Effect of Endometriosis on Surgical Outcomes of Total Laparoscopic Hysterectomy for Benign Indications: A Propensity Score-Matched Analysis

Introduction The objective of the study was to retrospectively evaluate the impact of endometriosis on perioperative outcomes in patients undergoing total laparoscopic hysterectomy (TLH) for benign diseases.

Among 836 patients who underwent TLH for benign conditions at our institution between January 2011 and December 2024, patients were divided into two groups: those with endometriosis (n = 115) and those without endometriosis (n = 721). Propensity score matching (PSM) was performed to balance baseline characteristics. After matching, 115 patients were included in each group. Perioperative outcomes were compared, including the incidence of surgical site infection (SSI), bowel injury, urinary tract injury, and deep venous thrombosis (DVT).

Before PSM, the endometriosis group had significantly higher rates of superficial and deep incisional SSI (4.3% vs. 1.2%, p = 0.032) and organ/space SSI (15.7% vs. 3.9%, p < 0.001) compared with the non‐endometriosis group. The incidence of intraoperative bowel injury was also significantly higher in the endometriosis group (3.5% vs. 0.3%, p = 0.004). In contrast, there were no significant differences between the groups in urinary tract injury (2.6% vs. 1.2%, p = 0.221) or DVT (0.9% vs. 0.1%, p = 0.256). After PSM, the incidence of organ/space SSI remained significantly higher in the endometriosis group (p = 0.032), whereas no significant differences were observed in superficial plus deep incisional SSI, bowel injury, urinary tract injury, or DVT.

Endometriosis was associated with an increased incidence of organ/space SSI in patients undergoing TLH for benign diseases.

bowel injury, complications, endometriosis, surgical site infection, total laparoscopic hysterectomy, urologic complications 1. Introduction The presence of endometriosis at the time of hysterectomy is associated with increased perioperative morbidity [1], primarily due to distortion of normal pelvic anatomy and the presence of dense adhesions. These changes may increase surgical complexity and adversely affect perioperative outcomes such as operative time, blood loss, conversion to laparotomy, and overall complication rates [2, 3]. In addition, advanced endometriosis may further increase the risk of injury to adjacent organs, including the ureter, rectum, and hypogastric nerves. To date, no randomized controlled trials comparing surgical outcomes of total laparoscopic hysterectomy (TLH) between patients with and without endometriosis have been reported. Accordingly, most available evidence is derived from retrospective studies, and the results remain inconsistent, possibly due to differences in study design, patient selection, and analytical approaches. Endometriosis has also been proposed to reflect a chronic inflammatory condition of the pelvis, which may predispose patients to infectious morbidity, such as pelvic inflammatory disease (PID) and tubo‐ovarian abscess (TOA) formation [4, 5, 6]; however, evidence supporting this association remains conflicting. Whether this potential biological association translates into differences in perioperative outcomes after hysterectomy remains uncertain. Overall, the independent impact of endometriosis on perioperative outcomes following TLH remains incompletely understood. The objective of the current study was to evaluate the impact of endometriosis on perioperative outcomes in patients undergoing TLH for benign diseases using propensity score‐matched analysis. 2. Materials and Methods The Institutional Review Board (IRB) of Osaka Rosai Hospital approved the present study (IRB approval number: 2025‐1; date of approval: April 25, 2025) and granted an opt‐out recruitment approach and waived the requirement for written informed consent from each patient. The document of ethical approval for the present study is available on the website of Osaka Rosai Hospital. 2.1. Data Source and Clinical Information Medical records at Osaka Rosai Hospital from January 2011 to December 2024 were retrospectively reviewed, and 836 patients who underwent TLH for benign indications were identified and analyzed in this study. Of the 836 patients, 721 patients did not have endometriosis, and the remaining 115 patients had endometriosis (Figure 1). Endometriosis was diagnosed based on a combination of intraoperative findings and histopathological examination. The following baseline data were collected: age, parity, body mass index (BMI), the presence of diabetes mellitus, preoperative leuprorelin or relugolix use, history of previous cesarean delivery, additional surgical procedures (salpingo‐oophorectomy or ovarian cystectomy performed at the time of hysterectomy), the presence of endometriosis, rASRM stage, and the presence of cul‐de‐sac obliteration. We also collected data regarding surgical outcomes, including operative time, intraoperative blood loss, superficial and deep incisional surgical site infection (SSI), organ/space SSI, bowel injury, urologic complications, and deep venous thrombosis (DVT). The definition of SSI was based on the Centers for Disease Control and Prevention (CDC) criteria [7]. Cefmetazole was used for surgical prophylaxis and was administered at a dose of 1 g, 30 min before skin incision, followed by repeated doses every 3 h; in patients weighing ≥ 80 kg, a dose of 2 g was administered per dose. A uterine manipulator was used in all cases. 2.2. Statistical Analyses Propensity scores were estimated using a logistic regression model with 1:1 patient matching and a caliper distance of 0.20. The following baseline characteristics were included in the propensity score model: age, BMI, obesity, diabetes mellitus, previous cesarean delivery, preoperative leuprorelin or relugolix use, and the weight of the resected specimen. We compared baseline characteristics and surgical outcomes between the two groups before and after propensity score matching (PSM). Differences in continuous variables were assessed using the Mann–Whitney U test. Differences in categorical variables were assessed using Fisher's exact test or the chi‐squared test, as appropriate. p value of < 0.05 was considered statistically significant. To evaluate the association between endometriosis and the risk of complications (superficial and deep incisional SSI, organ/space SSI, bowel injury, urologic complications, and deep venous thrombosis), univariate and multivariable logistic regression analyses were performed. The results are presented as odds ratios (ORs) with 95% confidence intervals (CIs). Statistical analyses were performed using EZR (Saitama Medical Center, Jichi Medical University, Saitama, Japan), which is a graphical user interface for R software (The R Foundation for Statistical Computing, Vienna, Austria). More precisely, it is a modified version of R Commander designed to add statistical functions frequently used in biostatistics [8]. 3. Results 3.1. Baseline Characteristics of the 836 Patients The baseline characteristics of these 836 patients are shown in Table 1. The median age of the 836 patients was 46 years (IQR: 43–49). Fifty of the 836 patients (6.0%) were obese, 27 patients (3.2%) had diabetes mellitus, 97 patients (11.6%) had a previous history of cesarean delivery, and preoperative leuprorelin or relugolix was used in 318 of the 836 patients (38.0%). Of the 836 patients, 115 (13.8%) had endometriosis, and cul‐de‐sac obliteration was confirmed in 50 patients (6.0%) during surgery. TABLE 1. | N = 836 | | |---|---| | Age (years old), median [IQR] | 46 [43–49] | | Parity | | | No | 162 (19.4) | | Yes | 617 (73.8) | | Unknown | 57 (6.8) | | Obesity (BMI ≥ 30) | | | No | 786 (94.0) | | Yes | 50 (6.0) | | Diabetes mellitus | | | No | 809 (96.8) | | Yes | 27 (3.2) | | Preoperative leuprorelin or relugolix use | | | No | 518 (62.0) | | Yes | 318 (38.0) | | Leuprorelin | 192 | | Relugorix | 126 | | Previous cesarean delivery | | | No | 739 (88.4) | | Yes | 97 (11.6) | | Salpingo‐oophorectomy at the timing of hysterectomy | | | Not performed | 694 (83.0) | | Unilateral | 90 (10.8) | | Bilateral | 52 (6.2) | | Ovarian cystectomy at the timing of hysterectomy | | | Not performed | 802 (95.9) | | Unilateral | 31 (3.7) | | Bilateral | 3 (0.4) | | Endometriosis | | | No | 721 (86.2) | | Yes | 115 (13.8) | | Cul‐de‐sac obliteration | | | No | 786 (94.0) | | Yes | 50 (6.0) | | rASRM stage | | | 0 | 721 (86.2) | | 1 | 2 (0.2) | | 2 | 8 (1.0) | | 3 | 41 (4.9) | | 4 | 64 (7.7) | Abbreviations: BMI: body mass index; IQR: interquartile range; rASRM stage: revised American Society for Reproductive Medicine stage. 3.2. Patient Characteristics Before and After PSM Patient characteristics between patients with and without endometriosis before and after PSM are shown in Table 2. Before PSM, the median age, median BMI, the proportion of patients with diabetes mellitus, the proportion of patients with previous cesarean delivery, and the proportion of patients with preoperative leuprorelin or relugolix use were not statistically different between the two groups. The median weight of the resected specimen in the non‐endometriosis group was significantly larger than that in the endometriosis group (290 vs. 234 g, p = 0.001). After PSM, 115 patients with endometriosis and 115 patients without endometriosis were successfully matched, and there were no significant differences in baseline characteristics between the two groups (Table 2). TABLE 2. | Before PSM | After PSM | ||||| |---|---|---|---|---|---|---| | No endometriosis, n = 721 | Endometriosis, n = 115 | p | No endometriosis, n = 115 | Endometriosis, n = 115 | p | | | Median age, years old [IQR] | 46 [43–49] | 46 [44–48] | 0.834 | 46 [43–48] | 46 [44–48] | 0.288 | | Median BMI, kg/m2 [IQR] | 22.1 [20.3–24.7] | 22.0 [20.3–24.9] | 0.936 | 22.2 [20.2–24.6] | 22.0 [20.3–24.9] | 0.965 | | Obesity (BMI ≥ 30) (%) | |||||| | No | 678 (94.0) | 108 (93.9) | 1.000 | 110 (95.7) | 108 (93.9) | 0.768 | | Yes | 43 (6.0) | 7 (6.1) | 5 (4.3) | 7 (6.1) | || | Diabetes mellitus (%) | |||||| | No | 697 (96.7) | 112 (97.4) | 1.000 | 111 (96.5) | 112 (97.4) | 1.000 | | Yes | 24 (3.3) | 3 (2.6) | 4 (3.5) | 3 (2.6) | || | Previous cesarean delivery (%) | |||||| | No | 635 (88.1) | 104 (90.4) | 0.533 | 105 (91.3) | 104 (90.4) | 1.000 | | Yes | 86 (11.9) | 11 (9.6) | 10 (8.7) | 11 (9.6) | || | Preoperative leuprorelin or relugolix use (%) | |||||| | No | 445 (61.7) | 73 (63.5) | 0.757 | 71 (61.7) | 73 (63.5) | 0.892 | | Yes | 276 (38.3) | 42 (36.5) | 44 (38.3) | 42 (36.5) | || | Weight of the resected specimen (g), median [IQR] | 290 [183–482] | 234 [155–326] | 0.001 | 240 [142–339] | 234 [155–326] | 0.625 | Abbreviations: BMI: body mass index; IQR: interquartile range; PSM: propensity score matching. 3.3. Surgical Outcomes Before and After PSM Surgical outcomes between patients with and without endometriosis before and after PSM are shown in Table 3. Before PSM, the median operative time in patients with endometriosis was significantly longer than that in patients without endometriosis (218 vs. 174 min, p < 0.001). Superficial and deep incisional SSI were more frequently observed in patients with endometriosis compared with those without endometriosis (4.3% vs. 1.2%, p = 0.032). Patients with endometriosis had a significantly higher incidence of organ/space SSI compared with those without endometriosis (15.7% vs. 3.9%, p < 0.001). The incidence of bowel injury was also significantly higher in patients with endometriosis than in those without (3.5% vs. 0.3%, p = 0.004). In contrast, there were no significant differences in the incidence of urologic complications or DVT between the two groups. After PSM, the median operative time in patients with endometriosis was significantly longer than that in patients without endometriosis (218 vs. 164 min, p < 0.001). Patients with endometriosis had a significantly higher incidence of organ/space SSI compared with those without endometriosis (15.7% vs. 6.1%, p = 0.032) (Table 3), with an OR of 2.860 (95% CI: 1.15–7.15) (Table 4). In contrast, there were no significant differences in the incidence of superficial and deep incisional SSI, bowel injury, urologic complications, or DVT between the two groups (Table 3). TABLE 3. | Before PSM | After PSM | ||||| |---|---|---|---|---|---|---| | No endometriosis, n = 721 | Endometriosis, n = 115 | p | No endometriosis, n = 115 | Endometriosis, n = 115 | p | | | Operative time (minutes), median [IQR] | 174 [144–206] | 218 [167–264] | < 0.001 | 164 [135–195] | 218 [167–264] | < 0.001 | | Superficial and deep incisional SSI (%) | |||||| | No | 712 (98.8) | 110 (95.7) | 0.032 | 113 (98.3) | 110 (95.7) | 0.446 | | Yes | 9 (1.2) | 5 (4.3) | 2 (1.7) | 5 (4.3) | || | Organ/space SSI (%) | |||||| | No | 693 (96.1) | 97 (84.3) | < 0.001 | 108 (93.9) | 97 (84.3) | 0.032 | | Yes | 28 (3.9) | 18 (15.7) | 7 (6.1) | 18 (15.7) | || | Bowel injury (%) | |||||| | No | 719 (99.7) | 111 (96.5) | 0.004 | 113 (98.3) | 111 (96.5) | 0.683 | | Yes | 2 (0.3) | 4 (3.5) | 2 (1.7) | 4 (3.5) | || | Urologic complication (%) | |||||| | No | 712 (98.8) | 112 (97.4) | 0.221 | 115 (100) | 112 (97.4) | 0.247 | | Yes | 9 (1.2) | 3 (2.6) | 0 (0) | 3 (2.6) | || | Deep venous thrombosis (%) | |||||| | No | 720 (99.9) | 114 (99.1) | 0.256 | 115 (100.0) | 114 (99.1) | 1 | | Yes | 1 (0.1) | 1 (0.9) | 0 (0.0) | 1 (0.9) | Abbreviations: IQR: interquartile range; PSM: propensity score matching; SSI: surgical site infection. TABLE 4. | Before PSM | After PSM | ||| |---|---|---|---|---| | OR | 95% CI | OR | 95% CI | | | Superficial or deep incisional SSI | |||| | No | 1 | 1 | || | Yes | 3.600 | 1.180–10.90 | 2.570 | 0.488–13.50 | | Organ/space SSI | |||| | No | 1 | 1 | || | Yes | 4.590 | 2.450–8.620 | 2.860 | 1.15–7.15 | | Bowel injury | |||| | No | 1 | 1 | || | Yes | 13.0 | 2.350–71.60 | 2.04 | 0.365–11.30 | | Urologic complication | |||| | No | 1 | NE | || | Yes | 2.12 | 0.565–7.950 | || | Deep venous thrombosis | |||| | No | 1 | NE | || | Yes | 6.32 | 0.392–102.0 | Abbreviations: CI: confidence interval; NE: not evaluated; OR: odds ratio; PSM: propensity score matching; SSI: surgical site infection. 4. Discussion In the current study, the impact of endometriosis on surgical outcomes in patients undergoing TLH for benign diseases was investigated using propensity score‐matched analysis. We found that the operative time in patients with endometriosis was significantly longer and that patients with endometriosis had a significantly higher incidence of organ/space SSI, compared with those without endometriosis. A previous study showed that the incidence of postoperative complications was higher in patients with endometriosis, with an OR of 1.25 (95% CI 1.17–1.34) [3]. Another retrospective cohort study using American College of Surgeons NSQIP data [9] revealed that patients with endometriosis were more likely to develop deep incisional SSI and organ/space SSI. On the other hand, there were no significant differences in the incidence of superficial SSI, sepsis, deep venous thrombosis, or reoperation between patients with and without endometriosis [9]. Although no randomized controlled trials have compared surgical outcomes of TLH between patients with and without endometriosis, the available retrospective studies, taken together, suggest that patients with endometriosis may be at increased risk of developing SSI. Endometriosis is known to be associated with an increased risk of PID or TOA [5]. It has been suggested that retained blood within endometriotic cysts and at other sites in the peritoneal cavity provides an ideal medium for bacterial growth, thereby facilitating infection. Intraoperative rupture of endometriotic cysts may therefore influence the incidence of organ/space SSIs. Therefore, PID and TOA occur more frequently in women with endometriosis than in those without endometriosis, suggesting that endometriosis may serve as a potential source (or nidus) of pelvic infection. Although the Cochrane review found insufficient evidence to conclude that any particular antibiotic regimen was superior for hysterectomy [10], cefazolin is recommended according to the ACOG practice bulletin [11], and cefazolin or second‐generation cephalosporins are recommended in gynecologic surgery based on Japanese guidelines [12]. Cephalosporins are highly effective against skin flora; for example, Streptococcus spp., Staphylococcus aureus , and coagulase‐negative staphylococci [13]. Skin bacteria constituted 28.9% of the causative pathogens in superficial incisional SSIs, whereas in organ/space SSIs, their proportion was only 6.0%, with intestinal or vaginal bacteria—such as Bacteroides spp., Enterococcus spp., Escherichia coli , Pseudomonas aeruginosa , and other anaerobes—accounting for 60.7% [14]. Cefazolin, recommended as prophylactic antibiotic choice in both the United States and Japan, lacks activity against P. aeruginosa , and second‐generation cephalosporins other than cefmetazole are ineffective against anaerobic bacteria. Cephalosporins also lack activity against Enterococcus spp. We found that a high incidence of organ/space SSIs was observed in patients with endometriosis, which may be attributable to the fact that the spectrum of antibiotics administered intraoperatively did not cover the causative organisms. Based on the recent literature, the addition of metronidazole to cephalosporin prophylaxis during hysterectomy may reduce the risk of SSIs [15, 16]. The present study has several limitations. First, the data used in this study were retrospective, and the sample size was relatively small. Larger studies are needed to validate our findings. Second, bacterial cultures obtained at the time of diagnosis of organ/space SSIs were not available for all patients. Consequently, we could not assess whether the antimicrobial agents administered intraoperatively adequately covered the causative pathogens. Third, preoperative assessment for bacterial vaginosis, a known risk factor for organ/space SSI, was not performed. In addition, the association between intraoperative cyst rupture and the incidence of SSI could not be evaluated. Furthermore, the diagnosis of endometriosis was based on intraoperative findings or histopathological examination and was not standardized across all cases due to the retrospective nature of the study. This heterogeneity in diagnostic criteria may have introduced misclassification bias. Finally, data on preoperative progestin use, including dienogest, were not collected in this study, which may limit the generalizability of our findings regarding preoperative hormonal therapy. In conclusion, we conducted a retrospective study to evaluate the impact of endometriosis on perioperative outcomes in patients undergoing TLH for benign diseases using propensity score–matched analysis. Compared with patients without endometriosis, patients with endometriosis were at increased risk of organ/space SSI. Author Contributions All authors are in agreement with the content of the manuscript. Y.T.: manuscript writing/editing, conceptualization of the study, data analysis, data collection, operating surgeon. A.O.: manuscript reviewing, operating surgeon. T.I.: manuscript reviewing, operating surgeon. Y.S.: manuscript reviewing, operating surgeon. Conflicts of Interest The authors declare no conflicts of interest. Acknowledgments The authors have nothing to report. Data Availability Statement The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

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