Opinions differ regarding the association between gallbladder disease and oral contraceptive (OCs). The objective of this paper is to quantify cholecystectomy rate among women initiating OCs

Heartwell, Stephen F.

Stuart, Gretchen S.

Tang, Jennifer H.

Westhoff, Carolyn L.

PubMed

Carolina Digital Repository

A high cholecystectomy rate in a cohort of women who areMexican-American, and postpartum, at the time of oralcontraceptive pill initiationGretchen S. Stuarta,*, Jennifer H. Tangb, Stephen F. Heartwellc, Carolyn L. Westhoffd, andthe QuickStart Study Groupa Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill, Chapel Hill, NC27599-7030, USAb Department of Obstetrics and Gynecology, Brigham and Women’s Hospital, Boston, MA 02115, USAc Susan Thompson Buffett Foundation, Omaha, NE 68131, USAd Department of Obstetrics and Gynecology, Columbia University, NY 10032AbstractBackground—Opinions differ regarding the association between gallbladder disease and oralcontraceptive (OCs). The objective of this paper is to quantify cholecystectomy rate among womeninitiating OCs.Study Design—Women under age 25 years were enrolled at four sites in a randomized trialevaluating initiation of OCs. Hospitalizations while enrolled were elicited during follow-upinterviews, and medical records of women who underwent cholecystectomy were reviewed.Results—Eight of 757 women enrolled at University of Texas Southwestern Medical Center(UTSW) underwent cholecystectomy, a rate of 25.3/1000 woman-years (95% CI 8.1, 42.5). All eightwere Mexican-American and postpartum when they initiated OCs. The expected rate is 4.2/1000woman-years for US women aged 15–44.Conclusions—Women enrolled at the UTSW site had an increased rate of cholecystectomy, andwere more likely to be postpartum and Mexican-American than women enrolled at the other sites.KeywordsOral contraceptives; Mexican-American; postpartum; cholecystectomy; cholelithiasis; gallstones1. IntroductionConflicting opinions prevail regarding the association of gallbladder disease with the use ofOCs. This is important because OCs are the most common form of reversible contraceptionused in the United States [1], and recently the reported annual cholecystectomy rate for womenages 15–44 was 4.2/1000 [2], a frequent operation in the U.S. A recent randomized clinicaltrial evaluating oral contraceptive initiation provided us the opportunity to analyze*Corresponding author: Gretchen S. Stuart, 130 Mason Farm Rd, Ste 2102, CB #7030 Chapel Hill, NC 27599-7030, Phone: (919)843-7852, Fax: (919) 966-6001, gstuart@med.unc.edu.Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customerswe are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resultingproof before it is published in its final citable form. Please note that during the production process errors may be discovered which couldaffect the content, and all legaldisclaimers that apply to the journal pertain.NIH Public AccessAuthor ManuscriptContraception. Author manuscript; available in PMC 2008 November 1.Published in final edited form as:Contraception. 2007 November ; 76(5): 357–359.NIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author Manuscriptcholecystectomy rates among women initiating oral contraceptives [3]. The objective of thispaper is to quantify cholecystectomy rate among women initiating OCs.2. Materials and methods2.1 Study designThis multicenter randomized trial was conducted between March 2003 and February 2005 atthree University centers: Emory University, Atlanta; Mt. Sinai Medical Center, New York;and the University of Texas Southwestern Medical Center, Dallas (UTSW). Recruitment tookplace in their Family Planning and Teen Clinics. These clinics serve predominantly Latina andAfrican-American populations; they are funded in part by Title X and by other federal and stategrants.Clinical Center Institutional Review Boards and the Columbia University (coordinating center)Institutional Review Board reviewed and approved the study. The study intervention wasrandom assignment to immediate initiation of the OC at the time of study enrollment (quickstart, intervention group) or conventional initiation of the OC with the next menstrual period(conventional start, control group). The results of the intervention and further details regardingstudy methods are reported elsewhere [3].Young women requesting oral contraceptives were the target population for recruitment in thisstudy. After the completion of clinical care following routine local protocols, health careproviders referred women aged less than 25 years requesting OCs to study staff for screening.We excluded women with medical contraindications to oral contraceptives and women withlactational amenorrhea (because we could not reasonably instruct them to wait for the nextmenses to begin using OCs). In Texas, at the request of the local IRB, we excluded postpartumor post-abortion women younger than 18 years of age.Subjects participated in three- and six-month telephone interviews to assess OC continuation,pregnancy since date of last interview, sexual activity (i.e., risk of pregnancy), and adverseevents. We obtained medical records to validate all reported serious adverse events includinghospitalizations. Medical records for the cholecystectomy admission and any antecedentpregnancy of the women who underwent cholecystectomy were reviewed in detail andpertinent data were abstracted. All gallbladder specimens were confirmed to have cholelithiasison pathology reports.2.1 Statistical analysisData collected for the QuickStart study was entered and maintained by the study statisticalcoordinating center at Columbia University.Analysis included chi-square, Student’s t-test, and Fisher’s exact test. Rate and standard errorof proportions were calculated for the UTSW cholecystectomy rate.3. ResultsSeven hundred fifty-seven women were enrolled at the UTSW site during the study period.Six hundred eighty-three (90.2%) completed the three-month follow-up interview and 633(83.6%) completed the study by undergoing the six-month interview, resulting in 316.5woman-years at the University of Texas. Eight women at the UTSW site reported undergoinga cholecystectomy. The two other clinical centers enrolled a total of 959 subjects; none of thosewomen reported undergoing a cholecystectomy. BMI was similar at all the sites, and theaverage age of women at UTSW was 20.9 ± 2.1 years compared with 19 ± 2.7 years at theother two sites (p<0.01).Stuart et al. Page 2Contraception. Author manuscript; available in PMC 2008 November 1.NIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author ManuscriptAt UTSW the women were more likely to be postpartum and of Mexican-American ethnicitythan the women enrolled at the other sites. Six hundred women enrolled at UTSW identifiedthemselves as Hispanic ethnicity (87.3%), 91% of whom called themselves Mexican-American, compared to 347 (36.2%) at the other two sites (p<0.01) reporting Hispanicethnicity. Five hundred women (66.1%) enrolled at UTSW were postpartum when theyinitiated their oral contraceptives, compared to only 36 (3.8%) at the other two sites (p<0.01).Eight women at UTSW reported undergoing cholecystectomy for symptomatic cholecystitisduring the study follow-up period. All eight women were postpartum and of Mexican-American ethnicity (Table 1).The cholecystectomy rate at UTSW was 25.3/1000 woman-years (95% CI 8.1/1000,42.5/1000), compared to the expected rate in the United States of 4.2/1000 woman-years yieldsa rate ratio of 6.0 (95% CI 1.92, 10.11).4. DiscussionCholelithiasis requiring cholecystectomy was reported only at the UTSW Medical Center site,and all eight of those women were Mexican-American, and were postpartum at the time of OCinitiation. There are numerous reports which provide conflicting conclusions regarding the riskof cholelithiasis and cholecystectomy when taking OCs [4–21], but none included women whowere specifically postpartum. At least three studies have reported on an increased associationof gallbladder disease and oral contraceptive use only during the first few years of OC use,suggesting that OC use may accelerate the course of pre-existing gallstone disease [10,23,24].The relationship between Hispanic ethnicity (specifically Mexican-Americans) and gallstones(as diagnosed by ultrasound) was reported in the NHANES III survey [25]. Among women,age-adjusted prevalence of gallstones was highest in Mexican-Americans (26.7%), followedby non-Hispanic whites (16.6%) and non-Hispanic blacks (13.9%). A chart review of aprimarily Mexican-American outpatient population in San Antonio, found the prevalence ofgallstone disease to be highest in the Mexican-American ethnic group [23]. Neither of thesestudies reported on postpartum women.This study provides no information about symptoms suggestive of cholelithiasis in the entirestudy population. Our report includes only women who underwent cholecystectomy within 6months of OC initiation. We have no information on women with cholelithiasis withouthospitalization or women who had a later cholecystectomy.At this hospital post-partum Mexican-American women had an increased risk ofcholecystectomy after OC initiation compared to other women in the study. This was roughlysix times the national rate for this age group [2]. While clinical decision-making at UTSW mayhave favored cholecystectomy compared to other study locations, an increased risk of thismagnitude is unlikely to be due to clinical judgment alone. In addition all surgical cases werefound to have cholelithiasis. Thus, this difference is likely real and clinically important.AcknowledgementsThis work was supported by the National Institutes of Health Grant 1RO1-HD42413. Dr. Stuart is supported by 5K12HD050113 (Women’s Reproductive Health Research Faculty Scholar Award).Stuart et al. Page 3Contraception. Author manuscript; available in PMC 2008 November 1.NIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author ManuscriptReferences1. Abma J, Chandra A, Mosher W, Peterson L, Piccinino L. Fertility, family planning and women’s health:New data from the 1995 National Survey of Family. National Center for Health Statistics. Vital HealthStat 1997;23(19)2. Freid, VM.; Prager, K.; MacKay, AP.; Xia, H. Health, United States, 2003 – 2005. Hyattsville, MD:National Center for Health Statistics; 2003. Chartbook on trends in the Health of Americans.3. Westhoff C, Heartwell S, Edwards S, et al. Initiation of oral contraceptives using a quick start comparedwith a conventional start: A randomized controlled trial. Obstet Gynecol 2007;109:1270–6. [PubMed:17540797]4. Devesa F, Ferrando J, Caldentey M, et al. Cholelithiasic disease and associated factors in a Spanishpopulation. Dig Dis Sci 2001;46:1424–36. [PubMed: 11478494]5. Jorgensen T. 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Author manuscript; available in PMC 2008 November 1.NIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author ManuscriptStuart et al. Page 6Table 1Characteristics of the eight women who underwent cholecystectomy at UTSW compared to the remainder of thecohort at UTSW which did not undergo cholecystectomyCholecystectomy (n =8)N (%)No cholecystectomy(n =749)N (%)pPostpartum 8 (100) 492 (66) .06Mexican-American 8 (100) 590 (79) .20Contraception. Author manuscript; available in PMC 2008 November 1.

A high cholecystectomy rate in a cohort of Mexican American women who are postpartum at the time of oral contraceptive pill initiation

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A high cholecystectomy rate in a cohort of Mexican American women who are postpartum at the time of oral contraceptive pill initiation

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