Age of diagnosis with endometriosis and potential predicting factors: A single-center cross-sectional study

Endometriosis is a prevalent disease affecting 10–15% of reproductive-age female patients, with an average delay in diagnosis of 8–12 years [ 1 ]. It is defined as a systemic inflammatory disease caused by the presence of endometrial-like tissue in extra-uterine sites [ 2 ]. Several risk factors have been associated with endometriosis, including early age at menarche and a family history of the disease [ 1 , 3 ]. Tamoxifen, which acts as an estrogen agonist in the endometrium, has also been reported in association with endometriosis, although its pathophysiology remains incompletely understood [ 4 ]. Due to diagnostic delays and lack of effective medical treatment options, research indicates that this disease represents a notable burden within the spectrum of benign gynecological conditions among patients in their reproductive years [ 5 ]. Clinically, endometriosis can manifest through a range of symptoms. Dysmenorrhea is the most reported symptom that suggests the presence of endometriosis, but many other manifestations exist including but not limited to urinary and bowel symptoms, dyspareunia, infertility, and chronic pelvic pain [ 6 ]. The existing literature on endometriosis has little generalizability to the Middle East & North Africa (MENA) population due to a huge knowledge gap relating to all aspects of this disease. A systematic review done by Moussa et al. estimated the prevalence of surgically confirmed endometriosis in the Middle East and Persian region to be 12.9% in women undergoing laparoscopy for any indication [ 7 ]. As for Lebanon, the most recent clinical study on patients with endometriosis was a retrospective case-control study of patient records at the American University of Beirut Medical Center (AUBMC) between 1979 and 1981 showing that this disease represented 2% and 21% of all gynecological cases and laparoscopic cases respectively [ 8 ]. In the current landscape, a singular large-scale case-control study conducted in the United Arab Emirates (UAE) stands out as it provides a detailed account of symptoms among 518 Arab endometriosis patients. However, it is noteworthy that this study does not encompass certain endometriosis-related symptoms, including dyspareunia, as well as urinary and bowel symptoms unrelated to dysuria and dyschezia respectively. Notably, their investigation reveals an average diagnostic delay of 11.61 years, a figure that escalates to 15.81 years in females who are not married, but no further investigation is done to evaluate for predictors of diagnostic delay [ 9 ]. This disparity may reflect sociocultural barriers to seeking gynecologic care, particularly among unmarried women, and hesitancy to seek evaluation for menstrual or pelvic symptoms. Our study aims to characterize the behavioral and clinical features of patients with endometriosis at the largest tertiary healthcare center in Lebanon, the American University of Beirut Medical Center (AUBMC), and to identify predictors of age at diagnosis. Specifically, we examine the impact of symptom severity, age at menarche, sexual activity, and infertility on the age of diagnosis. Given the scarcity of regional data and the persistent global challenge of diagnostic delay, identifying these predictors is essential for informing strategies to improve patient care and reduce delays in diagnosis.

As shown in Table 1 , the mean age of the 688 patients included in the study was 38.42 years (SD = 8.47) and the range was 20–72 years. A healthy BMI was observed in 68.3% of patients; 55.7% reported never smoking, and 63.1% reported no alcohol use. The mean age at menarche was 12.25 years (SD = 1.03), and 77.5% of patients had engaged in sexual activity prior to diagnosis. The mean age at endometriosis diagnosis was 29.67 years (SD = 6.23) with a range of 14–52 years, and the mean follow-up duration was 4.74 years with a range of [1–28] years. Table 2 presents the prevalence of each endometriosis symptom in our cohort. Dysmenorrhea was reported in 75.7% of patients, while chronic pelvic pain or acyclical pain was reported in 48.5%. Dyspareunia was reported in 25.1% of patients, and neuropathic pain was the least prevalent of all symptoms (8.7%). Furthermore, only 2 of the 688 patients were referred to a pain center to manage their symptoms, and 164 patients were admitted to the ER due to endometriosis symptoms, with a mean of 2.3 admissions per patient. Heavy bleeding was documented in the charts of 178 patients (25.9%), out of whom 97 (54.5%) had a diagnosis of fibroids or adenomyosis. Lastly, 279 out of 688 patients (40.6%) experienced infertility, accounting for 65.9% of those actively trying to conceive. In Table 3 , we divided patients into 4 groups based on the severity of symptoms determined by SSS . 45.2% of patients had none of the three severe symptoms, 31% presented with SSS = 1, 20.1% had SSS = 2, while 3.8% had all three symptoms considered severe. In Table 4 , the one-way ANOVA test shows an overall significant difference in the age of diagnosis among the 4 SSS groups with p-value = 0.006 . Post Hoc testing for multiple comparisons via the LSD method showed a significant pairwise difference between SSS = 0 & SSS = 1 , and between SSS = 1 & SSS = 2 . In particular, patients with 1 severe symptom were diagnosed earlier than patients presenting with no severe symptoms by 1.87 years ( p-value = 0.001 ), while patients with 2 severe symptoms were diagnosed later by 1.36 years compared to patients with 1 severe symptom ( p-value = 0.045 ). Table 5 summarizes the results of the multiple linear regression analysis performed to examine the association between the value of SSS and the mean age of diagnosis, while adjusting for age of menarche, sexual activity, and infertility as covariates. A trend can be seen where patients presenting with more severe symptoms are diagnosed earlier than those presenting with no severe symptoms, yet this is only significant for patients with SSS = 1 diagnosed earlier by 2.12 years (p < 0.001) , and for patients whose SSS = 2 diagnosed 1.72 years earlier compared to patients with no severe symptoms (p < 0.001) . To note, patients with the most severe presentation ( SSS = 3 ) had an earlier diagnosis by one and half years but this result was not significant. In addition to that, sexually active patients had a delayed diagnosis of 4.74 years (p < 0.001) compared to non-sexually active patients, while patients with infertility were diagnosed earlier by 2.72 years (p < 0.001) compared to others, when controlling for the severity of the symptoms.

Endometriosis is a systemic disease characterized by a range of symptoms that healthcare professionals should be knowledgeable about to foster accurate suspicion. Patients with endometriosis who present with infertility and up to two severe symptoms tend to receive an earlier diagnosis than those with no symptoms. However, the age of diagnosis is not significantly different for patients who report all three endometriosis pain symptoms (CPP, Dyspareunia, and Neuropathic pain). These study findings suggest that the severity of symptoms is not always a reliable indicator of early diagnosis, highlighting the need for increased awareness of the clinical presentation of this condition among both the public and healthcare professionals. By doing so, we can reduce delays in diagnosis and facilitate earlier treatment for the condition.

In this retrospective cross-sectional study, we employed convenience sampling; we included patients of all ages diagnosed with or treated for endometriosis who presented to AUBMC over one year between 01/11/2018 and 31/10/2019, with medical records indicating a suspected clinical diagnosis of endometriosis or a confirmed endometriosis diagnosis based on imaging or surgical findings. Patients with abdominal wall endometriosis related to prior cesarean section without evidence of pelvic disease, as well as patients initially suspected to have endometriosis but subsequently found to have no evidence of disease on imaging or surgery, were excluded. After applying these criteria, a total of 688 patients were included; of these, 17 patients were diagnosed based on documented clinical pain symptoms particularly dysmenorrhea, while the remaining patients had confirmation through imaging, surgery, or both. As the largest tertiary center in Lebanon, AUBMC receives patients from across the country, enhancing the representativeness of our sample for the general Lebanese population. The combination of convenience sampling from a diverse patient population and the application of clearly defined exclusion criteria helped minimize selection bias and support the generalizability of our findings. All variables were tabulated and presented depending on their scale: categorical variables were summarized using frequencies and percentages; while continuous variables were summarized in terms of means, medians, range, and standard deviations (SD). Missing data were present only in continuous variables and ranged from 6% to 9% across variables. Given the relatively low proportion of missing values, missing observations were replaced with the mean of the corresponding variable calculated from available cases to retain the full analytic sample. To address the research questions, we extracted data on behavioral and clinical characteristics of endometriosis patients, as well as potential predictors of age of endometriosis diagnosis. Table 1 presents behavioral characteristics including smoking, alcohol intake, sexual activity, in additional to age of menarche, age at diagnosis with endometriosis and follow-up period. Table 2 shows a detailed distribution of endometriosis-related symptoms among patients, as documented in gynecologist clinical notes at the time of patient presentation. Chronic Pelvic Pain (CPP) is defined as the presence of pain in the pelvis outside of menstruation for at least 6 months [ 10 ], while neuropathic pain is caused by a lesion or disease of the somatosensory system [ 11 ]. Symptoms of neuropathic pain may be variable, described in our population as burning or shooting pain often radiating to the legs or groin based on clinical documentation in the medical records. Infertility is defined as the inability to conceive after one year of trying for individuals under 35 or six months for those over 35. In addition to the symptoms, Table 2 also displays the number of patients referred to a pain center for pain symptoms, and the number of ED admissions at AUBMC due to endometriosis-related manifestations. Due to the absence of a validated scoring system for symptom severity, we utilized a Symptom Severity Score (SSS) ranging from 0 to 3, as detailed in Table 3 . This composite score is a simplified measure reflecting the number of key pain-related symptoms - chronic pelvic pain (CPP), dyspareunia, and neuropathic pain – that impact patients’ quality of life, rather than the intensity or severity of each symptom. It is important to note that patients with an SSS of 0 may still have other endometriosis-related symptoms not captured within this score. a Neuropathic pain: present in the records or described as burning or shooting pain, radiating to the legs or groin. b Gastrointestinal symptoms include bloating, IBS-like symptoms, pain during defecation, blood in stools, and tenesmus. c Urinary Symptoms include recurrent urinary tract infections, urinary frequency & urgency, and dysuria. d 164 (23.8%) were admitted to ER at AUBMC for endometriosis symptoms. a SSS (Symptom Severity Score) = CPP (Chronic Pelvic Pain) + Dyspareunia + Neuropathic Pain; Range [0–3]. This retrospective cross-sectional study received IRB approval on January 17, 2022. The IRB waived consent since the research project was classified as “minimal risk.” No patient was contacted. Between 17/01/2022 and 31/08/2023, data was extracted from the EPIC EMR database at AUBMC, implemented in November 2018. The study investigators de-identified the data before its inclusion in the database. To determine the difference in age of diagnosis with endometriosis between subgroups of endometriosis patients having different severity of symptoms as per the SSS , we performed one-way analysis of variance ( ANOVA ), followed by Post Hoc analysis for multiple comparisons using the Least Significant Difference ( LSD ) method ( Table 4 ). a p-value ≤ 0.05 is considered significant. b LSD: Least Significant Difference for multiple comparison testing c SSS (Symptom Severity Score) = CPP (Chronic Pelvic Pain) + Dyspareunia + Neuropathic Pain; Range [0–3]. We then conducted multiple linear regression analysis to determine the adjusted association between several predictors that included severity of symptoms, age of menarche, sexual activity, and infertility with the age of diagnosis as the outcome of interest ( Table 5 ). Given that endometriosis is classified as a gynecological disease and considering the substantial focus on fertility within our population, we accounted for factors that influence when patients seek medical assistance for endometriosis symptoms to consider their impact on the age of diagnosis. a p-value ≤ 0.05 is considered significant. b SSS = Symptom Severity Score. The level of significance was assumed to be ≤ 0.05. All analysis was conducted using STATA version 17 .