Khalili, H., Higuchi, L. M., Ananthakrishnan, A., Richter, J., Feskanich, D., fuchs, C., & Chan, A. (2013). Oral contraceptives, reproductive factors and risk of inflammatory bowel disease. Gut, 62(8), 1153-1159. https://doi.org/10.1136/gutjnl-2012-302362
Khalili H, Higuchi LM, Ananthakrishnan A, Richter J, Feskanich D, fuchs C, et al. Oral contraceptives, reproductive factors and risk of inflammatory bowel disease. Gut. 2013;62(8):1153-1159. doi:10.1136/gutjnl-2012-302362
Khalili, Hamed, et al. "Oral contraceptives, reproductive factors and risk of inflammatory bowel disease." Gut, vol. 62, no. 8, 2013, pp. 1153-1159.
Oral contraceptive use has been associated with risk of Crohn's disease (CD) and ulcerative colitis (UC).
Objective
To determine whether this association is confounded or modified by other important lifestyle and reproductive factors.
Design
A prospective cohort study was carried out of 117,375 US women enrolled since 1976 in the Nurses Health Study I (NHS I) and 115,077 women enrolled since 1989 in the Nurses' Health Study II (NHS II) with no prior history of UC or CD. These women had provided information every 2 years, on age at menarche, oral contraceptive use, parity, menopause status and other risk factors. Diagnoses of CD and UC were confirmed by review of medical records. Cox proportional hazards models were used to calculate HRs and 95% CIs.
Results
Among 232,452 women with over 5,030,196 person-years of follow-up, 315 cases of CD and 392 cases of UC were recorded through 2007 in NHS II and 2008 in NHS I. Compared with never users of oral contraceptives, the multivariate-adjusted HRs for CD were 2.82 (95% CI 1.65 to 4.82) among current users and 1.39 (95% CI 1.05 to 1.85) among past users. The association between oral contraceptives and UC differed according to smoking history (pheterogeneity=0.04). Age at menarche, age at first birth and parity were not associated with risk of UC or CD.
Conclusion
In two large prospective cohorts of US women, oral contraceptive use was associated with risk of CD. The association between oral contraceptive use and UC was limited to women with a history of smoking.
Hua X et al., 2022·Journal of medical microbiology·Free to read
Introduction. Evidence has linked exogenous and endogenous sex hormones with the human microbiome.Hypothesis/Gap statement. The longitudinal effects of oral contraceptives (OC) on the human gut microbiome have not previously been studied.Aim. We sought to examine the longitudinal impact of OC use on the taxonomic composition and metabolic functions of the gut microbiota and endogenous sex steroid hormones after initiation of OC use.Methodology. We recruited ten healthy women who provided blood and stool samples prior to OC use, 1 month and 6 months after starting OC. We measured serum levels of sex hormones, including estradiol, progesterone, sex hormone-binding globulin (SHBG), and total testosterone. Shotgun metagenomic sequencing was performed on DNA extracted from faecal samples. Species and metabolic pathway abundances were determined using MetaPhlAn2 and HUMAnN2. Multivariate association with linear models was used to identify microbial species and metabolic pathways associated with OC use and endogenous levels of sex hormones.Results. The percentage variance of the microbial community explained by individual factors ranged from 9.9 % for age to 2.7 % for time since initiation of OC use. We observed no changes in the diversity or composition of the gut microbiome following OC initiation. However, the relative abundance of the biosynthesis pathways of peptidoglycan, amino acids (lysine, threonine, methionine, and tryptophan), and the NAD salvage pathway increased after OC initiation. In addition, serum levels of estradiol and SHBG were positively associated with Eubacterium ramulus, a flavonoid-degrading bacterium. Similarly, microbes involving biosynthesis of l-lysine, l-threonine, and l-methionine were significantly associated with lower estradiol, SHBG, and higher levels of total testosterone.Conclusion. Our study provides the first piece of evidence supporting the association between exogenous and endogenous sex hormones and gut microbiome composition and function.
Parker WH et al., 2013·Obstetrics and gynecology·Free full text on PubMed Central
To report long-term mortality after oophorectomy or ovarian conservation at the time of hysterectomy in subgroups of women based on age at the time of surgery, use of estrogen therapy, presence of risk factors for coronary heart disease, and length of follow-up. This was a prospective cohort study of 30,117 Nurses' Health Study participants undergoing hysterectomy for benign disease. Multivariable adjusted hazard ratios for death from coronary heart disease, stroke, breast cancer, epithelial ovarian cancer, lung cancer, colorectal cancer, total cancer, and all causes were determined comparing bilateral oophorectomy (n=16,914) with ovarian conservation (n=13,203). Over 28 years of follow-up, 16.8% of women with hysterectomy and bilateral oophorectomy died from all causes compared with 13.3% of women who had ovarian conservation (hazard ratio 1.13, 95% confidence interval 1.06-1.21). Oophorectomy was associated with a lower risk of death from ovarian cancer (four women with oophorectomy compared with 44 women with ovarian conservation) and, before age 47.5 years, a lower risk of death from breast cancer. However, at no age was oophorectomy associated with a lower risk of other cause-specific or all-cause mortality. For women younger than 50 years at the time of hysterectomy, bilateral oophorectomy was associated with significantly increased mortality in women who had never used estrogen therapy but not in past and current users: assuming a 35-year lifespan after oophorectomy: number needed to harm for all-cause death=8, coronary heart disease death=33, and lung cancer death=50. Bilateral oophorectomy is associated with increased mortality in women aged younger than 50 years who never used estrogen therapy and at no age is oophorectomy associated with increased survival. I.
Systemic lupus erythematosus (SLE) occurs predominantly in women, and hormones may play a role in its etiology. This study was carried out to examine associations between female reproductive and menopausal factors and the development of SLE. A cohort of 238,308 women was prospectively examined. Subjects were older women (ages 30-55 years at start) and younger women (ages 25-42 years at start) from the Nurses' Health Study (NHS) and NHSII cohorts. Incident SLE diagnosed between 1976 and 2003 was confirmed by medical record review. The relative risk (RR) of SLE was estimated separately in each cohort using Cox proportional hazards models, and then pooled using meta-analysis random effects models. Two hundred sixty-two incident cases of SLE were confirmed among the women. In multivariable models adjusted for reproductive and other risk factors, age<or=10 years at menarche (pooled RR 2.1, 95% confidence interval [95% CI] 1.4-3.2), oral contraceptive use (pooled RR 1.5, 95% CI 1.1-2.1), and use of postmenopausal hormones (RR 1.9, 95% CI 1.2-3.1) significantly increased the risk of SLE. An elevation of SLE risk was observed among postmenopausal women primarily after surgical menopause (RR 2.3, 95% CI 1.2-4.5), and also among women with earlier age at natural menopause (P for trend<0.05). Menstrual irregularity was associated with an increased risk of SLE among women in the younger (NHSII) cohort. Age at first birth, parity, and total duration of breastfeeding were not associated with SLE. Early age at menarche, oral contraceptive use, early age at menopause, surgical menopause, and postmenopausal use of hormones were each associated with an increased risk of SLE. These associations may point to the mechanisms underlying the pathogenesis of SLE.
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Gut and Inflammatory Bowel Disease · Inflammatory Bowel Disease
García Rodríguez LA et al., 2005·Aliment Pharmacol Ther
The aetiology of inflammatory bowel disease remains largely unknown. We performed a comprehensive assessment of potential risk factors associated with the occurrence of inflammatory bowel disease. We identified a cohort of patients 20-84 years old between 1995 and 1997 registered in the General Practitioner Research Database in the UK. A total of 444 incident cases of IBD were ascertained and validated with the general practitioner. We performed a nested case-control analysis using all cases and a random sample of 10 000 frequency-matched controls. Incidence rates for ulcerative colitis, Crohn's disease, and indeterminate colitis were 11, 8, and 2 cases per 100 000 person-years, respectively. Among women, we found that long-term users of oral contraceptives were at increased risk of developing UC (OR: 2.35; 95% CI: 0.89-6.22) and CD (OR: 3.15; 95% CI: 1.24-7.99). Similarly, long-term users of HRT had an increased risk of CD (OR: 2.60; 95% CI: 1.04-6.49) but not UC. Current smokers experienced a reduced risk of UC along with an increased risk of CD. Prior appendectomy was associated with a decreased the risk of UC (OR: 0.37; 95% CI: 0.14-1.00). Our results support the hypothesis of an increased risk of inflammatory bowel disease associated with oral contraceptives use and suggest a similar effect of hormone replacement therapy on CD. We also confirmed the effects of smoking and appendectomy on inflammatory bowel disease.
Gut and Inflammatory Bowel Disease · Inflammatory Bowel Disease
Previous epidemiologic studies have suggested a weak association between oral contraceptive use and Crohn's disease, specifically Crohn's colitis. To measure a possible etiologic association, 51 women with Crohn's disease who were 18-50 yr old were studied and compared with peer-nominated ageand sex-matched controls. There were no differences between cases and controls with respect to race, religion, marital status, and number of pregnancies. There was no association between oral contraceptive use and Crohn's disease incidence [current use: odds ratio (OR) 0.73, 95% confidence interval (CI) 0.34-1.59; former use: OR 1.80, CI 0.61-5.29; current or former use: OR 1.00, CI 0.46-2.16]. Stratifying by disease location also failed to identify an association. Cigarette smoking was significantly associated with Crohn's disease incidence. Controlling for possible confounding effects of cigarette smoking did not alter the lack of association between oral contraceptive use and Crohn's disease. Similarly, testing for interaction failed to demonstrate any effect modification. Analyzing for duration of current oral contraceptive use or time interval since last use failed to demonstrate a "dose-response" effect. The study was of sufficient size to detect statistical significance for oral contraceptive use for odds ratios of greater than or equal to 2.76. From this community-based matched case-control study, there was no association between oral contraceptive use and Crohn's disease, and women need not be advised to discontinue oral contraceptive use when a diagnosis of Crohn's disease is made.
Gut and Inflammatory Bowel Disease · Inflammatory Bowel Disease
Pasvol TJ et al., 2022·Alimentary pharmacology & therapeutics·Free full text on PubMed Central
How contraceptive formulation, dose, duration of therapy and mode of delivery affects the risk of inflammatory bowel disease (IBD) is poorly described. To examine associations between types of hormonal contraception and development of IBD. This was a nested case-control study using IQVIA Medical Research Data. Women aged 15-49 years with a new diagnosis of IBD were matched with up to six controls by age, practice and year. Odds ratios (OR) and 95% confidence intervals (95% CI) for incident IBD and use of contraception were calculated. 4932 incident cases of IBD were matched to 29 340 controls. Use of combined oral contraceptive pills (COCPs) was associated with the development of Crohn's disease and ulcerative colitis (OR 1.60 [1.41-1.82] and 1.30 [1.15-1.45], respectively). Each additional month of COCP exposure per year of follow-up increased risk of Crohn's disease by 6.4% (5.1%-7.7%) and ulcerative colitis by 3.3% (2.1%-4.4%). Progestogen-only pills had no effect on Crohn's disease risk (OR 1.09 [0.84-1.40]) but there was a modest association with ulcerative colitis (OR 1.35 [1.12-1.64]). Parenteral contraception was not associated with the development of Crohn's disease or ulcerative colitis (OR 1.15 [0.99-1.47] and 1.17 [0.98-1.39], respectively). We observed an increase in the risk of IBD with increasing duration of exposure to COCPs. Progestogen-only pills were not associated with Crohn's disease but there was a modest association with ulcerative colitis. There was no association between parenteral progestogen-only contraception and IBD. These findings are broadly consistent with a hypothesis that the oestrogen component of contraception may drive IBD pathogenesis.
Gut and Inflammatory Bowel Disease · Inflammatory Bowel Disease
Vessey M et al., 1986·Br Med J (Clin Res Ed)·Free full text on PubMed Central
Since the start in 1968 of the Oxford Family Planning Association contraceptive study 31 women have developed ulcerative colitis and 18 have developed Crohn's disease, giving incidences of 0.15 and 0.09/1000 woman years respectively. The incidence of ulcerative colitis in women who were non-smokers on entry to the study was 0.17/1000 woman years and the incidence in smokers was 0.11/1000 woman years. The findings for Crohn's disease were entirely different, the corresponding incidences being 0.05 and 0.17/1000 woman years respectively. Both ulcerative colitis and Crohn's disease were more common among women currently using oral contraceptives than among those not doing so. Incidences per 1000 woman years for ulcerative colitis were 0.26 in users and 0.11 in non-users; for Crohn's disease the incidences were 0.13 and 0.07 respectively. Though the association between the use of oral contraceptives and chronic inflammatory bowel disease cannot be regarded as established, the effects of smoking have been shown consistently in many studies. This observation provides an important clue to the aetiology of chronic inflammatory bowel disease.
Autoimmune and Inflammatory Disease › Gut and Inflammatory Bowel Disease › Inflammatory Bowel Disease · Contraception › Oral Contraceptives › Autoimmune Disease Risk
Hamed Khalili, Ashwin N Ananthakrishnan, James M Richter, Diane Feskanich, Charles S Fuchs, Andrew T Chan, Leslie M Higuchi
H Khalili, A Ananthakrishnan, Jim Richter, Jimmy Richter, J Richter, D Feskanich, Charlie Fuchs, Chuck Fuchs, C Fuchs, Andy Chan, Drew Chan, A Chan, L Higuchi
PMID 22619368 22619368 DOI 10.1136/gutjnl-2012-302362 10.1136/gutjnl-2012-302362 Khalili et al. 2012, Khalili 2012
Cite this article
Khalili, H., Higuchi, L. M., Ananthakrishnan, A., Richter, J., Feskanich, D., fuchs, C., & Chan, A. (2013). Oral contraceptives, reproductive factors and risk of inflammatory bowel disease. Gut, 62(8), 1153-1159. https://doi.org/10.1136/gutjnl-2012-302362
Khalili H, Higuchi LM, Ananthakrishnan A, Richter J, Feskanich D, fuchs C, et al. Oral contraceptives, reproductive factors and risk of inflammatory bowel disease. Gut. 2013;62(8):1153-1159. doi:10.1136/gutjnl-2012-302362
Khalili, Hamed, et al. "Oral contraceptives, reproductive factors and risk of inflammatory bowel disease." Gut, vol. 62, no. 8, 2013, pp. 1153-1159.
