Women comprise the majority of health care consumers in the world, but still the minority of the medical evidence base.
“Women are treated based on male data. … The pipeline for getting clinical data is lined with males—male animals, male cells,” Marjorie Jenkins, MD, FACP, said at the annual meeting of the American Medical Women's Association (AMWA). “There are important evidence-based health differences between men and women, and it's been emerging over the past quarter-century.”
Dr. Jenkins, chief scientific officer of the Laura W. Bush Institute at Texas Tech Health Sciences Center in Lubbock, was the keynote speaker at the conference, which was held in Philadelphia in March.
She and other physician lecturers discussed ways that women's health differs from men's, both generally and in a number of specific conditions, including liver disease, kidney disease, and digestive and eating disorders.
They urged physicians to take these differences into account in their daily practice. “Everyone is impacted by this issue,” said Dr. Jenkins. “One-sex medicine doesn't help everyone.”
Livers and kidneys
Although alcoholic liver disease is more common in men than women, women's livers seem to be more susceptible to damage from alcohol or medication, explained Dina Halegoua-De Marzio, MD, a gastroenterologist, hepatologist, and assistant professor at Thomas Jefferson University in Philadelphia.
“Women have a much more rapid progression of alcoholic liver disease with a shorter period of drinking and less daily alcohol intake,” she said. “There are a few reasons for this. Women have increased susceptibility due to higher blood levels, due to lower body mass, and also decreased gastric digestion of alcohol.”
Drug-induced liver injury, from a medication or an herbal supplement, for example, is more common in women than men and typically more severe. “The thought is this is due to differences in drug bioavailability and metabolism,” said Dr. Halegoua-De Marzio. “The pharmacokinetics behind it is not well studied.”
The data are also uncertain about whether there's any association between sex and nonalcoholic fatty liver disease (NAFLD). Use of hormone therapy or oral contraceptives may reduce risk of NAFLD, but that's not definitively proven, she said.
There is strong evidence of a link to another women's health problem: polycystic ovarian syndrome (PCOS). “The one specific relationship I want you to pay attention to is the connection of PCOS and nonalcoholic fatty liver disease. We know that PCOS is frequently accompanied by metabolic complications like insulin resistance, which are the same causes of NAFLD,” said Dr. Halegoua-De Marzio.
Given this connection, patients with PCOS should be screened for NAFLD and vice versa, she advised. Other sex differences in liver-related screening include that, although hepatocellular carcinoma is more common in men than women, women with cirrhosis may be more likely to develop some other types of cancer, including those associated with tobacco use.
“They're at an increased risk of lung, oral, esophageal, and laryngeal cancer. So it's important to be screening those patients,” she said. Bone density should also be screened. Cirrhosis affects bone health in both men and women, but given the generally higher rate of osteoporosis in women, they are at particular risk, Dr. Halegoua-De Marzio noted.
Most of these gender gaps are biological, but the differences in liver transplant rates may be the fault of the health care system, specifically the Model for End-Stage Liver Disease (MELD) score.
“Women are less likely in three years of being listed to receive a liver transplant. They're more likely to die waiting for a liver. Part of this may due to the fact that they have lower MELD scores, because creatinine is one of the major factors in the MELD score, and in women with lower muscle mass, they are obviously going to have a lower creatinine level,” Dr. Halegoua-De Marzio said. “It's a very imperfect system, and something that needs to be looked at in the future.”
Women are also less likely to get kidney transplants, according to Yasmin Brahmbhatt, MD, a nephrologist and assistant professor of medicine at Thomas Jefferson University who spoke at the meeting about chronic kidney disease.
“Women are less likely to be kidney transplant recipients, and that goes for living transplants as well as deceased donor transplants, and women are more likely to donate a kidney than men,” she said. Theories range from the antibody effects of pregnancy to physician referral rates to the suggestion that women “have a more giving nature than men,” said Dr. Brahmbhatt.
There are also fewer women than men on dialysis, despite higher rates of chronic kidney disease. “In high-income countries, 61 million women have chronic kidney disease compared to 48 million men. And in low- and middle-income countries, 210 million women have chronic kidney disease, compared to 177 million men,” she said. “It currently is a public health problem throughout the world.”
The good news on women with chronic kidney disease is the increasing evidence supporting the safety of pregnancy for them, even when on dialysis. “There is so much literature about how we have to change our counseling policies for women who are pregnant or wish to pursue pregnancy,” said Dr. Brahmbhatt. “We have to make a combined decision with our patients, instead of making it for them.”
Important pearls about pregnancy include that women with kidney disease may not realize they are pregnant, because they often have altered menstruation, and that pregnancy tests may not work in dialysis patients, because their human chorionic gonadotropin levels are always elevated.
All pregnancies in women with kidney disease are considered high-risk, and some women may have to spend up to 40 hours a week on dialysis to keep their blood urea nitrogen levels below the target of 45 mg/dL. “I had a patient who underwent a successful pregnancy with a similar dialysis regimen,” said Dr. Brahmbhatt, noting that some patients will make significant sacrifices of their time and health to have a baby.
Women with inflammatory bowel disease (IBD) often have concerns about pregnancy, according to Cuckoo Choudhary, MD, FACP, a gastroenterologist and associate professor at Thomas Jefferson University.
“They are afraid: ‘Will pregnancy worsen my IBD? What will be the effect on my fetus? What are the chances that I'll transmit my disease to my offspring?’” she said.
Patients can be reassured that IBD is unlikely to affect their fertility unless they've undergone surgery for ulcerative colitis (in which case adhesions may be an obstacle) or Crohn's disease and that the risk of a child developing IBD from one parent having it is relatively low (under 20%), she reported.
That's not to say that patients with IBD should start trying for a baby willy-nilly. “Preconception counseling is the key—extremely important. It gives the GI doctor another chance to discuss things with the patient,” said Dr. Choudhary. Topics to discuss include that some medications used for IBD affect fertility in men and women, while a few are contraindicated in pregnancy.
IBD can get better or worse during pregnancy and is associated with some complications that should be mentioned during preconception counseling, she said. “It can increase the risk of spontaneous abortion, preterm birth, low-weight babies, but not any increased risk for any congenital abnormality. We've got to tell that to our patients. Mother's health before and during pregnancy is the most important factor.”
Women with IBD may be leery of even the step before pregnancy, Dr. Choudhary noted. “They tend to avoid intercourse. Why? Fear of intimacy, body image, sickness, fatigue, fear of urgency, medication side effects, depression,” she said.
Other manifestations of IBD that particularly affect women include the skin and eyes. “Uveitis, scleritis, episcleritis, erythema nodosum, pyoderma gangrenosum, cutaneous Crohn's—all more common in females,” said Dr. Choudhary. Men, on the other hand, are more likely to have primary sclerosing cholangitis and ankylosing spondylitis.
The long-term effects differ, too. “Males with IBD are more likely to die of colorectal cancer. Females with IBD are more likely to die of pulmonary complications,” she said.
In addition to keeping an eye out for these risks, physicians should screen women with IBD for anemia, vitamin D deficiency, and low bone density. “Make sure you measure plasma hydroxyvitamin D at diagnosis and then annually. Have a low threshold to get a DEXA [dual-energy X-ray absorptiometry] scan,” advised Dr. Choudhary.
Women with celiac disease face some of the same problems, according to Stephanie Moleski, MD, a gastroenterologist and assistant professor at Thomas Jefferson University. “Iron deficiency is a really important topic, especially for our women. It's the most common clinical presentation of celiac disease in adults, and more so in female patients,” she said.
The presentation of celiac disease differs between men and women, Dr. Moleski reported. “Our female patients are going to be more likely to present with abdominal pain and constipation, as well as iron deficiency anemia, whereas men will present more with elevated liver enzymes, weight loss, and dermatitis herpetiformis.”
Once women have been diagnosed with celiac disease, remember that they are at increased risk of having low bone density. “It's secondary to vitamin D deficiency and malabsorption of calcium and magnesium and a chronic inflammatory state,” said Dr. Moleski. She recommended giving patients DEXA scans a year or two after diagnosis to check for osteoporosis due to malabsorption.
Celiac disease may also be linked to anorexia nervosa, according to some recent research. “A large study out of Sweden found that women with anorexia have twice the odds of a later diagnosis of celiac disease,” said Dr. Moleski. “Conversely, women with celiac disease are 46% more likely to be later diagnosed with anorexia.”
Because the link goes both ways, it's difficult to interpret. “One thought is that maybe these women were misdiagnosed and they had celiac disease all along,” she said. However, it could also be that the treatment for celiac disease—total avoidance of gluten—could increase one's risk for anorexia.
“Maybe this overemphasis on diet at such a young age is leading these women to have eating disorders,” said Dr. Moleski. “There has been recent data looking at patients who have hypervigilance with their gluten-free diet having a lower quality of life, so that's something to be concerned about as well.”
Physicians should generally be concerned about their patients' risk of eating disorders, said Theresa Rohr-Kirchgraber, MD, FACP, during an AMWA talk on the subject.
“I ask you all to take home just two simple questions and ask these in your offices. The first question: ‘Are you comfortable with your current body, shape, and size?’ … The second question: ‘What have you done in the last year to try and change it?’” said Dr. Rohr-Kirchgraber, who is an associate professor of clinical medicine and pediatrics at the University of Indiana in Indianapolis.
The answers to those questions should highlight red flags, such as a patient being not only uncomfortable with her body but unable to name a single part she likes. Or a patient may be unusually specific in a report of recent eating. “When your patient can say, ‘Four almonds, three raisins, one-half cup of rice, and a head of lettuce,’ when they can document it that well that quickly, that should set off warning bells,” Dr. Rohr-Kirchgraber said.
On the other hand, sometimes details are necessary. She described a recent experience discussing turkey sandwiches with two very different patients. An anorexic patient's sandwich was “a slice of bread and one slice of turkey meat, no condiment, and she maybe didn't even eat all the bread.” On the other hand, an obese patient also reported eating a turkey sandwich. “His wife hits him and says, ‘Tell her how you made that sandwich,’” said Dr. Rohr-Kirchgraber. “It's a loaf of bread, three pounds of turkey, and a jar of mayo.”
Although the latter patient's problem of eating too much may be the more common challenge in practice today, physicians should continue to be on the alert for the opposite in their female patients.
“We know that 91% of college-age women have been on a diet within the last two years. … We know that 35% of dieters develop pathological dieting practices,” said Dr. Rohr-Kirchgraber. “One out of every 200 women has at some point had some relationship with anorexia, and a fair number have suffered from bulimia.”