Life-time experience of violence as a risk factor for symptomatic endometriosis

Abstract The aim of this questionnaire study is to investigate the impact of life-time experiences of violence on the course and severity of endometriosis at a University Endometriosis Center. It also explores women’s attitudes toward medical screening for violence. The questionnaire covered demographic data, medical data, information involving possible experiences of psychological, physical, sexual, and intimate partner violence as well as violence screening in medical care. Questionnaires of 118 participants were analyzed. 41/118 women reported some form of violence (34.8%). These women had a significantly higher risk for severe dysmenorrhea, use of analgesics, and comorbidities in comparison to women without life-time experiences of violence. Statistically significant differences were also found for employment status and impaired working ability. More than 60% of women considered the aspect of violence as important for health. However, only 17.1% of women with experiences of violence recalled being asked about violence by a medical professional. The study results suggest that experiences of violence have a significant impact on the course and severity of endometriosis. The findings highlight the importance of healthcare providers to be aware of the potential impact of violence on women’s health, and routine screening for violence in medical care, especially in women with endometriosis.


Introduction
Endometriosis is a common disease that affects various aspects of life.It is estimated that one out of ten women of reproductive age has endometriosis [1].In addition to a direct negative impact of the quality of life through pain at the days of menstruation [2], endometriosis may also impair sexuality, relationship, fertility, and working situation [3,4].The psychosocial effects of endometriosis are comparable to diabetes mellitus or rheumatoid arthritis [5].
Life-time experiences of violence are a burden for health.According to the World Health Organization 30% of women worldwide have experienced either physical and/or sexual violence [6].Similar percentages can be assumed for Germany [7].Violence not only has direct physical consequences but also long-term effects on psychosocial and medical well-being, increasing the risk of chronic diseases [8].Women who experienced intimate partner violence showed a significantly higher prevalence of chronic diseases in comparison to women without this risk factor [9], especially if physical or sexual violence occurred in childhood or adolescence [10].
Recent research suggests an association between dysmenorrhea, pelvic pain and adverse childhood experiences [11,12].A large prospective cohort study has also found a significantly higher risk of endometriosis in women with a history of severe physical or sexual violence compared to those without violence [13].The authors suggested that healthcare providers should routinely screen women with endometriosis for violence in childhood to avoid long-term sequelae.Routine screening for violence in medical care is mainly based on two purposes: � To identify actual threatening life-situations, in order to optimally manage imminent health problems as well as preventing re-exposure � To detect women with life-time experiences of violence as a risk factor for different health outcomes and, therefore, optimizing patient-centered care Different tools to assess violence are already used in the settings of emergency departments or obstetric wards.Face to face interviews with simple questions or complex questionnaires are suggested [14].Up to now, sufficient evidence on the optimal screening, adverse screening effects or optimized care after positive screening, is still lacking.
This questionnaire study aims to evaluate the potential impact of life-time experiences of violence on symptoms of endometriosis in women with histologically confirmed endometriosis, comparing them with women without experience of violence.Additionally, the study explores women's perceptions and attitudes on screening for violence in women with endometriosis.

Materials and methods
1,332 women with histologically confirmed endometriosis were treated in a university-affiliated endometriosis-center between 2013 and 2018.1,297 women were contacted via postal mail in 2019 to participate in this monocentric questionnaire study.482 (37.2%) women returned the invitation letter.N ¼ 314 gave informed consent for further study information and N ¼ 126 (40.1%) completed the online questionnaire (Supplementary Material).The questionnaire was divided into three parts covering demographic data, data about the course of disease and life-time experiences of violence (Supplementary Material).Questions about experiences of violence included psychological, physical, sexual and/or intimate partner violence.All participants were asked to share their attitudes about integrating questions about experiences of violence into the medical history of patients with endometriosis as standardized routine.Participants were asked to give informed consent and confirm the privacy protection policy electronically.The study protocol of the questionnaire study was approved by the ethic committee of the Institutional Review board (EK 64022019).
LimeSurvey software was used for the online survey and IBM SPSS Version 25 (SPSS Inc., Chicago, IL, USA) for statistical analysis.Continuous variables are presented as mean, standard deviation and range.Normal distribution was tested using the Kolmogorov-Smirnov test.Two-sided t-test for independent samples was used for normally distributed variables and Mann-Whitney-U-test for not normally distributed variables.For categorical variables, Pearson's chi-square test was used, Exact-Fischer-Test was used for small sample sizes.The significance level was set at p < 0.05.

Results
Clinical data are available for the initial group of 314 patients with endometriosis who agreed to participate in the study.These patients had an age of 34.5 ± 7.0 (18-45) years and most commonly reported pelvic pain or dysmenorrhea (N ¼ 165, 52.6%) and infertility (N ¼ 112, 35.7%).Almost all of these patients had undergone at least one surgery related to endometriosis (310/314, 98.7%), in average 1.3 ± 0.8 (0-8) procedures.The diagnosis of endometriosis in the remaining cases without surgical procedures was confirmed through biopsies of vaginal or cervical tissue.The latency between symptom onset and diagnosis was 10.6 ± 8.0 years.The intraoperative findings were classified according to rASRM (revised American Society of Reproductive Medicine) and ENZAIN classification from 2012 [15].Stage rASRM I was reported in 34.8% of patients, rASRM II in 29.2%, higher-grade stages III and IV occurred in comparable frequency with 19.3% and 16.7%.In women with deep infiltrating endometriosis (DIE) (N ¼ 161, 52.3%) multiple affected compartments were found in 35 (21.7%) women.Involvement of the B compartment was documented in 55.3% (89/161) as the most common localization of DIE.
The 126 active participants of the questionnaire study were slightly older and had a mean age of 38.0 years.Almost all participants were of German origin, heterosexually oriented and mostly in a steady relationship (Table 1).Information about life-time experiences of violence was provided by 118 women.Of them, N ¼ 41 (34.8%) reported life-time experiences of violence.Among them, 52.5% stated that they were younger than 14 years at the time of victimization.8/41 women (19.5%) reported one event, 13/41 women (31.7%) 2-5 events, 6/41 women (14.6%) 6-10 events, and 14/41 women (34.1%) more than ten events.The types of violence are shown in Figure 1.
Table 1 shows the sociodemographic characteristics of the participants in groups with and without experiences of violence.Statistically significant differences are shown for employment status (p ¼ 0.001) and impairment of working ability due to endometriosis (p ¼ 0.008).
Group comparisons regarding health-related parameters are presented in Table 2.No significant differences were found regarding surgical therapy, frequency of surgical procedures and improvement of endometriosis related pain after surgery.Nevertheless, significantly higher rates of endometriosis related pain, analgetic use as well as higher severity of pain were seen in women who experienced violence in comparison to women without a history of violence.Other chronic diseases were also significantly more frequent in women with experiences of violence.
Table 3 shows the comparison between the women with/without experiences of violence considering individual perceptions and attitudes about the screening for violence.The majority of 60% of women considered screening for violence important without differences in the two groups.Only the question if the topic of violence ever occurred during gynecological consultations, revealed differences.Women with a reported history of violence recalled being asked about violence by a medical professional in 17.1% whereas in the group without experienced violence only one woman was asked (p < 0.001).Most of the patients in both groups had a positive attitude toward addressing the aspect of violence during a medical treatment in general and especially for patients suffering from endometriosis.

Discussion
About 30% of women experience violence during their lifetime.A WHO study published in 2018 included data from 2 million women of 161 countries [16]: 27% of women had experienced intimate partner violence, 13% in the last years.Our study showed that in a group of 118 women with endometriosis answering an online questionnaire with 34.8% a similar percentage of women reported violence in their life-time in Germany as reported worldwide.
Experiences of violence in childhood or adolescence increase the risk for endometriosis [11,12].But it can also be assumed that life-time experiences of violence can negatively affect the course of endometriosis.Currently endometriosis is defined as a chronic and systemic disease with impact on the immune system and pain sensitization [17].The association between  experiences of violence and increased pain sensitization has been previously reported, especially in women who have experienced maltreatment and abuse in childhood [18].In our study women with life-time experiences of violence have a significantly higher percentage of dysmenorrhea despite effective treatment options.The intensity of pain was also rated significantly higher.These findings suggests that experiences of violence have a long-lasting impact on pain sensitization and may contribute to the chronic pain associated with endometriosis.Mechanisms by which experiences of violence affect pain sensitization in women with endometriosis, such as neurobiological and psychological pathways should be explored in detail.We also found an increased risk for concomitant chronic diseases, impaired working ability and unemployment in women with endometriosis and experiences of violence.Endometriosis itself has a significant negative impact on the socioeconomic status [5].Other studies show a higher risk for mental diseases in women with endometriosis and increased pain [2].Our study's results add evidence for the interaction between endometriosis and life-time experiences of violence which may also have significant consequences on a woman's socioeconomic status.
These findings underscore the need for better screening and support for women with endometriosis who have experienced violence.The questions if or how to screen for violence in routine care are still not answered.In a Cochrane meta-analysis, 13 trials with 14,959 women were included in controlled studies with screening for intimate partner violence [19].But heterogenic settings and study protocols as well as low quality of the studies impaired the results of the meta-analysis.In antenatal care, maternal health services and emergency departments the screening seems  Categorical data with n (%) and metrical data (mean ± SD), (n); � significant statistical difference at <5% level.
to be effective with high identification rates.Screening for violence should be done in a safe and supportive environment.All professionals in medicine should be aware of local resources available for women experiencing ongoing threatening life-situations.A special training for healthcare professionals to communicate and offer appropriate resources and possible referrals is needed.
Coping programs for women with endometriosis should integrate screening for violence and consider this aspect for individually tailored coping programs.After identifying women with the risk factor due to experienced violence, psychosocial interventions should be recommended.According to a Cochrane meta-analysis of 33 randomized controlled studies, psychological interventions for women who experience intimate partner violence are effective in reducing the risk of depression and anxiety [20].Multidisciplinary approaches are useful to address the complex biopsychosocial impact on the quality of life in women with endometriosis and life-time experiences of violence.
Sims et al. [21] recommended to increase the efforts to study endometriosis-related risk factors and developing interventions that modify the multidimensional negative effects of endometriosis on quality of life.Experience of violence can have a significant impact on the course and outcome of endometriosis, as well as on women 0 s life quality.

Strengths and limitations
This study was conducted at a certified endometriosis center in a university hospital, which may result in an overrepresentation of moderate-to-severe endometriosis, severe pain, and more comorbidities.The study had a high proportion of women with deep-infiltrating endometriosis, reflecting the nature of the center as a referral facility for complex cases [22].This study was conducted at a certified endometriosis center in a university hospital, which may result in an overrepresentation of moderate-to-severe endometriosis, severe pain, and more comorbidities.The study had a high proportion of women with deep-infiltrating endometriosis, reflecting the nature of the center as a referral facility for complex cases [22].
The study also encounters important limitations that should be acknowledged.The lack of validation and standardization of the questionnaire limits the generalizability of the findings.The questionnaire was tailored to the study's requirements, using concise questions with an average response time of 7.6 ± 5.4 min.However, standardized and validated questionnaires are more comprehensive.
The complexity of the inclusion procedure, which involved postal invitations, written consent, and e-mail contact to provide the digital link to the online questionnaire contributed to a low participation rate.About 40% of women who expressed interest in participating answered the questionnaire.This self-selection bias and potential recall bias may affect the validity of our findings.Moreover, the sample of women included into the study may not be fully representative of all women with endometriosis, particularly those with lower stages of the disease and ethnic minority backgrounds.The lack of diversity also limits the generalizability of the results.The small sample size for certain subgroups restricted the analysis of differences in childhood experiences, types of violence, and frequency.

Conclusions
This study shows that experience of violence is a significant risk factor for pain sensitization or ineffective treatment in women with endometriosis with impact on the general health and socioeconomic situation.Routine screening for experiences of violence and appropriate interventions could lead to improve pain management and quality of life of these women.
Efforts should be made to increase awareness among healthcare providers about the potential impact of life-time experiences of violence on the course and severity of endometriosis.This includes education on how to identify and screen for experiences of violence and how to provide appropriate referrals for further support and care.A more comprehensive care and support should be based on a multidisciplinary approach addressing medical, psychological, and social aspects of care.
We propose to screen women with endometriosis routinely for experiences of violence.Screening is useful if it detects women at risk and if screening methods are available, easy to use and not harmful.Further research should involve larger and more diverse populations along with inclusive groups of women at all stages of endometriosis and the utilization of standardized and validated questionnaire as EHP-30 [23] or EHP-5 for endometriosis and DVQ-VP [24] or CADRI [25] for violence.
A prospective study design also allows a better understanding of the temporal relation between experiences of violence and course of endometriosis.In a larger study population, possible differences of the type of violence experienced by women with endometriosis and how these may vary across different stages of the disease can be explored.

Figure 1 .
Figure 1.Different types of violence in women reporting experiences of violence (N ¼ 41/118).

Table 1 .
Sociodemographic characteristics of women with and without a history of violence (N ¼ 118).

Table 2 .
Health-related characteristics in study groups.

Table 3 .
Patient's perceptions and attitudes regarding the screening about previous violence (N ¼ 118).