Texas Medical School Alum and former Internal Medicine resident at the University of Texas Southwestern Medical School, Dr. Hamed Khalili, MD, MPH, is seeing renewed interest in one of his previously published scientific studies entitled, “Oral contraceptives, reproductive factors and risk of inflammatory bowel disease,” from both US and UK science media outlets. The study which was first published in the May 2012 on-line edition of Gut aimed to determine whether there was an associative risk with oral contraceptive use and the diagnosis of inflammatory bowel disease (IBD), independent of other lifestyle factors.

IBD is a debilitating disease caused by chronic inflammation throughout all or part of a patient’s digestive tract.  It includes:

• Ulcerative colitis (UC): causes long-lasting inflammation and sores (ulcers) in the innermost lining of the large intestine (colon) and rectum.
• Crohn’s disease (CD): causes inflammation of the lining of the digestive tract. In Crohn’s disease, inflammation often spreads deep into affected tissues. The inflammation can involve the large intestine, small intestine or both.

Women are more likely to be diagnosed than men with IBD. Studies conducted in the 1990s have shown an association between oral contraceptive use and the risk CD and UC. Unfortunately, despite continued investigation, it is still unclear whether this association is independent or in relationship to lifestyle factors or reproductive status.

The 2012 study made an important and significant contribution to the literature because it attempted to examine oral contraceptive use and risk of CD or UC in relation to important lifestyle and reproductive factors.

To examine this association, Dr. Khalili and his collaborators looked through the medical records of 232,452 women taking part in the Nurse’s Health Study, a cohort of female registered nurses between the ages of 25-55.  These women had no prior history of UC or CD at the beginning of the observation period, and they provided information every 2 years from 1984 to 2007 on the following: age at menarche, oral contraceptive use, pregnancy status, number of pregnancies, menopause status and other lifestyle risk factors, and diagnosis of CD or UC.

The main study finding showed a significant association between oral contraceptive use and risk of CD in comparison to women who never used oral contraceptives.  Other important findings included:

• There were no significant differences between the groups according to pregnancy, age at menarche, age at birth of first child and smoking.
• Among the sample population 392 cases of UC and 315 cases of CD were observed.
• In comparison to never users, past and current users of oral contraceptive were on average younger and less likely to be overweight or postmenopausal.
• Compared with never users, past and current users of oral contraceptives had a higher risk of developing UC, but the findings were not statistically significant.
• Pregnancy, age at menarche and age at first birth were not associated with risk of CD.
• Among women who either previously or currently smoked, use of oral contraceptives was associated with a higher risk for UC.
• There was no statistically significant association between oral contraceptive use and risk of UC among women who never smoked.
• The risk of CD did not appear to differ according to smoking status.
• The effect of oral contraceptive use on risk of CD or UC did not appear to be impacted by BMI or age.

In a statement about the study’s results, Dr. Khalili said, “What’s very clear is that Crohn’s is not caused by oral contraceptive use by itself. It’s a combination of oral contraceptive use among individuals with a strong genetic predisposition to Crohn’s. It’s an interaction between these two that significantly increases the risk of an individual developing it.”

In a recent letter to the editor in reference to this stud,y Dr. Khalili and his collaborators were advised to further evaluate the link between oral contraceptive (OC) use and risk of Crohn’s disease according to the anatomical location of disease involvement and the gut microbiome. In response to the suggestion, Dr. Khalili stated, “recent data have linked modification in the gut microbiome to endogenous levels of androgens, which are also known to be altered with OC use and influence the development of autoimmune diseases. This supports the intriguing hypothesis that the gut microbiome lies at the crossroads of pathways linking exogenous hormone use with innate and adaptive immunity.”

For patients with IBD and their healthcare providers the hope is that this renewed interest may lead to the development of new treatment options, as well as interventions that may prevent IBD.

About Dr. Khalili

Dr. Khalili, is currently a gastroenterologist and instructor of medicine at Massachusetts General Hospital in Boston. His research interests include clinical and translational research in the field of IBD; with a specialized focus on understanding the environmental factors, such as dietary, reproductive, and lifestyle choices, and their interplay with common genetic risks, as well as the gut microbial environment on the risk and progression of IBD.

About the Nurse’s Health Studies

The Nurses’ Health Studies are among the largest and longest running investigations of factors that influence women’s health. Started in 1976 and expanded in 1989, the information provided by the 238,000 dedicated nurse-participants has led to many new insights on health and disease. While the prevention of cancer is still a primary focus, the study has also produced landmark data on cardiovascular disease, diabetes and many other conditions. Most importantly, these studies have shown that diet, physical activity and other lifestyle factors can powerfully promote better health.