More than 20 million Americans have gallstones, and approximately 1 million are diagnosed each year. However, only 1% to 3% of the population complains of symptoms during the course of a year, and fewer than one half of these people have symptoms that return.
Risk Factors in Women
Women at all ages are much more likely than men to develop gallstones. Gallstones occur in nearly 25% of women in the United States by age 60, and as many as 50% by age 75. In most cases, they have no symptoms. In general, women are probably at increased risk because estrogen stimulates the liver to remove more cholesterol from blood and divert it into the bile.
Pregnancy increases the risk for gallstones, and pregnant women with stones are more likely to develop symptoms than women who are not pregnant. Surgery should be delayed until after delivery if possible. In fact, gallstones may disappear after delivery. If surgery is necessary, laparoscopy is the safest approach.
Hormone Replacement Therapy
Several large studies have shown that the use of hormone replacement therapy (HRT) doubles or triples the risk for gallstones, hospitalization for gallbladder disease, or gallbladder surgery. Estrogen raises triglycerides, a fatty substance that increases the risk for cholesterol stones. How the hormones are delivered may make a difference, however. Women who use a patch or gel form of HRT face less risk than those who take a pill. HRT may also be a less-than-attractive option for women because studies have shown it has negative effects on the heart and increases the risk for breast cancer.
Risk Factors in Men
About 20% of men have gallstones by the time they reach age 75. Because most cases do not have symptoms, however, the rates may be underestimated in older men. One study of nursing home residents reported that 66% of the women and 51% of the men had gallstones. Men who have their gallbladder removed are more likely to have severe disease and surgical complications than women.
Risks in Children
Gallstone disease is relatively rare in children. When gallstones do occur in this age group, they are more likely to be pigment stones. The following conditions may put children at higher risk:
- Spinal injury
- History of abdominal surgery
- Sickle-cell anemia
- Impaired immune system
- Receiving nutrition through a vein (intravenous)
Because gallstones are related to diet, particularly fat intake, the incidence of gallstones varies widely among nations and regions. For example, Hispanics and Northern Europeans have a higher risk for gallstones than do people of Asian and African descent. People of Asian descent who develop gallstones are most likely to have the brown pigment type.
Native North and South Americans, such as Pima Indians in the United States and native populations in Chile and Peru, are especially prone to developing gallstones. Pima women have a 70% chance of developing gallstones during their lives, and a majority of native Indian females in Chile and Peru develop gallstones. These populations also have a high incidence of gallbladder cancer. In Chilean women, gallbladder cancer is the most common cause of cancer death, ahead of breast, lung, and cervical cancer.
Having a family member or close relative with gallstones may increase the risk. Up to 33% of cases of painful gallstones may be related to genetic factors.
A mutation in the gene ABCG8 significantly increases a person's risk of developing a certain type of gallstones. A single gene, however, does not explain the majority of cases, so multiple genes and environmental factors play a complex role.
Defects in transport proteins involved in biliary lipid secretion appear to predispose certain people to gallstone disease, but this alone may not be sufficient to create gallstones.
Cholesterol gallstones are more prevalent in people who consume Western diets of high amounts of saturated fats and cholesterol, protein, and refined sugars, and low amounts of fiber as well as a high total calorie count.
People with diabetes are at higher risk for gallstones and have a higher-than-average risk for acalculous gallbladder disease (without stones). Gallbladder disease may progress more rapidly in patients with diabetes, who tend to have worse infections.
Obesity and Weight Changes
Being overweight is a significant risk factor for gallstones. In such cases, the liver over-produces cholesterol, which is delivered into the bile and causes it to become supersaturated.
Rapid weight loss or cycling (dieting and then putting weight back on) further increases cholesterol production in the liver and an increased risk for gallstones.
- The risk for gallstones is as high as 12% after 8 to 16 weeks of restricted-calorie diets.
- The risk is more than 33% within 12 to 18 months after gastric bypass surgery.
About 30% of gallstone cases in these situations have symptoms. The risk for gallstones is highest in the following dieters:
- Those who lose more than 24% of their body weight
- Those who lose more than 1.5 kg (3.3 lb.) a week
- Those on very low-fat, low-calorie diets
Men are also at increased risk of developing gallstones when their weight fluctuates. The risk increases proportionately with dramatic weight changes as well as with frequent weight cycling.
Patients who have either Roux-en-Y or laparoscopic banding bariatric surgery are at increased risk for gallstones. For this reason, many centers request that patients undergo cholecystectomy before their bariatric procedure. However, doctors are now questioning this practice.
Metabolic syndrome is a cluster of conditions that includes obesity (especially belly fat), low HDL (good) cholesterol, high triglycerides, high blood pressure, and high blood sugar. Research suggests that metabolic syndrome is a risk factor for gallstones.
Low HDL Cholesterol, High Triglycerides and Their Treatment
Although gallstones are formed from the supersaturation of cholesterol in the bile, high total cholesterol levels themselves are not necessarily associated with gallstones. Gallstone formation is associated with low levels of HDL (good) cholesterol and high triglyceride levels. Some evidence suggests that high levels of triglycerides may impair the emptying actions of the gallbladder.
Unfortunately, fibrates (drugs that may be used to correct these abnormalities) increase the risk for gallstones by boosting the amount of cholesterol secreted into the bile. These medications include gemfibrozil (Lopid) and fenofibrate (Tricor). Other cholesterol-lowering drugs do not have this problem or may even decrease the risk for gallstones, which is the case for statins.
Other Risk Factors
Prolonged Intravenous Feeding
Prolonged intravenous feeding reduces the flow of bile and increases the risk for gallstones. Up to 40% of patients on home intravenous nutrition develop gallstones within 3 to 4 months, and the risk may be higher in patients on total intravenous nutrition.
Crohn disease, an inflammatory bowel disorder, leads to poor reabsorption of bile salts from the digestive tract and substantially increases the risk for gallbladder disease. Patients over age 60 and those who have had numerous bowel operations (particularly in the region where the small and large bowel meet) are at especially high risk.
Cirrhosis poses a major risk for gallstones, particularly pigment gallstones.
Bone marrow or solid organ transplantation increases the risk of gallstones. The complications can be so severe that some organ transplant centers require the patient's gallbladder to be removed before the transplant is performed.
The following drugs may increase the risk for gallstones:
- The somatostatin analog octreotide (Sandostatin).
- Fibrates, a type of lipid-lowering agents.
- Estrogen, whether administered as oral contraceptive to premenopausal women or as hormone replacement therapy to postmenopausal women.
- Thiazide diuretics.
- The antibiotic ceftriaxone.
Chronic hemolytic anemia, including sickle cell anemia, increases the risk for pigment gallstones.
Spinal Cord Injury
People with spinal cord injury have a higher prevalence of gallstones and a higher rate of complications from gallstone disease.
High consumption of heme iron, the type of iron found in meat and seafood, has been shown to lead to gallstone formation in men. Gallstones are not associated with diets high in non-heme iron foods such as beans, lentils, and enriched grains.