Prevalence of endometriosis in women undergoing laparoscopic surgery for various gynecological indications: a Jordanian multi-center retrospective study

Abstract

Background

Endometriosis, a condition that significantly impacts the quality of life for affected women, manifests with a spectrum of symptoms ranging from mild discomfort to severe pelvic pain, dysmenorrhea, dyspareunia, and infertility. A previous single-center study suggested an elevated prevalence of endometriosis in Jordan, prompting the need for larger studies to confirm these findings.

Methods

We conducted a cross-sectional study involving a sample of 866 women who underwent various laparoscopic procedures for different indications at the Department of Obstetrics and Gynecology at Jordan University Hospital and Al-Karak Governmental Hospital, two tertiary referral hospitals in Jordan between January 2015 and March 2023.

Results

Our study included 866 patients who underwent gynecological laparoscopic surgery between 2015 and 2023, with a mean age of 33.80 ± 7.7 years. Of these, 89 women were diagnosed with endometriosis, resulting in an overall prevalence of 10.3%. Diagnostic laparoscopy was the most common procedure, performed on 28.4% of patients. Infertility was the most common indication, observed in 34.5% of patients. Endometriosis was significantly more prevalent in patients with chronic pelvic pain (29.7%) and less prevalent in those seeking treatment for infertility (13.8%), ectopic pregnancy (1.1%), and family planning (0%). Endometriosis was significantly less prevalent in patients undergoing laparoscopic salpingectomy or salpingostomy (3.7%). Backstep-wise multivariate regression analysis suggested that endometriosis may be associated with higher age (OR 1.04, 95%CI 1.00 to 1.07, p = 0.027), lower BMI (OR 0.92, 95%CI 0.87 to 0.98, p = 0.007), lower number of parities (OR 0.72, 95%CI 0.6 to 0.86, p < 0.001), and fewer cesarean sections (OR 0.53, 95%CI 0.32 to 0.87, p = 0.013).

Conclusion

This is the most extensive Jordanian study assessing the prevalence of endometriosis in women undergoing gynecological laparoscopy. Our results suggest that the prevalence of endometriosis among Jordanian women remains high, albeit lower than previously reported. The study uncovered that age, BMI, parity number, and cesarean sections are predictors of endometriosis. Future research may explore causative reasons for the higher prevalence of endometriosis and the influence of other comorbidities, medications, and lifestyle factors.

Introduction

Endometriosis is a chronic inflammatory condition characterized by the deposition of endometrial-like tissue in ectopic places outside the uterine cavity, such as ovaries, fallopian tubes, and the tissue lining the pelvis [1, 2]. Endometriosis affects women of reproductive age, and it manifests with a spectrum of symptoms, ranging from mild discomfort to severe pelvic pain, dysmenorrhea, dyspareunia, and infertility. This condition significantly lowers the quality of life for affected women [1].

Around 1 in 10 women worldwide are affected by endometriosis. This condition affects females of reproductive age [2, 3]. However, the prevalence of diagnosed endometriosis in women in the United States is lower at around 6.1% [4]. A systematic review of 47 studies on common gynecological diseases conducted in the Middle East found that 12.9% of women who underwent laparoscopy for any reason were diagnosed with endometriosis [5]. In the Hashemite Kingdom of Jordan, a study conducted on 460 patients who underwent laparoscopy at a university hospital revealed a prevalence of endometriosis of 13.7% [3].

More than 30,000 papers in the literature discuss adenomyosis and endometriosis. Several factors have been identified to be associated with a greater risk of developing endometriosis, such as early menarche (onset of menstruation), shortened menstrual cycle length, increased menstrual flow, lean body size (low body mass index (BMI)), and first-degree family history. In contrast, multiparity has been associated with lower risk for endometriosis. However, despite the abundance of information available and ongoing research, the precise etiology of endometriosis remains ambiguous [1, 6]

The gold standard for diagnosing endometriosis involves laparoscopic visualization of lesions followed by histopathological confirmation. However, recent guidelines have shifted towards a non-surgical approach, focusing on patient symptoms, physical exam findings, and imaging for diagnosis [1, 2]. Nevertheless, endometriosis remains significantly underdiagnosed due to a confluence of factors. These include the variable nature of symptoms, limited awareness and knowledge among both healthcare providers and patients, the societal tendency to normalize women's pain, and the overlapping symptoms with other conditions like adenomyosis, irritable bowel syndrome, and interstitial cystitis [1, 3].

This study builds upon previous research investigating the prevalence of endometriosis in Jordanian women undergoing laparoscopy. By incorporating a larger sample size and including data from multiple healthcare centers across the Hashemite Kingdom of Jordan, this research aims to determine the overall prevalence of endometriosis in Jordan. It seeks to examine the prevalence of endometriosis according to the indication for laparoscopy and the type of laparoscopic procedure. Furthermore, the study aims to analyze the prevalence of endometriosis in relation to demographic characteristics, parity, number of miscarriages, ectopic pregnancies, and cesarean sections. Additionally, this research endeavors to identify the univariate and multivariate predictors of endometriosis.

Methods

Study type

Our study was a cross-sectional analysis study conducted at two tertiary referral hospitals in Jordan—the Department of Obstetrics and Gynecology at Jordan University Hospital and Al-Karak Governmental Hospital.

Inclusion and exclusion criteria

Our study included female patients of reproductive age (16–50 years) who underwent gynecological laparoscopy from January 2015 to March 2023. We excluded patients who were outside the age range of 16–50 years or those who had a prior diagnosis or treatment for endometriosis before the index surgery. Additionally, no exclusion criteria were set based on comorbidities such as diabetes or hypertension.

Data collection

Eligible patients for this study were identified from clinical and theatre records, all of whom underwent gynecological laparoscopy. The data collection process was conducted retrospectively through a comprehensive review of the patient’s electronic medical records. Researchers had to visit the hospital multiple times for data extraction, as the data was available from the hospital patient management system accessed only on-site. The data collection process lasted three months, from March 2023 to June 2023.

The diagnosis of endometriosis was established by a team of experienced consultants at Jordan University Hospital and Al-Karak Governmental Hospital, all of whom possess extensive experience in laparoscopic surgery and the diagnosis of endometriosis. Cases were confirmed based on the documented presence of endometriotic lesions (subtle, typical, cystic, or profound) within the electronic operative notes associated with laparoscopic surgery. When histological examination of tissue samples was available, these were cross-referenced with clinical findings, resulting in a 100% concordance rate between clinical and histological diagnoses.

Ethical approval

The study was conducted according to the guidelines of the Declaration of Helsinki. The ethical approval was granted by the Ethics Committee, Faculty of Medicine, Mutah University (protocol reference no. 972023, issued on January 30, 2023). As patient information was handled anonymously, the need for informed consent was waived by the reviewing Ethics Committee at Mutah University.

Statistical analysis

We used PQStat v.1.8.6.122 and IBM SPSS Statistics 27 to perform the statistical analysis. Continuous data was reported as mean ± standard deviation (SD) and median and interquartile range (IQR). Differences between non-normally distributed continuous variables (age, BMI, weight, and height) were measured using the Mann–Whitney U Test (after assessing the normality using the Shapiro–Wilk test). The prevalence of endometriosis was reported as n (%), and the p-value of the chi-square test tested the difference between observed and expected frequencies for overall indications or procedures. An adjusted residual greater than 2 or less than −2 is considered significant to determine the particular significant indication or procedure. Univariate logistic regression and backstep-wise multi-regression analysis were carried out to predict the occurrence of endometriosis, and results were reported as odds ratio (OR) and 95% confidence intervals (95% CI). A p-value of less than 0.05 was considered statistically significant for all tests. Finally, the sample size was calculated prior to the data collection phase using the formula below

$$n=\frac{{Z}^{2}\times P\times (1-P)}{{d}^{2}}$$

Using a (Z) value of 1.96 for a 95% confidence interval, a margin of error (d) of 0.05, and a prevalence (P) of endometriosis of 0.137 from the literature.

Results

Study sample demographics:

Eight hundred sixty-six patients who underwent gynecological laparoscopic surgery between 2015 and 2023 were included in this study, with a mean age of 33.8 ± 7.7 years. 184 patients were confirmed using histological data. Characteristics of the included sample, including age, BMI, height, weight, parity, and number of miscarriages, ectopic pregnancies, and cesarean sections, are illustrated in Table 1.

Table 1 Main demographic characteristics of patients included in the study sample

Overall prevalence of endometriosis

There were 89 women with endometriosis and 777 without endometriosis, making the overall prevalence of endometriosis 10.3%. Diagnostic laparoscopy was the most common procedure for 246 (28.4%) patients. Infertility was the most common indication in 299 (34.5%) patients. Figure 1 contains the types of laparoscopic surgeries performed on this study's patient sample and their indications.

Fig. 1

Frequencies of (a) types of laparoscopic surgeries and (b) indications for laparoscopic surgeries performed on 866 patients

Prevalence of endometriosis according to the indication for laparoscopy

There was a significant difference in the indication frequency for laparoscopy with endometriosis (p < 0.001). Endometriosis was found to be the most common in chronic pelvic pain (29.7%), infertility (13.8%), and ovarian cysts (11.9%). No endometriosis cases were reported in cases of family planning or pelvic inflammatory disease. Residual analysis revealed a significant difference in the frequency of infertility, ectopic pregnancy, chronic pelvic pain, and family planning (Table 2).

Table 2 Numbers and percentages of patients with versus without evidence of endometriosis according to the indication for laparoscopy

Prevalence of endometriosis according to type of laparoscopic procedure

There was a significant difference in the frequency of different procedures with endometriosis (p = 0.023). Endometriosis was found to be the most common in failed laparoscopy (50%); however, there were only two patients in this category, making this procedure negligible. Comparable results were for diagnostic laparoscopy whether with dye test or not, with approximately (13.5% each). Endometriosis was less prevalent in laparoscopic salpingectomy or salpingostomy and tubal ligation, bilateral or unilateral, and residual analysis showed a significant correlation with the former procedures at 3.7% compared with 96.4% in no endometriosis group (Table 3).

Table 3 Numbers and percentages of patients with versus without evidence of endometriosis according to the type of laparoscopic procedure

Prevalence of endometriosis according to demographic characteristics, parity, number of miscarriages, ectopic pregnancies, and cesarean sections.

Compared with patients without endometriosis, women with endometriosis had significantly less weight [67 (60, 76.8) vs. 70 (64, 80), p = 0.009] and less body mass index [25.5 (23.4, 29.1) vs. 27.2 (24.8, 30.1), p = 0.001). No significant relationship was found between age and height (Fig. 2).

Fig. 2

Differences between patients with and without evidence of endometriosis according to (a) age, (b) weight, (c) body mass index, and (d) height. Red stars denote statistical significance between the two groups

We found a statistically significant relationship between endometriosis prevalence and parity number (p < 0.001), ectopic pregnancies (p = 0.016), and cesarean sections (p < 0.004). Most importantly, the significance remained even after applying the Bonferroni correction among the groups. In contrast, for the association between endometriosis and the number of miscarriages, despite its initial significance (p = 0.025), no significant differences were found after the Bonferroni correction. However, we observed a trend (p = 0.003). The trend analysis indicates a clear pattern, where the prevalence of endometriosis decreases as the number of miscarriages increases (Table 4).

Table 4 Numbers and percentages of patients with versus without evidence of endometriosis according to parity and number of miscarriages, ectopic pregnancies, and cesarean sections

Regarding the number of parities, endometriosis was most prevalent among individuals with zero parity, with a percentage of 15.6%, and was less common among those with two or three or more parities. Also, endometriosis was most prevalent in those having 0 ectopic pregnancies (10.9%) and none of those with one ectopic pregnancy – we observed that three patients overall had two ectopic pregnancies, making this variable negligible. Finally, concerning cesarean sections, patients with endometriosis were more prevalent in having no cesarean Sects. (12.8%) (Table 4).

The letters "a" and "b" denote significant relationships observed in multiple comparisons using Bonferroni corrections. Digits with the same letter differ significantly.

Predictors of endometriosis

Backward stepwise multi-regression analysis

Parity, age, body mass index, and cesarian section were all retrained in backward stepwise multi-regression analysis. This suggests that endometriosis may exist in women with higher age (OR 1.04, 95%CI 1.00 to 1.07, p = 0.027), lower BMI (OR 0.92, 95%CI 0.87 to 0.98, p = 0.007), lower number of parties (OR 0.72, 95%CI 0.6 to 0.86, p < 0.001), and lower cesarian sections (OR 0.53, 95%CI 0.32 to 0.87, p = 0.013) (Table 5).

Table 5 Backward stepwise multi-regression analysis of endometriosis

Discussion

Our study found that the prevalence of endometriosis was 10.3%. The most common procedure performed on patients was diagnostic laparoscopy. The primary indication for these procedures was infertility. We observed that endometriosis was significantly more prevalent in patients with chronic pelvic pain and less commonplace in those seeking infertility treatment and family planning. Furthermore, endometriosis was less prevalent in patients undergoing laparoscopic salpingectomy or salpingostomy. Despite its prevalence as exemplified in this study, it is important to note that diagnostic laparoscopy has severe limitations. For instance, diagnostic laparoscopy with white light imaging often fails to adequately differentiate between subtle tissue changes and small lesions, which can result in missed diagnoses, particularly in early-stage or mild endometriosis [7, 8]. Moreover, the positive predictive value of white light laparoscopy for diagnosing endometriosis has been reported to be only 66%, highlighting the risk of diagnostic errors due to the polymorphic nature of endometriotic lesions [9].

When comparing patients without endometriosis to those with the condition, we found that women with endometriosis had significantly lower weight and body mass index. However, no significant relationship was found between endometriosis and age or height. Our analysis revealed a statistically significant relationship between the prevalence of endometriosis and the number of parities, ectopic pregnancies, and cesarean sections. No such relationship was observed between endometriosis and the number of miscarriages.

In terms of predictors of endometriosis, univariate analysis showed that lower parity and cesarean sections were associated with the condition. Multivariate analysis revealed that lower parity, higher age, lower body mass index, and fewer cesarean sections were significant predictors for endometriosis.

Compared with the previous single-center study in the same region by Muhaidat et al. [3], evidence of endometriosis was found in 10.3% of women compared with 13%. Still, it almost fits the global prevalence of endometriosis, which affects about 6 to 10% of women worldwide [10]. Concerning the demographic characteristics, we observed that the mean BMI was significantly higher in the group without endometriosis than the group with endometriosis, unlike the previous study in the same region, which showed no significant differences between the two groups [3]. Our results are similar to those reported by Ferrero et al. as they indicated that women with endometriosis have lower BMI and are less frequently obese than control [11]. However, other studies in different areas with more participants showed different results. Tang et al. study involved 1516 women in China and reported that overall, there was no association between BMI and the incidence of endometriosis. However, there was a significant increase in the incidence of endometriosis in obese women compared with women with average weight [12]. In Canada, Hemmings et al. included 2777 women and showed no significant association between BMI and endometriosis [13]. In Greece, Matalliotakis et al. found that BMI trended lower in women with endometriosis than in the control group but did not quite reach statistical significance [14]. The mechanisms underlying this association may involve hormonal pathways, particularly the role of estrogen. Adipose tissue is a significant source of estrogen production, and higher levels of body fat can lead to increased estrogen levels, promoting the growth of endometrial tissue [15]. Conversely, women with lower BMI may have reduced estrogen levels, potentially creating a different hormonal milieu that could influence the development of endometriosis [15]. Additionally, the dysregulation of metabolic pathways in women with endometriosis has been observed, suggesting that endometriosis may alter body weight regulation and metabolic function [16]. Despite these well-established pathway(s), it is crucial to emphasize that the research on the association between BMI and the menstrual cycle is complex; for example, Silvestris et al. mentioned that the majority of obese women have regular ovulatory menstrual cycles remain fertile [17]. Furthermore, women with obesity were twice as likely as normal-weight women to have an irregular menstrual cycle [18]. Hence, the anovulatory cycles and BMI association may explain the apparent difference in the risk of endometriosis between the two groups.

The mean age is slightly lower in the group with endometriosis than in the group without endometriosis. However, this difference is not statistically significant. Endometriosis can affect women of all ages, but it is most commonly diagnosed in women in their 30s and 40s [2]. These results are comparable with the previous study, as they reported an approximately similar age group [3]. Notably, earlier studies in Jordan reported younger age; for example, Al-Jefout et al. had an average age of participants of 18.4, and they included only 28 females – their inclusion criteria were females aged ≤ 21; hence, the results should be interpreted with caution. In a large study involving 62,323 women, Abbas et al. reported that The highest prevalence was observed in women aged 35–44, with 12.8 per 1000 women [19]. Generally, data on the association of age with endometriosis are conflicting in various studies [13, 20]. However, an observation was noted by Hemmings et al., who said that when considering all patients from the study as a single group, a notable correlation was observed between age and endometriosis. This correlation, however, appears to stem from the uneven distribution of cases and controls across the three surgical subgroups. This correlation disappeared when the analysis was carried out within each surgical category. The discrepancies in surgical indications and procedures, frequently overlooked in epidemiological research on endometriosis, could be the source of the inconsistent data concerning the relationship between age and endometriosis [13].

Previous research reported the frequencies of indications of laparoscopy, laparoscopic procedure, parity and number of miscarriages, ectopic pregnancies, and cesarean sections [3]. The authors noted that the highest prevalence of indication of laparoscopy was 31.3% for chronic pelvic pain, followed by infertility (16.9%). In our study, we reported similar results, with a prevalence of 29.7% and 13.8%, respectively, for chronic pelvic pain and infertility. Other research also highlighted the top reasons for women having laparoscopy: infertility, undergoing laparoscopic sterilization, or chronic abdominal and pelvic pain [21]. Our study did not mention laparoscopic sterilization, which might be related to cultural reasons. The mechanisms underlying the association between endometriosis and chronic pelvic pain are multifaceted and involve several biological pathways. One proposed pathway is the inflammatory response elicited by ectopic endometrial tissue. The presence of this tissue leads to local inflammation, which can sensitize nociceptive pathways and contribute to the perception of pain [22, 23]. Additionally, the ectopic endometrial tissue produces inflammatory mediators such as prostaglandins, which are known to exacerbate pain [22]. Prostaglandin E2 has been identified as a key player in the pathophysiology of endometriosis-related pain, as it can enhance pain sensitivity and promote the development of chronic pain syndromes [22].

Concerning the procedure, previous research did not report a significant association between women with and without evidence of endometriosis according to the type of laparoscopic procedure [3]. Increasing the sample size in our study showed that Laparoscopic salpingectomy or salpingostomy was more prevalent in patients without endometriosis. McGuinness et al. suggested that there may be a role for salpingectomy at the time of laparoscopic treatment of endometriosis in patients with severe pain symptoms and on completion of childbearing. In this study, it might be related to childbearing; however, further observational studies are needed to evaluate this [24]

Results of parity, miscarriages, and cesarean sections were similar to those reported earlier, and ectopic pregnancies in our study reached power for statistical significance. Most importantly, lower Parity numbers and lower cesarean sections were univariate and multivariate predictors for endometriosis. Horne et al. [2] suggested that endometriosis may impair fertility through multiple pathways, including peritoneal inflammation and endocrine derangements, which interfere with the follicular environment, consequently affecting ovarian function and ultimately reducing oocyte competence. Bonavina and Taylor highlighted that the population of infertile women with endometriosis is heterogeneous, and diverse patients' phenotypes can be observed in the clinical setting, thus making it difficult to establish a precise diagnosis and a single mechanism of endometriosis-related infertility [25]. Despite the clinically recognized association between endometriosis and infertility, the condition is currently considered multifactorial. Therefore, we suggest that future prevalence studies consider multifactorial analysis rather than only reporting the frequencies to provide more insightful information on the disease in the particular region.

Strength and limitations

We conducted a multi-center study in Jordan, encompassing a sample size almost twice as large as those reported in previous studies. This larger sample size enhanced our statistical power, allowing us to uncover more insights into factors such as the role of BMI and weight in this population. However, some limitations should be acknowledged. Firstly, we did not account for any comorbidities in our study. This omission could make it challenging to establish causative relationships from the associations and prevalence rates observed in our study. Second, results were not normally distributed; we minimized this by conducting non-parametric tests and confirmed the results by regression analysis. Third, retrospective studies are prone to selection bias, and the subjects were not randomly selected. Finally, it is important to note that while this study measured for endometriosis, it did not differentiate between superficial and deep infiltrating forms of the disease. Superficial endometriosis, which accounts for approximately 80% of cases, and deep infiltrating endometriosis, which can lead to more severe symptoms and anatomical distortions, may require distinct diagnostic approaches [26, 27]. The lack of stratification by endometriosis subtype could limit the granularity of our findings, particularly in terms of symptom severity and treatment outcomes.

Conclusion

The prevalence of endometriosis in Jordanian women (10.3%) is higher than the global prevalence but lower than the prevalence reported in the Middle East region. Lower parity, higher age, lower BMI, and fewer cesarean sections are the predictors of endometriosis for the study population. Future studies may investigate the reasons for higher salpingectomy procedures in women without endometriosis and also the confounding diagnostic, genetic, and lifestyle factors that exist along with age and BMI for this particular population.