Celiac Disease and NIH Women's Health Research

Signs, Symptoms, and Risk Factors

Celiac disease is a chronic autoimmune condition that occurs in approximately 1% of the U.S. population, and its incidence has been increasing over the past few decades. In people with celiac disease, an immune-mediated response in the small intestine is driven by ingesting dietary gluten, a protein found in wheat, barley, rye, and spelt. This response can damage the intestinal tract via intraepithelial lymphocytosis and villous atrophy, which can lead to malabsorption of essential nutrients. In some cases, poor absorption of micronutrients can cause complications such as anemia, neuropathies, osteopenia, or osteoporosis. Other clinical signs and symptoms of celiac disease include diarrhea, abdominal discomfort, and weight loss.^{1 - 4} Celiac disease has also been associated with certain psychiatric disorders, including anxiety, depression, eating disorders, and attention-deficit/hyperactivity disorder (ADHD), although these associations are not well understood.^{5 , 6}

This condition has a strong genetic component; those who have a parent, sibling, or child with celiac disease have a 10% to 15% higher risk of developing it themselves. People with the human leukocyte antigen (HLA)-DQ2 or HLA-DQ8 haplotypes are predisposed to developing an autoimmune response to gluten, although a substantial number of non-HLA genes have also been linked to this condition.^{2 - 4 , 7} People with certain chromosomal disorders (e.g., Down syndrome) or other autoimmune disorders (e.g., type 1 diabetes) also have a higher risk of celiac disease.^{1 - 3} While gluten is the essential environmental driver, other environmental factors (e.g., those that affect the gut microbiome) are likely involved in the development of this condition.³

Impact on Women's Health

Women are about twice as likely to receive a diagnosis of celiac disease as men.^{3 , 8 , 9} The presenting symptoms of celiac disease seem to be similar between women and men, although one study reported that constipation was more commonly observed in women.⁸ The same study also noted that women were more likely than men to have low levels of ferritin at the time of diagnosis.

When left untreated, the nutritional deficits caused by celiac disease can delay the onset of menarche in girls.^{10 , 11} Some research has also noted a potential association between undiagnosed or untreated celiac disease and female infertility and adverse pregnancy outcomes;¹⁰ in one systematic review and meta-analysis, the risk of having celiac disease was found to be three times higher among women who were experiencing infertility than among controls.¹² Most of the available data suggest that these risks are not higher in women with well-treated celiac disease.

Diagnosis and Treatment

A physical exam can identify some of the signs and symptoms of celiac disease, such as signs of malnutrition, oral ulcers, and dermatitis herpetiformis. Diagnosis generally involves confirming that the patient has elevated levels of the serologic antibody tissue transglutaminase immunoglobulin A (tTG-IgA) and performing esophagogastroduodenoscopy to obtain duodenal biopsies.^{2 , 4 , 13}

Strict adherence to a gluten-free diet can help mitigate the symptoms of celiac disease and prevent damage to the intestines and long-term complications. However, maintaining this diet over the long term can be difficult, and people with this condition often require dietitian support to avoid micronutrient deficiencies. Persistent villous atrophy has been observed in a significant proportion of people with celiac disease even after 2 years of following a gluten-free diet,^{2 , 14} and some people with celiac disease have persistent symptoms despite maintaining this diet. These individuals may have comorbid conditions (e.g., inflammatory bowel syndrome), continued gluten exposure, or refractory celiac disease.^{2 , 15}

Ongoing Research

Because celiac disease can present with a variety of signs and symptoms, diagnosis is often delayed,¹⁶ with some studies reporting that the average time between the appearance of symptoms and diagnosis can be as long as 10 years.^{17 , 18} In addition, women are more likely to have a longer time to diagnosis for celiac disease than men.^{19 , 20} Current research is investigating the potential of new diagnostic strategies for celiac disease, including the use of blood-based assays that can detect gluten‐specific T cells in vitro.²¹

Questions also remain about the potential impacts of celiac disease on menopause and pregnancy.

Researchers supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) are working to understand the underlying mechanisms of tissue destruction and repair in people with celiac disease. The Tissue Destruction and Healing in Celiac Disease clinical trial, which began in 2023, involves a series of gluten challenge and de-challenge studies. The information collected from this trial will clarify how interactions between genetics, microbiota, and the immune system cause the different clinical presentations of celiac disease and affect the severity of tissue damage. The aim of the trial is to develop better resources for managing celiac disease.²²

The Gluten Technology and Education for Celiac Health (GLUTECH) trial, another NIDDK-supported study, is a large-scale clinical trial that is testing the effectiveness of using gluten-detection technologies to manage celiac disease. The researchers are investigating whether combining these technologies with telehealth strategies can improve clinical outcomes among patients who recently received a celiac disease diagnosis. The goal is to provide an accessible option for the long-term monitoring of celiac disease and to reduce both the physical and psychological burdens of this condition.²³