REVIEW

CLINICIANS CORNER

Sexual Abuse and Lifetime Diagnosis of Somatic Disorders

A Systematic Review and Meta-analysis
Molly L. Paras, BS Mohammad Hassan Murad, MD Laura P. Chen, BS Erin N. Goranson, BS Amelia L. Sattler, BS Kristina M. Colbenson, BS Mohamed B. Elamin, MBBS Richard J. Seime, PhD Larry J. Prokop, MLS Ali Zirakzadeh, MD general medical care have a history of sexual abuse. In the United States, national population surveys have found the annual incidence of sexual violence to be 2.5% for women and 0.9% for men.1 Additionally, it is estimated that 1 in 15 adults has experienced forced sexual intercourse.1 Retrospective studies have also demonstrated a high prevalence of adult survivors of childhood sexual abuse: 16% of men and 25% of women in the United States.2 Estimates of the prevalence of rape range from 7%-21% for adults and 5%-17% for children.3-7 These statistics are likely underestimates because the event is frequently underreported.8,9 To date, research on the long-term effects of sexual abuse has primarily focused on mental health outcomes. Strong evidence supports a link between childhood sexual abuse and mulCME available online at www.jamaarchivescme.com and questions on p 579.
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Context Many patients presenting for general medical care have a history of sexual abuse. The literature suggests an association between a history of sexual abuse and somatic sequelae. Objective To systematically assess the association between sexual abuse and a lifetime diagnosis of somatic disorders. Data Sources and Extraction A systematic literature search of electronic databases from January 1980 to December 2008. Pairs of reviewers extracted descriptive, quality, and outcome data from included studies. Odds ratios (ORs) and 95% confidence intervals (CIs) were pooled across studies by using the random-effects model. The I2 statistic was used to assess heterogeneity. Study Selection Eligible studies were longitudinal (case-control and cohort) and reported somatic outcomes in persons with and without history of sexual abuse. Results The search identified 23 eligible studies describing 4640 subjects. There was a significant association between a history of sexual abuse and lifetime diagnosis of functional gastrointestinal disorders (OR, 2.43; 95% CI, 1.36-4.31; I2 =82%; 5 studies), nonspecific chronic pain (OR, 2.20; 95% CI, 1.54-3.15; 1 study), psychogenic seizures (OR, 2.96; 95% CI, 1.12-4.69, I2 =0%; 3 studies), and chronic pelvic pain (OR, 2.73; 95% CI, 1.73-4.30, I2 =40%; 10 studies). There was no statistically significant association between sexual abuse and a lifetime diagnosis of fibromyalgia (OR, 1.61; 95% CI, 0.853.07, I2 =0%; 4 studies), obesity (OR, 1.47; 95% CI, 0.88-2.46; I2 =71%; 2 studies), or headache (OR, 1.49; 95% CI, 0.96-2.31; 1 study). We found no studies that assessed syncope. When analysis was restricted to studies in which sexual abuse was defined as rape, significant associations were observed between rape and a lifetime diagnosis of fibromyalgia (OR, 3.35; 95% CI, 1.51-7.46), chronic pelvic pain (OR, 3.27; 95% CI, 1.0210.53), and functional gastrointestinal disorders (OR, 4.01; 95% CI, 1.88-8.57). Conclusion Evidence suggests a history of sexual abuse is associated with lifetime diagnosis of multiple somatic disorders.
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ANY PATIENTS SEEN FOR

tiple psychiatric sequelae.10,11 However, studies investigating the association between sexual abuse and somatic outcomes have been less definitive. Initial inquiries date back to the late 1970s, when the link between sexual abuse and hysterical seizures was investigated.12 Additional studies evaluating the association of sexual abuse with chronic pelvic pain13,14 and chronic pain15,16 followed in the 1980s. Over time, disorders including fibromyalgia,17-19 func-

tional gastrointestinal disorders,5,20,21 and obesity21 have been assessed for their association with sexual abuse.
Author Affiliations: Mayo Clinic College of Medicine (Mss Paras, Chen, Goranson, Sattler, and Colbenson); Division of Preventive Medicine (Dr Murad) and Knowledge and Encounter Research Unit (Drs Murad and Elamin); Department of Psychiatry and Psychology (Dr Seime); Mayo Clinic Libraries (Mr Prokop); and Department of General Internal Medicine (Dr Zirakzadeh), Mayo Clinic, Rochester, Minnesota. Corresponding Author: Ali Zirakzadeh, MD, Mayo Clinic Department of General Internal Medicine, 200 First St SW, Rochester, MN 55906 (zirakzadeh.ali @mayo.edu).

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SEXUAL ABUSE AND SOMATIC DISORDERS

Epidemiologic studies demonstrate that such disorders are commonly encountered by physicians across a broad spectrum of medical practice. Fibromyalgia occurs in approximately 5% of patients seen in general practices.22,23 Functional gastrointestinal disorders are also highly prevalent, with estimates of 5% to 25% for irritable bowel syndrome in the general population.24,25 As such, physicians are commonly faced with the diagnosis and management of these disorders. Although several studies have attempted to investigate associations between patient history of sexual abuse and development of somatic disorders, to our knowledge no systematic review has been performed to evaluate the strength of these associations. The objective of this study was to systematically assess and summarize the available evidence regarding the association between a history of sexual abuse and lifetime diagnosis of somatic disorders. METHODS The protocol for this systematic review was developed and executed by physicians and researchers in the disciplines of internal medicine, preventive medicine, epidemiology, statistics, and psychology. The methods described by the Cochrane Collaboration were used in the development of the protocol.26 The reporting of results was based on the recommendations of the Meta-analysis of Observational Studies in Epidemiology group.27
Data Sources and Search Strategies

designed and performed by an experienced librarian (L.J.P.), with input from the studys principal investigator. Controlled vocabulary supplemented with keywords was used to define the concept areas, sexual abuse, and physical/psychological disorders, as well as to limit epidemiologic studies. The complete strategy is available on request from the author.
Study Selection

pain syndrome, and chronic pelvic pain syndrome. Eligible studies contained an outcome and a nonoutcome group, designated by self-report or clinical identification.
Data Extraction

A comprehensive search of several databases (from January 1980 to December 2008, all age groups, any language, any population), including MEDLINE, EMBASE, CINAHL, Current Contents, PsycINFO, American College of Physicians Journal Club, Cochrane Controlled Trials Registry, Cochrane Database of Systematic Reviews, and Database of Abstracts and Reviews of Effectiveness, was conducted. The search strategy was

Eligible studies were longitudinal casecontrol and cohort studies. Studies were included regardless of publication status, sample size, length of follow-up, or language of publication. Sexual abuse was categorized into 2 major groups: rape and all forms of sexual abuse. Rape was defined as penetration with a body part or foreign object (intravaginal or anal).28 All forms of sexual abuse was designed to be broad to capture the wide variety of definitions used to characterize sexual violence. These other forms included, but were not limited to, noncontact exposure of genitals, threatening sexual violence, and contact involving genitals and mouth.28 If a study did not specify that the form of sexual abuse was rape, then it was classified as all forms of sexual abuse. For studies in which abuse was not further specified, authors were contacted to provide data for that subset of patients with a history of sexual abuse. If studies included data for sexually abused, nonabused, and physically abused individuals, the latter groups were pooled as controls. This practice was adopted to reduce the confounding effect of physical abuse on the outcome as studies have shown childhood physical abuse prevalence rates ranging between 3.8% and 20.6% in the general population.29-31 As per protocol, the outcomes investigated in this study were functional gastrointestinal disorders, chronic headache, psychogenic seizure disorder (also called nonepileptic seizure or pseudoseizure), non-neurocardiogenic syncope, fibromyalgia, obesity, chronic

Teams of reviewers (M.L.P., L.P.C., E.N.G., A.L.S., K.M.C., A.Z.) working independently and in pairs analyzed eligible titles, abstracts, and full-text articles. Data from included studies were extracted in duplicate. Articles in foreign languages (Chinese [1], Czech [1], French [10], German [18], Hungarian [1], Italian [4], Spanish [8], and Turkish [2]) were translated or the author was contacted when available to provide required information. A description of the type of study and its participants was obtained, including mean age of subjects, sex, and race. If greater than 70% of the study population was of one race, then the study was designated as evaluating that race predominantly. If not further specified, research studies based in Scandinavian countries were assumed to enroll predominantly white participants. The type of sexual abuse (either rape or all forms of sexual abuse) was recorded, along with the age at the abuse. Childhood abuse was defined as abuse occurring at or before age 18 years. Raw data for the exposed, nonexposed, outcome, and nonoutcome groups were obtained when possible. If numbers were not available, then odds ratios (ORs) were recorded, with preference given to adjusted ORs. Authors of eligible articles not presenting raw data or ORs were contacted by e-mail or letters. Authors were requested to provide data required for the analysis that were not printed in the published article.
Quality Assessment

The quality of each eligible study was assessed in duplicate. Disagreements were resolved by mediation, with input from the principal investigator. The Newcastle-Ottawa Quality Assessment Scale was used for case-control studies and cohort studies.32 This scale
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SEXUAL ABUSE AND SOMATIC DISORDERS Subgroup and Sensitivity Analyses

Figure 1. Study Selection Process

4202 Articles identified through literature search

1500 Articles excluded 1442 Excluded based on initial abstract review 58 Unable to obtain full manuscript with potential somatic outcomes

2702 Original articles reviewed

2679 Articles excluded 1884 Not relevant, not original research, or single-arm studies 728 Had no somatic outcomes 22 Were cross-sectional study design 45 Somatic data not available from author

23 Articles included in analysis

The literature review included search for articles with psychiatric outcomes reported elsewhere.

consists of 8 questions, with a maximum of 10 possible points for each type of study.
Statistical Analysis

A priori hypotheses were formed to explore subgroup interactions and explain inconsistency in the direction and magnitude of associations among studies. These included study design (cohort design vs case-control design), the age at which sexual abuse took place (childhood vs adult), sex of the abused person, and race of the abused subject. To test the hypotheses of a subgroup effect, a test of interaction with a predetermined 2-tailed of .05 was used.36 Meta-regression was used to assess whether study quality affects the strength of reported associations. In the regression model, the natural logarithm of the OR represents the dependent variable and the quality score represents the independent variable. A sensitivity analysis was planned to determine whether the type of abuse (rape vs all forms of sexual abuse) affects study conclusions.
Publication Bias

Odds ratios were pooled for dichotomous outcomes from each study with the DerSimonian-Laird randomeffects model. The 95% confidence interval (CI) for each outcome was estimated to reflect the uncertainty of point estimates.33 An OR of 1.0 indicates no association and OR greater than 1.0 indicates increased risk for the referenced outcome. The I2 statistic was used to estimate the percentage of total variation across studies because of heterogeneity, rather than chance (ie, the percentage of variability of associations across studies that is not due to chance or random error, but rather due to real differences in study patients, design, or outcome definitions).34 I2 values of less than or equal to 25%, 50%, and greater than or equal to 75% represent low, moderate, and high inconsistency, respectively. Statistical analysis was conducted with Comprehensive MetaAnalysis, version 2 (Englewood, New Jersey). P .05 was set as the threshold for significance.35
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To assess the potential effect of publication bias, we planned to inspect funnel plots for asymmetry and use the Duval and Tweedie trim and fill method37 and the Begg and Mazumdar rank correlation test.38 RESULTS A total of 23 studies met the inclusion criteria and provided data for 4640 subjects (FIGURE 1). Nineteen of the included studies were case-control design (2778 individuals) and 4 were cohort design (1862 individuals). Sixteen included only female subjects and the remainder evaluated both sexes. Four investigated populations composed of a majority of white subjects, whereas the remaining sample populations were mixed or not specified in terms of race. A total of 11 studies took place in nations outside of the United States. No foreign-language study met inclusion criteria, and no unpublished study met eligibility criteria. Seven of the studies investigated sexual abuse occurring only in childhood. None of the studies examined abuse only in adulthood. Seven in-

cluded data for both childhood and adulthood abuse. The remaining studies did not specify the age at which abuse occurred. The included casecontrol studies ascertained sexual abuse exposure by using self-reporting in questionnaires (11 studies) and interviews (8 studies). Cohort studies confirmed histories of sexual abuse by using legal documentation (3 studies) and interviews (1 study). Four studies provided data for individuals who had experienced rape. The remaining studies collected data from persons who reported exposure to all forms of sexual abuse. Nineteen of the 23 studies provided definitions used to assess sexual abuse. These included the following: threatening sexual attacks, sexual coercion, unwanted exposure of perpetrators genitalia, unwanted touching of abused individuals genitals or other sexual parts, and unwanted or forced touching of perpetrators genitals or other sexual parts. The details of the baseline characteristics of each study are listed in TABLE 1. Each study was assessed for quality according to the population and sampling methods, description of exposure and outcomes, and statistical adjustment of the data (T ABLE 2 and TABLE 3). Only 5 of 23 studies matched abuse survivors and controls by 2 factors or adjusted for 2 or more confounders simultaneously in their multiple regression models. Among casecontrol studies, only 13 of 19 studies obtained controls from the same population as cases. Furthermore, only 10 of 19 case-control studies were considered to use rigorous selection criteria of cases (during defined period, throughout defined area, all cases or random/consecutive cases in a defined group).
Meta-analyses

There was a significant association between a history of sexual abuse and a lifetime diagnosis of functional gastrointestinal disorders (OR, 2.43; 95% CI, 1.36-4.31; I2 =82%; 5 studies), nonspecific chronic pain (OR, 2.20; 95% CI,

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Table 1. Studies Included in Meta-analysis

Source No. of Participants and Setting Age Sex (SD or Range), y a F 50 (19-70) Race b Not specified Study Definition of Abuse c Age at Abuse d Method of Abuse Ascertainment Outcome and Definition e

Case-control studies Boisset-Pioro 244 Consecutive et al,19 1995 fibromyalgia and rheumatology control patients from private rheumatology clinics in Canada Ciccone et al,39 2005 105 Women with fibromyalgia and controls

Sexual exposure or NS/NR threatening, sexual touching, attempts of sex, or completed sex

National Population Previous diagnosis Survey of Canada; of fibromyalgia patient completed paper questionnaire in private room Structured telephone Fibromyalgia interview by diagnosed by female researcher standard tender point examination for fibromyalgia Anonymous, confidential, self-report questionnaire Chronic pelvic pain diagnosed by gynecologist

50.5

Majority white

Touching of sexual NS/NR parts, sexual intercourse, or other unwanted sexual experience According to Sexual Life Events Inventory NS/NR

Collett et al,40 1998

90 UK women with chronic pelvic pain, pain in a different location, or pain free 703 Patients with IBS from university hospitals in France and controls without functional GI disorders 60 Patients with nonepileptic seizure disorder and controls with generalized tonic-clonic seizures in India 51 Patients with nonepileptic seizures and controls with epilepsy treated at a university hospital 40 Women referred to gynecologic department of general hospital in Germany for diagnostic laparoscopy

16-50

Majority white

Delvaux et al,41 1997

Both

41 (19)

Not specified

Verbal sexual abuse, sexual exhibitionism, sexual harassment, touch, rape

NS/NR

Anonymous, confidential self-report questionnaire

Functional GI disorders based on the Rome Criteria for IBS

Dhanaraj et al,42 1997

30 (17-45)

Not specified

Not defined

NS/NR

Discussion with physician to identify stressful life events (history of sexual abuse)nonstructured

Psychogenic seizures diagnosed by the criteria established from Neurology 1999

Dikel et al,43 2003

Both

36 (11.8)

Not specified

Physical contact Childhood between anogenital region or breast

Patient completed Psychogenic questionnaire seizures before meeting diagnosed by with psychologist neurologist

Ehlert et al,44 1999

29

Not specified

Abuse ranging from NS/NR involuntary sexual contact to intercourse (anal/vaginal/oral)

Patient completed questionnaire

Chronic noncyclic pelvic pain 4 mo with medical examination, laboratory studies, hysteroscopy, and laparoscopy Obesity as defined by the Heavy Frame Metropolitan Ideal Body Weight

Felitti et al,45 1993

200 Obese persons applying to a weight loss program and nonobese controls from the general population 30 Women with chronic pelvic pain without organic pathology and infertile, pain-free controls from gynecologic department of German hospital 307 Persons from Australia with IBS and controls with abdominal pain

Both

41

Not specified

Not defined

Childhood

Self-reported

Heim et al,46 1998

29 (6.1)

Not specified

Abuse ranging from NS/NR involuntary sexual contact to intercourse (anal/vaginal/oral)

Structured interview Chronic noncyclic with psychologist pelvic pain on day of 4 mo admission

Koloski et al,47 2005

Both

46

Not specified

Sexual exposure, threatening, touch, attempts to have sex, completed sex

Both

National Population Functional GI Survey of Canada, disorders based self-report on the Rome Criteria for IBS

(continued)

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Table 1. Studies Included in Meta-analysis (continued)

Source No. of Participants and Setting Age Sex (SD or Range), y a F 34 (9.6) Race b Not specified Study Definition of Abuse c Age at Abuse d Method of Abuse Ascertainment Outcome and Definition e

Case-control studies Lampe et al,48 79 Outpatients at 2000 the department of gynecology for pelvic pain, orthopedics for back pain, and pain-free persons in Austria Lampe et al,49 2003 105 Patients with chronic lower back pain, chronic pelvic pain, and pain-free persons in Austria 205 Women with chronic pelvic pain, chronic pain in other locations, and controls without pain

Breasts, oral, vaginal, Childhood anal touching, fondling, penetration

Semi-structured Chronic pelvic pain interview with 6 mo with woman trained in evaluation using psychodynamics ultrasonography, laparoscopy

35 (9.7)

Not specified

Breasts, oral, vaginal, Childhood anal touching, fondling, penetration

Semi-structured Chronic pelvic pain interview with 6 mo with woman trained in evaluation using psychodynamics ultrasonography, laparoscopy

Rapkin et al,50 1990

40 (13.8)

Majority white

Sexual contact 17 y or involuntary sexual contact 17 y

Both

Self-report questionnaire

Chronic pelvic pain defined with a pain questionnaire, and disabling pain 6 mo, with previous laparoscopy Chronic noncyclic pelvic pain 6 mo

Reinhard,51 2004

99 Women with chronic pelvic pain

29 (6.9)

Not specified

Incest (coitus with Both legal relative), repetitive sexual molestation (noncoital touching/ exposure), penetration (vaginal/oral/anal) Threatened sexual Both events, sexual touch, forced sex

Self-report questionnaire

Salmon et al,52 2003

162 Nonepileptic Both seizure patients referred to neurologists in United Kingdom and control group without seizures 82 Women with fibromyalgia and controls without major medical conditions 47 Persons with IBS or inflammatory bowel disease F

35

Not specified

Self-reported questionnaire

Psychogenic seizures as diagnosed by a neurologist

Taylor et al,17 1995

43 (11.2)

Majority white

Sexual exposure, NS/NR threatened sexual experience, sexual touch, forced sex Sexual attempts, penetration, fondling NS/NR

Self-reported confidential questionnaire

Fibromyalgia based on the American College of Rheumatology 1990 criteria Functional GI disorders with diagnosis of IBS confirmed by gastroenterologist Chronic medically unexplained pelvic pain 6 mo

Walker et al,5 1993

Both

36 (13.4)

Not specified

Structured interview

Walker et al,53 1995

100 Women scheduled for laparoscopy with chronic pelvic pain or controls (no pain) 69 Women with fibromyalgia and controls with rheumatoid arthritis

31 (7)

Not specified

Sexual attempts, penetration, fondling

Both

Structured interview

Walker et al,54 1997

NS/NR

Not specified

Forced, threatened, Both taken advantage of by vaginal/anal/oral intercourse

Structured interview

Fibromyalgia as defined by the American College of Rheumatology 1990 criteria Obesity defined as BMI 30 or 95th percentile

Cohort studies Noll et al,55 2007 173 Sexually abused females referred by child protective services in Washington, DC, area and comparison females recruited via advertisements F 6-16 Mixed Sexual contact, penetration by family member Childhood Children with documented sexual abuse referred to child protective services

(continued)

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Table 1. Studies Included in Meta-analysis (continued)

Source Cohort studies Raphael et al,56 2001 1196 Abused and Both neglected children matched with controls from Midwest 29 (3.9) Mixed Assault and battery Childhood with intent to gratify sexual desires, fondling, touching, sodomy, rape, incest Not defined Childhood Sexual abuse documented in court/legal records Chronic nonspecific pain diagnosed using somatization module of Diagnostic Interview Schedule III-R No. of Participants and Setting Age Sex (SD or Range), y a Race b Study Definition of Abuse c Age at Abuse d Method of Abuse Ascertainment Outcome and Definition e

Rimsza et al,16 1988

139 Children and adolescents at a public hospital with sexual abuse history and controls from general clinic

10 (2-17)

Not specified

Patients had received Functional GI medical care disorders, sleep for the sexual disorders, with violence episode no further and medical specification records contain regarding data on sexual criteria used to violence determine outcome Semi-structured Self-reported interview with chronic pelvic female researcher pain, functional (psychiatrists and GI disorders, social workers) headache

Romans et al,57 2002

354 Random community sample of New Zealand women

47 (12.5)

Not specified

Noncontact, sexual Both abuse, nongenital sexual contact, sexual touching, attempted/ completed intercourse

Abbreviations: BMI, body mass index; GI, gastrointestinal; IBS, irritable bowel syndrome; NS/NR, not specified/not reported. a Mean age unless otherwise specified. b Majority of race defined as greater than 70% of population; assumption made for Scandinavian countries that population was greater than 70% white; mixed designates population where no race was greater than 70%. c Rape defined as forced vaginal, anal, or oral penetration; any abuse defined as all forms of sexual abuse, including rape. d Data on age when abuse occurred. Childhood defined as 18 years or younger. Both designates studies for which data were extracted on childhood and adult abuse separately. e Definition of outcome is the means by which the study labeled individuals as having the outcome.

1.54-3.15; I2 = not available; 1 study), psychogenic seizures (OR, 2.96; 95% CI, 1.12-4.69; I2 = 0%; 3 studies), and chronic pelvic pain (OR, 2.73; 95% CI, 1.73-4.30; I2 =40%; 10 studies). There was no statistically significant association between a history of sexual abuse and a lifetime diagnosis of fibromyalgia (OR 1.61; 95% CI, 0.853.07; I2 = 0%; 4 studies), obesity (OR, 1.47; 95% CI, 0.88-2.46; I2 = 71%; 2 studies), or headache (OR, 1.49; 95% CI, 0.96-2.31; I2 =not available; 1 study). We found no longitudinal studies that assessed the outcome of syncope. The results of meta-analyses are depicted in FIGURE 2.
Subgroup Analyses

not found for other outcomes. There were insufficient data to conduct subgroup analyses based on the sex or the race of the abused individual. Subgroup analyses are summarized in TABLE 4. Meta-regression did not reveal a statistically significant association between the quality score and the effect size (P .05 for all outcomes).
Sensitivity Analysis

Publication Bias

Inspection of funnel plots and statistical tests for publication bias did not show an obvious effect of publication bias. However, these analyses were underpowered because of the small number of included studies. COMMENT We performed a comprehensive systematic review of the literature and meta-analysis to assess the association between sexual abuse and the lifetime prevalence of several somatic disorders. This review found that sexual abuse was associated with a lifetime diagnosis of nonspecific chronic pain, functional gastrointestinal disorders, psychogenic seizures, and chronic pelvic pain. There was no statistically significant association between a history of sexual abuse and the lifetime diagnosis of fibromyalgia, obesity, or headache. No data were available to assess the outcome of syncope. When analysis was restricted to studies in which sexual abuse was defined as rape, significant associations were observed between rape and the lifetime diagnosis
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We found no significant subgroup strength of association interactions according to the age of abuse (childhood vs adulthood). Only for the outcome of obesity did we find a significant interaction suggesting higher association in studies with case-control design compared with cohort design. This interaction (design strength of association) was

To determine the effect of sexual abuse category on the estimated association, we conducted a sensitivity analysis, including only those studies that defined sexual abuse as rape (FIGURE 3). A significant association was found between a history of rape and a lifetime diagnosis of fibromyalgia (OR, 3.35; 95% CI, 1.51-7.46; I 2 = not available; 2 studies), functional gastrointestinal disorders (OR, 4.01; 95% CI, 1.88-8.57; I 2 = not available; 1 study), and chronic pelvic pain (OR, 3.27; 95% CI, 1.0210.53; I 2 = not available; 1 study). There were insufficient data to conduct this sensitivity analysis for the other outcomes.

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of fibromyalgia, chronic pelvic pain, and functional gastrointestinal disorders. In studies evaluating obesity, casecontrol studies demonstrated a greater association compared with cohort studies. This observation may be due to type I error or chance. Alternatively, this observation may reflect recall bias in studies of case-control design. To our knowledge, this is the first attempt to summarize the available data on the association between patient history of sexual abuse and somatic out-

comes. Previous systematic reviews empirically evaluating childhood sexual abuse outcomes have revealed increased psychiatric outcomes, behavior problems, victim-perpetrator cycle, and adult maladjustment.10,11,58 Our systematic review builds on this work by expanding it to include somatic sequelae.
Study Strengths and Limitations

Significant strengths of this study include the exhaustive and reproduc-

ible search strategy, attempts to decrease bias by performing selection, review and extraction of data in pairs of reviewers, and communication with authors of original studies to ascertain unpublished or incomplete data. Furthermore, efforts were made to evaluate foreign-language and unpublished studies. Subgroup and sensitivity analyses were conducted to explain heterogeneity. The principal limitation of this study was the use of evidence suscep-

Table 2. Quality Assessment of Reviewed Case-Control Studies a

Exposed and Nonexposed c Controls Cases From Same Population Statement That Controls Have No History of Outcome Matched by Second Factor Adjusted by 1 Factor if No Matching Ascertain Same Same Exposure Method of Response by Blinded Ascertaining Rate for Structured Cases Both Interview Controls Groups

Source Biosset-Pioro et al,19 1995 Ciccone et al,39 2005 Collett et al,40 1998 Delvaux et al,41 1997 Dhanaraj et al,42 2005 Dikel et al,43 2003 Ehlert et al,44 1999 Felitti et al,45 1993 Heim et al,46 1998 Koloski et al,47 2005 Lampe et al,48 2000 Lampe et al,49 2003 Rapkin et al,50 1990 Reinhard,51 2004 Salmon et al,52 2003 Taylor et al,17 1995 Walker et al,5 1993 Walker et al,53 1995 Walker et al,54 1997

Independent Validation

Appropriately Selected b

Matched

a Quality assessment performed with Newcastle-Ottawa scale. A total of 19 studies and 2778 individual data records included. b Must meet all 3 criteria: during defined period; throughout defined area; all cases or appropriate sample of cases (random/consecutive) in a defined group. c No studies met the criteria of adjusting exposed and nonexposed individuals by 1 factor when no matching completed. No studies ascertained exposure via secure records,

including a chart or file.

Table 3. Quality Assessment of Reviewed Cohort Studies a

Exposed Ascertain and Nonexposed b Exposed Exposure Ascertain Follow-up Group Through Random or Demonstration Outcome via Confirm Long Represents Records or Consecutive That Outcome Matched Independent Outcome Enough for Loss to Average in Structured Selection of Not Present at by Second or Blind via Secure Outcome Follow-up Community Interviews Nonexposed Study Start Matched Factor Assessment Record c to Occur 20%

Study Noll et al,55 2007 Raphael et al,56 2001 Rimsza et al,16 1988 Romans et al,57 2002

a Quality assessment performed using Newcastle-Ottawa scale. A total of 4 studies and 1862 individual data records included. b No studies adjusted exposed and nonexposed individuals by 1 factor or 1 factor when there was no matching. c Secure record included a chart or file.

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tible to bias. No studies met all of the Newcastle-Ottawa criteria for quality. Only 2 of 23 studies met at least 8 of the 10 maximum allowed points of the criteria. Analysis with metaregression did not demonstrate an association between study quality (total number of points for each study) and effect size. This lack of association is consistent with previous literature that revealed that summary scores of clinical trials quality do not correlate with treatment effect.59 We did not detect publication bias; however, our analysis was underpowered

because of the small number of included studies.60 Also, unexplained heterogeneity was demonstrated in analyses of the outcomes of functional gastrointestinal orders and obesity. Imprecision caused by the small number of events could have masked a real association between sexual abuse and the outcomes of obesity, headache, and fibromyalgia. In addition, the associations reported in this review could be overstated because of the use of ORs to estimate the risk of a common event. 61 Therefore, the overall level of evidence found by this

review may be reduced by methodological limitations, heterogeneity, and imprecision.62 Also, our results may not generalize to men. Sixteen of the 23 studies in this review were restricted to female subjects, whereas no study evaluated male subjects exclusively. These findings may reflect the higher prevalence rates of sexual abuse against females; however, sexual abuse is known to affect males. Further research investigating males would be worthwhile to determine whether similar sequelae also tend to affect male individuals or whether

Figure 2. Odds Ratio for the Association of Sexual Abuse and Somatic Disorders
Events, No./Total Source Chronic pain Raphael et al,56 2001a Fibromyalgia Boisset-Pioro et al,19 1995 Ciccone et al,39 2005 Taylor et al,17 1995 Walker et al,54 1997 Overall Functional GI disorders Delvaux et al,41 1997 Koloski et al,47 2005 Rimsza et al,16 1988 Romans et al,57 2002 Walker et al,5 1993 Overall Headaches Romans et al,57 2002 Psychogenic seizures Dhanaraj et al,42 2005 Dikel et al,43 2003 Salmon et al,52 2003 Overall Obesity Felitti,45 1993 Noll et al,55 2007 Overall Pelvic pain Collett et al,40 1998 Ehlert et al,44 1999 Heim et al,46 1998 Koloski et al,47 2005 Lampe et al,48 2000 Lampe et al,49 2003 Rapkin et al,50 1990 Reinhard,51 2004 Romans et al,57 2002 Walker et al,53 1995 Overall 12/30 10/12 10/15 11/51 13/20 21/39 6/10 35/52 10/173 29/44 10/60 5/13 3/14 18/100 23/100 59/163 25/53 13/47 7/181 21/56 10.59 4.58 5.52 12.44 9.96 14.21 7.25 12.15 10.68 12.62 25/31 12/84 75/169 10/89 49.46 50.54 67/173 2/3 12/23 25/38 54/181 28/57 5/28 56/124 100.00 12.04 32.88 55.08 62/109 37/55 22/72 13/173 15/16 134/594 119/201 7/68 18/181 13/31 29.25 24.57 18.25 21.96 5.96 Sexual Abuse Control Relative Weight, % 100.00 42/107 23/52 26/48 12/16 41/137 22/53 14/32 24/53 33.46 26.69 23.47 16.38 Odds Ratio (95% CI) 2.20 (1.54-3.15) 1.51 (0.89-2.58) 1.12 (0.52-2.42) 1.52 (0.62-3.74) 3.63 (1.03-12.71) 1.61 (0.85-3.07) 4.53 (2.96-6.93) 1.42 (0.75-2.66) 3.83 (1.51-9.71) 0.74 (0.35-1.55) 20.77 (2.43-177.64) 2.43 (1.36-4.31) 1.49 (0.96-2.31) 2.07 (0.18-24.15) 5.02 (1.41-17.81) 2.34 (1.09-4.98) 2.96 (1.18-7.41) 5.22 (2.04-13.39) 1.32 (0.54-3.23) 1.47 (0.88-2.46) 3.33 (1.23-9.04) 8.00 (1.21-52.99) 7.33 (1.38-38.88) 1.25 (0.54-2.90) 2.91 (1.01-8.37) 2.06 (1.02-4.17) 1.68 (0.42-6.65) 5.38 (2.27-12.76) 1.52 (0.57-4.10) 3.22 (1.41-7.36) 2.73 (1.73-4.30)

0.2

1.0

10

Odds Ratio (95% CI)

CI indicates confidence interval; GI, gastrointestinal. a No event total available.

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this sex is prone to develop different sets of outcomes. Another potential limitation of this study is recall bias. Although 3 of the 4 cohort studies obtained data on sexual abuse exposure from medical or legal documentation, all case-control studies relied on self-reporting from either questionnaires or interviews. However, use of questionnaires or interviews to ascertain exposure may be problematic. Previous studies have found notable variability in the percentage of documented survivors of
Table 4. Subgroup Analysis
Outcome/Subgroup Gastrointestinal disorders Adult abuse Childhood abuse Case-control design Cohort design Fibromyalgia Adult abuse Childhood abuse Headache Adult abuse Childhood abuse Psychogenic seizures Adult abuse Childhood abuse Obesity Case-control design Cohort design Chronic pelvic pain Adult abuse Childhood abuse Case-control design Cohort design

childhood sexual abuse (62%-81%) who recall the abuse as adults.63-65 These statistics indicate that questionnaire respondents or interview subjects likely underreport childhood sexual abuse. The effect of this underreporting would be the inclusion of sexual abuse survivors in control groups. This in turn may diminish the effect size of the association between sexual abuse and somatic outcomes. As an additional point, research shows that emotional, physical, and sexual abuse tend to coexist.29,30 How-

ever, only a minority of studies ascertained whether subjects had been exposed to 1 or multiple categories of abuse. To better define outcomes specifically associated with sexual abuse, we recommend that research studies work to better clarify the type of abuse to which patients have been exposed.
Potential Mechanisms and Implications

To our knowledge, there is no validated theory to explain the association between sexual abuse and chronic

OR (95% CI) 1.23 (0.46-3.26) 1.51 (0.69-3.32) 3.76 (1.15-12.26) 1.63 (0.41-6.48) 7.43 (0.14-389.92) 3.63 (0.07-199.97) 1.35 (0.77-2.40) 1.49 (0.96-2.31) 2.72 (1.23-6.00) 2.87 (1.48-5.59) 5.22 (2.04-13.39) 1.32 (0.54-3.23) 3.03 (1.72-5.33) 2.61 (1.76-3.86) 3.12 (2.13-4.57) 1.52 (0.49-4.71)

No. of Cohorts/ Individuals 2/560 3/750 3/1006 2/494 1/69 1/69 1/354 1/354 1/162 2/213 1/300 1/195 4/668 7/1048 9/838 1/354

I2, % 47 73 83 86 NA NA NA NA NA 3 NA NA 0 35 24 NA

P Value for Interaction a .74 .37

.80

.80

.92

.04

.67 .24

Abbreviations: CI, confidence interval; I2, proportion of heterogeneity not attributable to chance; NA, not available; OR, odds ratio. a Two-tailed P value for the test of interaction (subgroup-associated interaction).

Figure 3. Odds Ratio for the Association of Rape With Somatic Disorders
Events, No./Total Source Fibromyalgia Ciccone et al,39 2005 Walker et al,54 1997 Overall Functional GI disorders Delvaux et al,41 1997 Pelvic pain Collett et al,40 1998 17/29 8/30 179/686 6/60 Rape 15/52 12/16 Control 6/53 24/53 Odds Ratio (95% CI) 3.18 (1.12-8.99) 3.63 (1.03-12.71) 3.35 (1.51-7.46) 4.01 (1.88-8.57) 3.27 (1.02-10.53) 0.2 1.0 10

Odds Ratio (95% CI)

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somatic disorders. Sexual abuse, however, may be an early, inciting environmental factor in a multistep process that culminates in physical dysfunction. Furthermore, neuroendocrine maladaptation may be important to this progression. Animal studies have revealed that early life stress is associated with dysregulation of the hypothalamic pituitary axis.66,67 Hypothalamicpituitary axis dysregulation has also been measured in women with a history of childhood sexual abuse who experience depression and anxiety. Similar findings of hypothalamic-pituitary axis dysregulation were observed in combat veterans with posttraumatic stress disorder.68,69 Evidence also suggests that neuroendocrine changes caused by stress, including dysregulation of corticotropin-releasing factor, may result in neurologic and behavioral changes.70-72 Similar dysregulation of corticotropin-releasing factor has been demonstrated in laboratory animals with colonic dysmotility.72-74 However, the role of hypothalamicpituitary axis dysregulation in chronic pelvic pain and fibromyalgia remains controversial.46,75-77 We speculate that the neuroendocrine system mediates the connection between sexual abuse and the development of somatic dysfunction. Building greater awareness of the association between sexual abuse and somatic disorders may lead to improved health care delivery and outcomes for sexual abuse survivors. As a group, survivors of abuse have higher medical care use and incur greater costs compared with the general patient population.21,78-81 Analysis of expenditures demonstrates that costs are primarily the result of increased use of primary care, specialty medicine, and pharmacy and laboratory services.82,83 Higher medical use may also expose these patients to greater risk without clearly defined benefits, including increased abdominal and pelvic surgeries, adverse effects of medications, and chronic opioid use and dependence.84-89 Despite evidence of high health care use among sexual abuse survivors,

physicians remain largely unaware of this aspect of their patients medical history. Only 5% of sexual abuse survivors report a history of abuse to their physician.5 However, heightened awareness of these specific health associations may prompt earlier recognition and improve care for sexual abuse survivors. One systematic review found that disclosure of childhood sexual abuse memories during psychotherapy may improve posttraumatic stress disorder symptoms, decrease depression, and alleviate anxiety.78 Also, cognitive behavioral therapy and cognitive processing therapy have been found effective in treating posttraumatic stress disorder in survivors of sexual abuse.90,91 We hypothesize that similar therapeutic approaches may be feasible for sexual abuse survivors with somatic sequelae.92 Given evidence of sexual abuse prevalence and related physical and mental health sequelae, we urge physicians to more routinely conduct inquiries about sexual abuse in patients with the identified somatic syndromes. Disclosure of abuse in the clinic setting may allow for earlier consultation with mental health professionals. Prompt recognition of the physical and psychological sequelae of sexual abuse may halt unnecessary medical escalation and provide care better suited to promote recovery. This review highlights the need for future research to better define the nature and scope of mental and physical health outcomes in sexual abuse survivors. As with previous reviews of sexual abuse and psychiatric sequelae, we were unable to more fully ascertain specific mediators of chronic somatic illness, such as duration of abuse, sex of the victim, and socioeconomic factors (eg, family income, single-parent upbringing, parental alcohol use). To more precisely define the temporal relationship between sexual abuse and somatic outcomes, further studies will be necessary. We recommend a prospective cohort study to evaluate somatic outcomes in survivors of abuse, with focused attention on

the potential mediators and modifiers of the associations. This design would also be predicted to better address concerns of potential bias in the literature. Additionally, the premise that disclosure of abuse during psychotherapy improves psychiatric symptoms opens the door to clinical trials to assess the utility of abuse disclosure in the treatment of somatic sequelae. Finally, the success of cognitive behavioral therapy treatment of posttraumatic stress disorder for sexual abuse survivors points to a possible role for this modality for abuse survivors with somatic sequelae. CONCLUSION Sexual abuse remains prevalent and survivors are commonly encountered in general medical practice. Increasingly, it has been shown that survivors of sexual abuse face a spectrum of often challenging health concerns, resulting in greater health care use and cost and significant morbidity. This systematic review and meta-analysis demonstrates an association between sexual abuse and lifetime diagnosis of functional gastrointestinal disorders, chronic nonspecific pain, psychogenic nonepileptic seizure disorder, and chronic pelvic pain. Recognition of this association may have important clinical implications for patients coping with these disorders and their clinicians. Future research should be conducted to better define the epidemiology of this association and improve clinical outcomes for sexual abuse survivors with somatic sequelae.
Author Contributions: Dr Zirakzadeh had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Paras, Murad, Chen, Colbenson, Elamin, Seime, Zirakzadeh. Acquisition of data: Paras, Chen, Goranson, Sattler, Colbenson, Prokop, Zirakzadeh. Analysis and interpretation of data: Paras, Murad, Chen, Elamin, Seime, Zirakzadeh. Drafting of the manuscript: Paras, Murad, Chen, Prokop, Seime, Zirakzadeh. Critical revision of the manuscript for important intellectual content: Paras, Murad, Chen, Goranson, Sattler, Colbenson, Elamin, Seime, Zirakzadeh. Statistical analysis: Murad, Elamin, Zirakzadeh. Administrative, technical, or material support: Paras, Murad, Chen, Elamin, Zirakzadeh. Study supervision: Elamin, Seime, Zirakzadeh. 559

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Financial Disclosures: None reported. Additional Contributions: We thank the Mayo Clinic library staff for their assistance in obtaining the many manuscripts needed to complete this study and also Anne Safley, MD, of University of Iowa Hospitals and Clinics for critical review of the manuscript. We would also like to extend our gratitude to Mary-Ann Fitzcharles, MB, ChB, and Sarah Romans, MD, who returned original data on request. gia syndrome. Arthritis Rheum. 1995;38(2):235241. 20. Drossman DALJ, Nachman G, Li ZM, Gluck H, et al. Sexual and physical abuse in women with functional or organic gastrointestinal disorders. Ann Intern Med. 1990;113(11):828-833. 21. Felitti VJ. Long-term medical consequences of incest, rape, and molestation. South Med J. 1991; 84(3):328-331. 22. Croft P, Boswell R, Schollum J, Silman A. The prevalence of chronic widespread pain in the general population. J Rheumatol. 1993;20(4):710-713. 23. Wolfe F, Anderson J, Russell IJ, Hebert L. 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