications they were
given. The researchers were astonished to find that men got pain
medications, while women got sedatives.
With chronic pain problems, women's symptoms are often minimized.
In
a clever 1999 study, researchers from Georgetown University videotaped
professional actors portraying people with chest pain. The researchers
showed the videos to more than 700 primary care physicians and gave them
data about each hypothetical patient. The doctors were much less likely
to believe that the women with chest pain had heart disease. Similarly,
when European researchers looked at the records of 3,779 heart
patients, 42% of them women, they found that women weren't worked up as
thoroughly. It was the same story in a 2000 Mayo Clinic of 2,271 men and
women who went to the emergency room with chest pain.
To
be sure, chest pain and heart attacks can be especially tricky to
diagnose because women and men tend to exhibit somewhat different
symptoms. But less complicated medical problems, such as the knee pain
of osteoarthritis, exhibit the same pattern of differential treatment.
Women
are three times less likely to get the hip or knee replacement they
need, according to
Mary I. O'Connor,
a former Olympic rower who now heads the orthopedic surgery
department at the Mayo Clinic in Jacksonville, Fla. And when they do
finally have the surgery, they often don't do as well as men, a problem
she calls the "never-catch-up syndrome."
Part
of the problem is that women usually wait longer to have surgery, Dr.
O'Connor has found, in contrast to men, who tend to seek surgery before
their pain becomes extreme. The surgery itself is equally beneficial for
both sexes, but because a woman typically has more advanced disease by
the time she gets surgery, the result often isn't as good.
Another
factor may also be at work here: an unconscious bias that can make
doctors less likely to recommend surgery to a woman with moderate knee
arthritis.
In a 2008 study, Canadian
researchers looked into this very question, asking 38 family physicians
and 33 orthopedic surgeons to evaluate one "standardized," or typical,
male patient and one "standardized" female patient with moderate knee
arthritis. ("Moderate" means a degree of arthritis in which it's a
judgment call whether surgery is necessary or not.)
The
odds of a surgeon recommending knee replacement were 22 times higher
for the male patient than the female, the Canadian team found.
Women
are under-treated for abdominal pain, too, a 2008 study showed. In
Philadelphia, emergency room doctors kept track of 981 men and women who
arrived with acute abdominal pain. The men and women had similar pain
scores, but women were significantly less likely to get any kind of pain
medication and were 15% to 23% less likely than men to get opioids
specifically. Women also had to wait longer before they got any pain
medicine—65 minutes on average, compared with 49 for men. Cancer and
AIDS patients have displayed the same pattern, with women much less
likely than men to get adequate pain treatment.
And
consider this: In Sweden, researchers used a modified version of a
national exam for young doctors in which hypothetical patients with neck
pain were described. Some of the hypothetical patients were male and
some female; all were described as bus drivers who were living in tense
family situations. The interns taking the exam were more likely to ask
female patients psychosocial questions (implying a psychosomatic origin
of the pain) and more likely to request lab tests in the males. Female
interns were just as biased as males.
So if women have more chronic pain than men—and they do—the obvious question becomes: Why?
At
the most basic biological level—the expression (activation) of genes,
including genes that control responses to pain stimulation—gender has a
very significant effect.
In fruit
flies, for instance, researchers from North Carolina State University
have shown that males and females are different in the expression of a
whopping 90% of all their genes. In other words, for almost all the
genes in the fly's genome, sex plays a significant role in how active a
particular gene is—that is, how much it is "turned on" and how much of a
role it plays in the animal's physiology and behavior. Exploring such
sex differences in gene expression could help researchers understand
sex-related differences in pain processing.
Sex hormones also play a major role in the
different ways men and women experience pain, though the hormonal
connection is proving nightmarishly tricky to unravel.
It's
clear that, as young children, boys and girls show comparable patterns
of pain—until puberty. Once puberty hits, certain types of pain are
strikingly more common in girls. Even when the prevalence of a pain
problem is the same in both sexes, pain severity is often more intense
in girls than boys. That is especially true with migraines. Before
puberty, boys and girls get roughly the same number. After puberty, the
prevalence becomes 18% for women and 6% or 7% for men. A similar pattern
holds for TMJ, temporomandibular joint disease (now called TMD), as
University of Washington researchers have shown.
Overall,
many researchers think that testosterone generally protects against
pain, an idea shown in some rat studies. If newborn male rats are
castrated, they are unable to produce testosterone later, during
puberty. The result? The animals become less sensitive to the
pain-reducing effects of the opioid, morphine, and thus more susceptible
to pain. If newborn female rats are given testosterone, they get better
pain relief from morphine. (A word of caution, though: It isn't clear
how well pain findings in rats translate to people.)
But
if the role of testosterone in pain is relatively straightforward (more
testosterone, less pain), the role of estrogen is anything but.
Genetics
research suggests that estrogen reduces the activity of one of the
leading "pain genes," called COMT. The job of the COMT gene is to get
rid of stress hormones such as epinephrine. That means that if COMT
activity is too low, the body can't get rid of stress hormones as well.
And since stress hormones act directly on nerves to rev up pain, the net
result of estrogen acting on COMT is more pain, according to
researchers at the University of North Carolina.
Other
research, too, supports the "estrogen is bad " pain theory. Consider
what happens when transsexuals take hormones to enhance the sexual
characteristics of their new sex. In one preliminary study, Italian
researchers tracked male-to-female human transsexuals, who must take
estrogen to enhance female sex characteristics. They found that
approximately one-third develop chronic pain, especially headaches. The
researchers also looked at female-to-male transsexuals, who must take
testosterone to enhance male characteristics; their chronic pain went
down.
But often, things aren't that
simple. At menopause, for instance, women's ovaries stop pumping out
estrogen. To combat the symptoms caused by this drop in estrogen, many
women begin taking exogenous estrogen—that is, estrogen not made
naturally in the body but taken as a drug. If the general theory—that
estrogen increases pain—is true, you would expect that taking exogenous
estrogen (hormone-replacement therapy) would make pain worse. But in
truth, sometimes exogenous estrogen makes pain worse, sometimes it
doesn't, and sometimes it makes it better.
And
then there is the "catastrophizing" problem. In general, studies
suggest that women are more likely than men to catastrophize—that is, to
imagine worst-case scenarios and to believe that the pain will be
unending. The tendency to catastrophize even shows up on brain scans
called fMRIs. In one University of Toronto study, for instance,
researchers showed that while catastrophizing didn't affect how the
brain processed the sensory aspect of experimental pain, it did make the
emotional regions of the brain light up.
Catastrophizing
may actually be a learned behavior; girls, more than boys, seem to pick
up verbal and nonverbal catastrophizing cues about pain from their
mothers, says
Lonnie Zeltzer,
a pediatric anesthesiologist at University of California, Los
Angeles. The good news here is that studies show that cognitive
behavioral therapy can help reduce the tendency to catastrophize.
Where does all this leave women in pain?
To
some extent, in the same boat as men in pain. Both men and women often
have to be extremely persistent in the search for a physician who can
help with their suffering. That is because most doctors don't get enough
basic education about pain in medical school—a sad but well-documented
fact.
But women, I believe, have to be extra-persistent, particularly if they feel their pain is being dismissed as emotional.
I
know, because this happened to me with the first physician I went to
for my neck pain. When she seemed to imply that there was an emotional
trigger for my pain, it felt like she was literally adding insult to
injury. I left that doctor and found another—a man, as it happened—who
believed me and set me on a path of treatment that ultimately worked.
Thankfully, I am much better now.
This
essay is adapted from Ms. Foreman's new book, "A Nation in Pain:
Healing Our Biggest Health Problem," published by Oxford University
Press.
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