Inflammatory bowel disease (IBD) is comprised of two gastrointestinal disorders— ulcerative colitis and Crohn’s disease—which have distinct clinical and pathological features. Ulcerative colitis is characterized by relapsing and remitting episodes of inflammation limited to the superficial mucosal layer of the large bowel (colon or rectum), whereas Crohn’s disease is characterized by inflammation throughout the bowel layers and may involve any segment of the gastrointestinal tract from oral cavity to anus [1]. Common symptoms of both disorders include diarrhea, rectal bleeding, frequent bowel movements, weight loss, fatigue, and anemia [2,3]. Through clinical evaluation, endoscopy, imaging, and biopsy, clinicians can usually differentiate between ulcerative colitis and Crohn’s disease [4]. IBD often presents during the reproductive years. The peak age of incidence of Crohn’s disease is during the third decade of life, with decreasing incidence afterward, and the incidence of ulcerative colitis is stable between the third and seventh decades [2]. Globally, 59 per 100,000 individuals had IBD in 2019, with variation by country, and slightly higher prevalence among women than men [5].

Although the etiology of IBD remains unknown, genetic and environmental factors are thought to contribute to its development. One risk factor for onset of disease includes oral contraceptive (OC) use, with stronger evidence of an association in studies published before compared with after 2000, possibly because of different OC doses [6,7]. The mechanism through which OC use influences development of IBD is not known, however proposed theories include effects of exogenous estrogen on immunomodulation, intestinal wall function, gut microbiome, and hypercoagulability [8]. Since OC use is considered a risk factor for disease onset, it is reasonable to consider that OC use among women with IBD might result in exacerbation of symptoms or disease relapse.

Individuals with IBD have a two-fold increased risk for venous thromboembolism (VTE) compared with unaffected individuals [9]. Risk factors for VTE among patients with IBD include active disease, steroid therapy, disease subtype, greater age, and surgery [10,11]. While the cause of VTE among IBD patients is uncertain, underlying mechanisms might be the inflammatory process, fluid depletion, vitamin deficiencies, and prolonged immobilization [12]. Given that IBD patients are at increased risk of VTE, there are concerns that use of combined hormonal contraceptives and depot medroxyprogesterone acetate (DMPA) which are known to increase VTE risk [13–16] might compound the risk.

Patients with IBD might have a higher prevalence of osteoporosis and osteopenia than the general population [17]. The use of DMPA has been associated with small and generally reversible changes in bone mineral density [18] and therefore might be of concern in patients who may have other risk factors for adverse effects on bone health.

IBD is also associated with several hepatobiliary disorders, including primary sclerosing cholangitis [19], a chronic cholestatic liver disease that leads to progressive cirrhosis and ultimately hepatic failure. Since hormonal contraceptives are metabolized by the liver, their use might adversely affect a woman with IBD and whose liver function is severely compromised.

Factors that may impair absorption of OC sex steroids might impact contraceptive effectiveness. These include inflammation and ulceration of the intestinal mucosa, and more rapid transit of gastrointestinal contents in patients who have undergone bowel surgery [20]. Since most absorption of OC steroids occurs in the small bowel [20], OC malabsorption is unlikely to occur among women with only large bowel disease, such as ulcerative colitis, unless surgical treatment in these women involves the small bowel. There are concerns that IBD-related malabsorption might decrease the efficacy of orally-ingested contraceptives [21].

A systematic review published in 2010 identified 10 studies examining contraceptive use among women with IBD and found no increased risk of disease relapse among women with IBD who used OCs compared with women not using OCs, and no differences in the absorption of higher dose combined OCs (COCs) among women with mild ulcerative colitis and small ileal resections compared with healthy women [22]. The current review aims to update the body of evidence on the safety and effectiveness of specific contraceptive methods among women with IBD. The information may be used by guideline development groups that publish evidence-based contraception guidance for clinicians and patients. We focused on two research questions:

We conducted this systemic review according to an a priori protocol, which has been registered in the international prospective register of systematic reviews (PROSPERO) under the registration number CRD42024507789(23) and reported according to Preferred Reporting Items for Systematic Reviews and Meta-analyses [24].

We screened 1,835 unduplicated articles identified from our database search, from which 79 articles were identified for full-text review (Figure 1). Among these articles, 64 were excluded (34 wrong study design, 12 wrong intervention, 7 wrong outcomes, 5 wrong patient population, 4 wrong comparator, and 2 duplicates). Fifteen studies met inclusion criteria [29–43]; seven [30, 31, 33, 39, 41–43] of these were included in the previous systematic review [22] and eight [29, 32, 34–38, 40] were newly identified. Three articles from the previous review did not meet inclusion criteria for this updated review because they were case reports [44–46].

Four studies assessed participants with IBD overall [29, 32, 37, 38], one of which presented results for ulcerative colitis and Crohn’s disease separately [29] and two of which presented multivariable results adjusted for disease type [37, 38]; five studies assessed participants with ulcerative colitis [30, 33, 34, 36, 39], and six studies assessed participants with Crohn’s disease [31, 35, 40–43]. Thirteen articles reported on cohort studies (9 prospective [30–32, 34–36, 40, 42, 43] and 4 retrospective [29, 37, 38, 41]) and 2 reported on pharmacokinetic studies [33, 39]. Of the 13 cohort studies, one assessed hormonal contraceptives as a group [32]; the remaining 10 studies examined OCs [29, 30, 34, 37, 38, 40–43], three of which presented at least some results by OC type (COCs or progestin-only pills [POPs]) [29–31, 34–38, 40–43]. One study also separately examined the progestin IUD [35]. In both pharmacokinetic studies, participants received a single dose of 50 mcg ethinyl estradiol (EE) plus 250 mcg of levonorgestrel (LNG) after an overnight fast [33, 39]. Ten cohort studies assessed the outcome of disease activity or relapse [30–32, 34–36, 40, 41, 43], three cohort studies assessed other adverse health events including VTE and cervical dysplasia [29, 37, 38], and two pharmacokinetic studies assessed changes in contraceptive hormone levels as a proxy for contraceptive effectiveness [33, 39].

This updated systematic review identified eight new studies examining risk of IBD disease activity or relapse or other adverse health outcomes (i.e., VTE, abnormal cervical smears) among women with IBD using contraception. Of the 15 included studies, one cohort study found lower odds of IBD symptoms among hormonal contraceptive users compared with non-hormonal contraceptive users, but higher odds of intestinal inflammation over one year. Nine cohort studies found inconsistent results regarding OC use and ulcerative colitis or Crohn’s disease activity or relapse, with increased and decreased associations for various measures of disease activity or relapse; most were not statistically significant. Two cohort studies found no statistically significant association between OC use and VTE among IBD patients, although confidence intervals were imprecise. One study found no statistically significant association between OC use and abnormal cervical smears. Two pharmacokinetic studies generally suggested no differences in plasma concentrations of steroid hormones after oral ingestion among participants with and without IBD.

Newly identified evidence on IBD disease activity or relapse overall was consistent with evidence included in the previously published systematic review, which concluded no increased risk of disease relapse among women with IBD using OCs [22]. However, the updated evidence base includes two new cohort studies that found significantly increased risk for additional measures of disease activity or relapse comparing OC users with non-users (i.e., number of relapses during follow-up and risk of surgery with longer duration of COC use but not for POP use). The evidence for VTE and abnormal cervical smears is new information. While no association between OC use and abnormal cervical smears was found among women with IBD, we presume that the authors examined the association because some studies have suggested an increased risk of cervical dysplasia among women with IBD [48, 49], and some studies have suggested an increased risk of cervical dysplasia among longer duration OC users [50]. No new evidence was found for contraceptive effectiveness among IBD patients using OCs.

The body of evidence on the safety and effectiveness of contraceptive use among women with IBD has several limitations. Most of the studies were deemed to have high overall risk of bias and the certainty of evidence for all outcomes was rated as very low. Studies that examined VTE had poor generalizability because study populations were not restricted to women of reproductive age. Studies that examined pharmacokinetic outcomes also had poor generalizability because they included small numbers of women with ulcerative colitis, the women had smaller surgical resections limited to the large bowel and findings may not generalize to women with more extensive resections or to women with Crohn’s disease with small bowel inflammation, and the doses of steroid hormones used were higher than most OCs used in the United States presently. Few studies examined adverse health outcomes beyond disease activity or relapse, and only one study examined progestin IUD use among women with IBD. We found no evidence examining risk of osteoporosis or osteopenia among women with IBD using contraception was found, nor studies examining hormonal contraception use among women with IBD and compromised liver function. Last, no studies examined pregnancy as a measure of contraceptive effectiveness comparing women with and without IBD.

In conclusion, this updated review expands upon the previous review with eight newly identified studies. However, evidence is still limited in quantity and quality, with inconsistent findings on risk of disease activity or relapse and lack of high-quality evidence on risk of VTE and contraceptive effectiveness. Further research can focus on these gaps to provide information needed by women with IBD as they make contraceptive choices.