Clinical evaluation and management of endometriosis: 2024 guideline for Korean patients from the Korean Society of Endometriosis

Endometriosis, a prevalent but debilitating condition affecting women, poses significant challenges in diagnosis and management. Although international guidelines exist, the unique clinical presentations and healthcare landscape in Korea necessitate tailored recommendations. The current 2024 guideline, developed by the Korean Society of Endometriosis (KSE), builds upon the 2018 KSE guideline and incorporates the latest evidence-based research and expert consensus to provide clinicians with comprehensive, up-to-date guidance [ 1 ]. This guideline addresses key areas such as diagnosis, medical and surgical management, considerations for special populations, and its complex relationship with cancer. The recommendations are categorized based on the strength of evidence using the grading of recommendations, assessment, development, and evaluations framework, and the details are described in Table 1 .

Surgical intervention may be considered for the reduction of endometriosis-associated pain (grade A). Excising endometriotic lesions is more effective than draining or ablating them in terms of pain and symptom reduction, as well as recurrence prevention (grade B). Laparoscopy is recommended as the standard surgical method [ 30 ]. Compared to laparotomy, laparoscopic surgery has advantages, such as reduced pain, shorter hospitalization, and cosmetic aspects [ 31 ]. Compared to laparotomy, it also has the same effect on endometriosis pain [ 32 ]. Regarding robotic surgery, there was no difference in surgical results, but the robotic approach showed longer operation time compared to conventional laparoscopic surgery in certain situations [ 33 ]. Further studies are required to evaluate the cost-effectiveness of various surgical techniques. Cystectomy is more effective than drainage or ablation in reducing recurrence rates and endometriosis-associated pain during the surgical treatment of ovarian endometriomas (grade B). Minimizing ovarian damage is crucial during surgical intervention for ovarian endometriomas (grade A). Preoperative assessment of Anti-Müllerian hormone levels should be considered in cases of large, recurrent, or bilateral endometriomas in women who desire future pregnancy due to the increased risk of ovarian damage (grade D). Surgical removal of large ovarian endometriomas (≥3 cm) is more effective than drainage or electrocoagulation for alleviating symptoms and preventing recurrence [ 34 - 36 ]. In addition, histological diagnosis is possible when a cystectomy is performed [ 35 ]. Surgical excision of DE can reduce endometriosis-associated pain and improve the quality of life (grade B) [ 37 , 38 ]. Clinicians should consider referrals to tertiary care institutions to minimize complications during surgery, which often requires multidisciplinary expertise (grade D). Considering hysterectomy for severe, treatment-resistant endometriosis pain in women who do not wish to conceive or if other uterine pathologies exist is a viable treatment option (grade D). Following hysterectomy and bilateral oophorectomy for the treatment of endometriosis, continuous combined estrogen-progestogen hormone therapy (HT) is recommended for the management of menopausal symptoms (grade C). Tibolone may be considered as a second-line option for patients who are unable to use continuous combined estrogen-progestogen HT (grade D). The decision to perform bilateral oophorectomy with hysterectomy should be carefully considered. Thorough patient discussions should be held before surgery, explaining that the probability of pain persisting after hysterectomy is about 15% and that there is a 3-5% risk of worsening pain or developing new symptoms [ 39 ]. Pain after hysterectomy may be due to ovarian remnant syndrome. Preoperative hormonal treatment, compared to surgery alone, is not recommended for pain management in women with endometriosis, as it does not provide significant benefits on the pain and/or recurrence reduction rate in the postoperative period (grade A) [ 40 ]. Postoperative hormonal treatment includes short-term (less than 6 months) and long-term (6 months or more) treatment, and long-term treatment aims to prevent recurrence (grade D). In women who are not planning to become pregnant, postoperative hormonal treatment may be considered for the management of endometriosis-associated pain (grade C) [ 40 ].

Detailed history taking and physical examination are crucial to prevent delayed diagnosis, as patients may endure the disease for years before diagnosis [ 2 , 3 ]. Imaging studies, such as pelvic ultrasound and magnetic resonance imaging (MRI), are also notably accurate for endometriosis diagnosis. Therefore, international societies, including the European Society for Reproductive Medicine, have recommended that ovarian endometrioma and deep endometriosis (DE) be diagnosed solely upon imaging findings, excluding diagnostic laparoscopy [ 4 ]. Endometriosis should be suspected in women of childbearing age presenting with gynecological symptoms, including menstrual pain, pelvic pain, dyspareunia, fatigue, and infertility (grade D) [ 5 ]. Endometriosis should be considered in women of childbearing age with dyschezia, dysuria, painful rectal bleeding or hematuria, periodic swelling/pain at the surgical site, and cough/hemoptysis/chest pain/shoulder pain/catamenial pneumothorax (grade D) [ 5 ]. Pelvic and abdominal examinations should be performed in all patients with suspected endometriosis. This examination can be conducted at any point during the menstrual cycle (grade D) [ 6 ]. Painful nodules near the rectum, vagina, or fornix during a physical examination may indicate DE (grade C). Palpation of an ovarian mass during pelvic examination in women with suspected endometriosis suggests an ovarian endometrioma (grade C). Endometriosis cannot be excluded in women with suspected endometriosis, even with normal physical examination results. Additional tests, mostly based on imaging, should be considered (grade B) [ 7 ]. There is insufficient evidence regarding the use of biomarkers from endometrial tissue, blood, menstrual blood, and uterine fluids for diagnosing endometriosis (grade A) [ 8 ]. Further research is needed on biomarkers for endometriosis recurrence (grade C). For suspected endometriosis, transvaginal or transrectal ultrasound is recommended as the initial step to confirm or exclude ovarian endometrioma (grade A) [ 9 ]. For signs or symptoms of endometriosis, transvaginal or transrectal ultrasound may help confirm or exclude DE involving the sigmoid colon and rectum (grade A) [ 10 ]. If DE is suspected, especially involving the ureters, bladder, or intestines, additional imaging such as MRI should be considered (grade D). Even if imaging studies, such as pelvic ultrasound and MRI, appear normal, endometriosis cannot be excluded (grade D). In women with suspected endometriosis, empirical medical treatment, such as gonadotropin-releasing hormone (GnRH) agonists, progestins, and combined oral contraceptives (COC), may be initiated following imaging, regardless of imaging confirmation of endometriosis (grade D) [ 10 ]. After imaging studies are conducted on women with suspected endometriosis, diagnostic laparoscopy can be performed for lesion removal and pathological confirmation. Both empirical medical therapy and diagnostic laparoscopy are viable options for managing the condition. Currently, no evidence indicates which approach is more effective, and decisions can be made through patient discussion (grade D) [ 1 ]. Women with endometriosis, especially deep or ovarian cases, require close follow-upcare (grade D). Cancer antigen-125 (CA-125) exhibits low sensitivity but a high positive predictive value, making it a potential option for follow-up monitoring during treatment (grade D) [ 8 ].

The current 2024 guideline represents a significant advancement in the clinical evaluation and management of endometriosis for Korean patients. By integrating the latest research findings and expert consensus, this guideline offers comprehensive recommendations tailored to the specific needs of the Korean population. While acknowledging the limitations of existing evidence, this guideline emphasizes a patient-centered approach, advocating for shared decision-making and personalized treatment plans. Further research and collaboration in Korea will enhance endometriosis care and improvewomen’slives.

Endometriosis can induce infertility through various mechanisms, and studies on treatments for endometriosis-associated infertility, including medical, surgical, and non-medical therapies, have been conducted to enhance natural conception rates [ 58 - 60 ]. For mild-revised American Society for Reproductive Medicine (rASRM) stage I/II-endometriosis-associated infertility, surgery may be considered to increase natural conception rates. Concerning pregnancy rates, laparoscopic surgery is superior to diagnostic laparoscopy (grade A) [ 58 - 60 ]. In severe-rASRM stage III/IV-endometriosis, laparoscopic surgery demonstrates higher natural conception rates than expectant management (grade A) [ 61 , 62 ]. There is no definitive evidence that laparoscopic surgery improves fertility in DE. However, among patients experiencing clinical symptoms such as dyschezia who desire pregnancy, it can be considered a treatment option (grade D) [ 58 - 62 ]. When deciding on surgery, factors such as the presence of pain, patient’s age, surgical history, presence of other infertility factors, and ovarian reserve should be considered (grade D). To increase natural conception rates, ovarian cystectomy may be considered over other surgical methods, such as drainage or ablation (grade A) [ 63 - 65 ]. It is important to be cautious, as ovarian reserve may diminish during surgery, potentially impacting future pregnancy rates (grade B) [ 66 ]. The endometriosis fertility index can be used to counsel patients regarding the possibility of natural conception without the need for ART after surgery for endometriosis (grade D) [ 67 ]. In women with endometriosis-related infertility, the use of ovarian suppression therapy, such as GnRH agonists, progesterone, or COCs, is not recommended for improving fertility (grade A) [ 68 - 70 ]. Hormonal suppression therapy following surgery for endometriosis is not recommended for increasing pregnancy rates (grade A) [ 68 ]. Women who do not immediately attempt pregnancy after surgery or those who seek pain relief or aim to prevent recurrence may consider hormonal therapy following surgery for endometriosis (grade B) [ 69 ]. Using letrozole for purposes other than ovulation induction, as well as other anti-inflammatory medications, is not recommended for improving natural pregnancy rates in infertile women with endometriosis (grade A) [ 70 ]. The provision of specific nutrients or the application of non-medical alternative therapies is not recommended for infertile women with endometriosis (grade D). There is no reliable evidence supporting the efficacy of non-medical methods, such as diet, Chinese medicine, electrotherapy, acupuncture, physiotherapy, exercise, and psychological interventions, to increase the likelihood of pregnancy in women with endometriosis; therefore, they are not recommended.

Endometriosis shares characteristics with cancer, including chronic inflammation, resistance to cell death, tissue invasion, and the presence of local and distant lesions [ 123 , 124 ]. Research is ongoing to understand its association with cancer and to develop early detection methods. Concerns arise regarding the cancer risk linked to hormone therapy and the uncertain effect of surgery on ovarian cancer risk in patients with endometriosis. Endometriosis does not have a high overall cancer risk but is linked to ovarian, breast, and thyroid cancers, although the absolute increase in risk compared to the general population is minimal (grade A). Clinicians should inform women that endometriosis does not significantly increase the risk of ovarian, breast, or thyroidcancers (grade D). More data are needed to predict if endometriosis will progress to cancer. Until clear risk factors for ovarian cancer in patients with endometriosis are identified, proactive measures, such as surgical oophorectomy, are not recommended (grade D). Endometriosis is associated with a relatively increased ovarian cancer risk, particularly clear-cell and endometrioid carcinomas [ 125 - 127 ]. Two meta-analyses reported that the relative risk of cervical cancer is low in women with endometriosis ( Table 2 ) [ 127 , 128 ]. Recent meta-analyses report that endometriosis increases the relative risk of breast cancer [ 128 , 129 ], particularly among individuals aged over 50 [ 130 , 131 ]. In a meta-analysis of five studies, endometriosis was reported to increase the thyroid cancer risk [ 128 ]. A meta-analysis of seven studies explored the link between endometriosis and melanoma and found no association, although only two studies concerning basal cell carcinoma were included, with an increased risk reported [ 128 ]. Additional research is required to fully understand these associations. Risk estimates derived from recent meta-analytic data indicating elevated risks for ovarian cancer (summary relative risks [SRR], 1.93), breast cancer (SRR, 1.04), and thyroid cancer (SRR, 1.39) among women with endometriosis demonstrate that while these relative risks are higher, the absolute risks remain notably low compared to the general population ( Table 3 ) [ 128 , 132 ]. Clinicians are advised to reassure women with endometriosis that despite the association with certain cancers, such as ovarian, breast, and thyroid cancer, their absolute cancer risk is minimal and akin to that of women without endometriosis [ 132 ]. Factors predicting progression to ovarian cancer include the association of endometrioma with an increased risk, whereas superficial and DE show no such correlation [ 133 ]. Studies offer limited evidence regarding the predictive value of somatic mutations in DE in ovarian cancer [ 128 ]. Serum CA-125 testing or imaging, commonly used for ovarian malignancy surveillance in women with endometriosis, lacks clear efficacy according to randomized controlled trials [ 134 , 135 ]. In one study, the predictive risk factors for ovarian cancer in patients with endometriosis included increasing age, menopausal status, elevated CA-125 levels, large endometrioma (>9 cm), and long-term endometriosis (>5 years) [ 136 ]. However, further longitudinal analyses are necessary to confirm these predictions and establish definitive risk factors for ovarian cancer in this population. Clinicians should inform and reassure women with endometriosis regarding the risk of malignant tumors when using oral contraceptives for pain management or preventing recurrence (grade D) [ 3 , 137 , 138 ]. Complete removal of endometriosis and endometrioma-containing ovaries can reduce ovarian cancer risk. However, the treatment method must be decided considering the disadvantages of surgery (surgery-related complications, pain, decreased ovarian function, etc.) (grade D) [ 139 , 140 ]. Women with endometriosis should not undergo additional testing beyond the current cancer screening protocols (grade D). For individuals with additional risk factors, such as specific gene mutations or family history, cancer screening may be warranted following individualized guidelines (grade D).