Hormonal Influences on Inflammatory Bowel Diseases

Of the 1.8 million U.S. women with inflammatory bowel diseases (IBD), over half of those who are premenopausal suffer from cyclical menstrual-related IBD symptoms, regardless of how well their disease is controlled. Despite the significant impact that cyclical IBD symptoms have on quality of life, evidence about how to alleviate these symptoms is lacking. In other chronic conditions which are hormonally influenced, such as epilepsy, hormonal contraception may be used to favorably impact disease-related symptoms associated with menses and improve quality of life. Long acting reversible contraception, including the etonogestrel (ENG) contraceptive implant and levonorgestrel (LNG) intrauterine device (IUD), are the most effective contraceptive options with excellent safety profiles and are highly desired if access barriers are removed, thus ideal for study in this population. In our previous cross-sectional study, 47% of the levonorgestrel (LNG) IUD users reported improvement in their cyclical IBD symptoms, but ENG implant use was uncommon and prospective data on the effect of either the IUD or implant on symptoms remain lacking. In order to design a future comparative effectiveness trial on the effect of the ENG implant and LNG IUD on menstrual-related IBD symptoms, the investigators propose this pilot randomized controlled trial with a participant-preference arm to define a feasible study design and recruitment plan, determine metrics to differentiate between non-menstrual and menstrual-related IBD symptoms, and explore the potential role of use of inflammatory markers in future trials. The investigators will recruit participants from the University of Utah IBD Center and clinics and through social media ads. Total study commitment will be ~8 months which includes two spontaneous menstrual cycles prior to contraceptive initiation and then six months of follow-up. Study activities will include daily and weekly text message surveys, as well as blood draws and fecal samples for inflammatory markers commonly used for IBD management. Our aims include: (1) To determine acceptability of randomization to the ENG contraceptive implant or 52mg-LNG IUD and in those who decline, acceptability of participation in a participant-preference arm, (2) To obtain estimates of means and standard deviations in established IBD symptom scales (Harvey Bradshaw and partial Mayo) and IBD quality of life measures across the phases of two menstrual cycles and then for 6 months after contraceptive method initiation, and (3) To obtain preliminary estimates of inflammatory marker variation across menstrual phases and pre- and post- contraceptive initiation. This pilot will inform a future trial design and this line of inquiry will allow for an adjuvant approach for IBD symptom management that is sex-specific and addresses both concerns for hormonal triggers and the need for highly-effective contraception for those who desire it.

Inclusion Criteria:Between 18-45 years oldFluent in English and/or SpanishHave biopsy-proven IBDHave a regular menstrual cycle (21-35 days)Report recurrent cyclical IBD symptoms in >50% of menstrual cycles in past 6 months (e.g. change in bowel habits, abdominal pain, etc.)Intend to use a LNG IUD or ENG implant and willing to consider randomizationNot at risk for pregnancy (e.g. sterilization, same-sex partner, abstinence) or willing to use condoms until 7 days after LARC device initiationExclusion Criteria:Current pregnancy (+urine pregnancy test in clinic)Breastfeeding without resumption of 2 normal mensesContraindication to ENG implant or LNG IUD (U.S. Medical Eligibility Criteria for Contraceptive Use13 category 3 or 4)History of intolerance/ side effects with ENG Implant/LNG IUDVaginal bleeding of unknown etiologyUse of contraceptive steroids in past 30d without resumptions of mensesActive, steroid-requiring IBD flare in past 30 days