The effects of ethanol sclerotherapy on pain and quality of life in patients with endometrial cysts

Endometriosis is a chronic benign gynecological condition defined as the presence of endometrial tissue outside the uterine cavity, affecting approximately 10% of women of childbearing age. Based on the locations of the endometriotic ectopic implants, ovarian, peritoneal, and deep infiltrating subtypes of the disease can be distinguished. The endometriosis picture may involve both the isolated occurrence of such lesions as well as their coexistence. Lesions’ placement notwithstanding, the disease rarely remains asymptomatic, and most of the patients experience bothersome symptoms, including dysmenorrhea, chronic pelvic pain, dyspareunia, and infertility [1–3]. Such a broad spectrum of pain symptoms is the result of mild inflammation, altered pelvic anatomy, as well as changes within the central nervous system responsible for the modulation of pain sensation [3]. Endometriosis-related pain symptoms, besides rendering the disease a gynecological issue, elicit the prominent deterioration of patients’ psychological state [4]. Severe pain often exerts a negative effect on patients’ everyday functioning, deteriorates sexual intercourse, and aggravates social relationships. It not only impairs the quality of life but is additionally an economic burden due to the patients’ incapacity for work [5, 6]. Additionally, all these psychological ailments accompanying endometriosis are intensified by a frequent lack of diagnosis and delayed implementation of proper treatment regimens [7]. Although recently we have witnessed the redefining of endometriosis treatment schemes, pharmacotherapy and surgical treatment are still the mainstay of management [8]. In general, it has been proven that both these treatment pathways are effective in pain alleviation and improving the psychological condition of patients [9–11]. Nevertheless, despite such efficacy, they also display some limitations and can trigger negative psychological implications. Firstly, in more than one-fourth of patients resistant to hormonal treatment, in whom such treatment does not relieve pain, the impairment of their mental condition can be observed [12]. Secondly, surgery as an invasive procedure may, per se, lead to anxiety in patients and boost concerns about fertility, especially if ovarian surgery is performed [13]. Among alternative approaches offered to patients suffering from endometriosis, sclerotherapy is a beneficial tool in resolving ovarian endometrial cysts. This minimally invasive procedure involves aspirating the endometrial cyst content and injecting ethanol or other sclerosing agents into the cyst to sclerotize its wall [14]. Recent endeavors have predominantly focused on the clinical effects of sclerotherapy and evaluated the effectiveness of this method on endometrial cyst recurrences, in vitro fertilization outcomes, pregnancy outcomes, and potential complications. However, negligible reports regarding the impact of sclerotherapy on pain alleviation have been published [15, 16]. Moreover, none of the researchers has focused on the influence of this procedure on the quality of life.

We aimed to compare the sensation of chronic pelvic pain, menstrual pain, and pain accompanying sexual intercourse before and after sclerotherapy. In addition, this study has assessed the quality of life in patients undergoing the procedure and evaluated patients’ satisfaction.

The study was performed between 24 January 2023 and 31 March 2024. We included patients diagnosed with endometrial cysts who underwent transvaginal ultrasound-guided ethanol sclerotherapy at the Center of Reproductive and Minimally Invasive Gynecology of University Clinical Hospital No. 1, Lublin, Poland. Informed consent was obtained from all patients before starting the procedure. Sclerotherapy was performed in the lithotomy position, under sedation with the use of midazolam and propofol. The procedure was performed transvaginally under ultrasound control. First, the cyst content was aspirated and sent for cytological examination. The cyst cavity was flushed with saline until transparent fluid was obtained. Further, 96% ethanol was injected into the cyst at the ⅔ initial volume of the cyst and was aspirated after ten minutes. Data concerning the number of endometrial cysts, the volume of aspirated cyst contents, as well as the volume of instilled ethanol were recorded during the procedure. Approximately half an hour before the onset of sclerotherapy, patients filled out the first questionnaire in the paper version. All patients were informed about the purpose of the study and its anonymous character. The respondents were instructed on how to complete the questionnaire properly and they filled it out fully independently. We excluded patients who reported the occurrence of chronic diseases other than endometriosis. Between 3 and 6 months after the sclerotherapy procedure, a phone call was made to the patients, and data for the post-procedural questionnaires were collected in the form of a telephone interview. Both questionnaires used in our study were self-constructed. The preoperative survey consisted of three parts. The first one regarded general information about patients, including their age, education, place of living, and a history of chronic diseases and surgeries, including surgeries for endometriosis. In the second part of the survey, there were six questions concerning the symptoms related to endometriosis. In a question regarding main endometriosis-associated symptoms, patients could choose the following statements: “dysmenorrhea”, “hemorrhagic menstruation”, “dyspareunia”, “periovulatory pain”, “infertility”, and “chronic lower abdominal pain”. Further, the patients were asked about the presence and frequency of chronic lower abdominal pain. The respondents endorsed the frequency of this symptom by selecting from among the following statements: “every day”, “several times a week”, “once a week”, “several times a month”, “less frequently than once a month”, or “absence of pain”. The patients were asked under what circumstances the pain most often occurs. We prompt them to choose one or multiple options from the following statements: “during urination”, “during defecation”, “during sexual intercourse”, “perimenstrual”, “periovulatory”, “during physical exertion” and “irrespective of the circumstances”. The severity of pain during menses, sexual intercourse, and pain occurring chronically was evaluated with a Visual Analog Scale (VAS) for pain. The extreme points of this scale were 0 and 10. A higher score represents more pain. The post-sclerotherapy questionnaire consisted of six questions. The patients were asked whether they thought sclerotherapy helped them relieve pain symptoms. Pain during menses, sexual intercourse, and chronic pain were re-evaluated using the same research tool. Further, the patients were asked whether sclerotherapy influenced their quality of life. In addition, information about the use of hormonal therapy after sclerotherapy was collected. The data were collected using MS Excel. Descriptive statistics were presented using mean with standard deviation (SD) and median with interquartile range (IQR) for continuous variables. Categorical data were presented as counts and percentages. The normality of data distribution was assessed using the Shapiro–Wilk test. The statistical significance of differences between the two dependent groups was verified using the Wilcoxon test. The χ2 test with Yates correction was used to evaluate the relationship between nominal variables, while the two-proportion test was used to compare two percentage scores. The results were considered statistically significant at p < 0.05. All analyses were conducted using Statistica 13 software (TIBCO Software Inc., Palo Alto, CA, USA).

Out of the 94 patients who underwent sclerotherapy, agreed to participate in our study, and completed a pre-procedural survey, 35 have been excluded due to the presence of chronic diseases other than endometriosis. Finally, 59 patients were included in the study. Table 1 presents the general characteristics of women participating in this study. The mean age of participants was 33.32 years. The majority of respondents lived in urban areas (69.48%) and had a tertiary education (84.74%). According to the design of our study, none of the participating women had other chronic diseases besides endometriosis. Most of the women had a history of surgeries (67.80%). 42.37% of patients reported that they had undergone surgery for endometriosis. Out of them, 19 (76%) had a single surgery and 6 (24%) received surgical treatment due to endometriosis more than once. In addition, almost 60% of participants had surgery for reasons other than endometriosis. | Table 1. General characteristics of included patients | || | Participants’ characteristics | n | % | | Place of residence | || | A city with more than 500,000 inhabitants | 9 | 15.25 | | A town with 100,000 to 500,000 inhabitants | 21 | 35.60 | | A town with less than 100,000 inhabitants | 11 | 18.64 | | Village | 18 | 30.51 | | Education | || | Secondary | 9 | 15.25 | | Tertiary | 50 | 84.75 | | Chronic diseases | || | Endometriosis | 59 | 100 | | Other diseases | 0 | 0 | | Total surgeries | || | Yes | 40 | 67.80 | | No | 19 | 32.20 | | Endometriosis surgeries | || | One surgery | 19 | 32.20 | | More than one surgery | 6 | 10.17 | | No surgeries | 34 | 57.63 | | Non-endometriosis surgeries | || | Yes | 35 | 59.32 | | No | 24 | 40.68 | The summary of endometriosis-related symptoms, frequency, and circumstances of pain is presented in Table 2. As reported by 76.27% of women, dysmenorrhea was the most often occurring symptom, and, in turn, the least frequently reported one was hemorrhagic menstruation (27.12% of participants). Three women reported an asymptomatic endometriosis course. The largest number of patients (35.59%) admitted that endometriosis-associated pain occurred several times a month. Menstruation (66.10%) and sexual intercourse (30.51%) were the most frequently reported circumstances in which endometriosis-related pain occurred. | Table 2. Characteristics of endometriosis-associated symptoms | || | Characteristics | n | % | | Main endometriosis-related symptoms | || | Dysmenorrhea | 45 | 76.27 | | Hemorrhagic menstruation | 16 | 27.12 | | Dyspareunia | 31 | 52.54 | | Periovulatory pain | 28 | 47.46 | | Infertility | 25 | 42.37 | | Chronic pelvic pain | 32 | 54.24 | | No symptoms | 3 | 5.08 | | Frequency of endometriosis-related pain | || | Every day | 11 | 18.64 | | Several times a week | 18 | 30.51 | | Once a week | 1 | 1.69 | | Several times a month | 21 | 35.59 | | Less frequent than once a month | 5 | 8.47 | | Absence of pain | 3 | 5.08 | | Circumstances of endometriosis-related pain | || | During urination | 5 | 8.47 | | During defecation | 8 | 13.56 | | During sexual intercourse | 18 | 30.51 | | Perimenstrual | 39 | 66.10 | | Periovulatory | 8 | 13.56 | | During physical exertion | 4 | 6.78 | | Irrespective of the circumstances | 8 | 13.56 | | Absence of pain | 3 | 5.08 | The procedure was completed successfully in all patients. All patients had a single cyst of one ovary. No complications of sclerotherapy have been noticed in any patient. The results of histopathological examinations revealed the presence of endometrial cysts in all cases. 74.58% of respondents did not use hormonal treatment in the post-sclerotherapy period. The percentage of women in whom sclerotherapy significantly reduced pain was significantly higher than the percentage of women in whom sclerotherapy did not exert such an effect (p = 0.014) (Tab. 3). The differences between mean VAS scores measured for menstruation, sexual intercourse, and chronic pelvic pain, before and after sclerotherapy, were statistically significant (Fig. 1). Significantly more women stated that sclerotherapy substantially improved their quality of life in comparison to women who reported that did not observe such an improvement (p = 0.006) (Tab. 4). More than 88% of patients stated that they would recommend sclerotherapy to other patients and that was not related to the history of endometriosis surgeries (Tab. 5). | Table 3. Has sclerotherapy helped to reduce pain? | || | Answers | n | % | | Significantly reduced pain | 40 | 67.80 | | Slightly reduced pain | 6 | 10.17 | | No change | 8 | 13.56 | | Aggravated pain | 1 | 1.69 | | No pain before sclerotherapy | 4 | 6.78 | | Table 4. Has sclerotherapy influenced your quality of life? | || | Answers | n | % | | Significantly improved quality of life | 44 | 74.58 | | Slightly improved quality of life | 2 | 3.39 | | No change in quality of life | 12 | 20.34 | | Impaired quality of life | 1 | 1.69 | | Table 5. Would you recommend sclerotherapy to other patients? | || | Answers | n | % | | Yes | 52 | 88.14 | | No | 5 | 8.47 | | I don’t know | 2 | 3.39 | No correlation between significant pain alleviation and a history of endometriosis surgery was found. Pain alleviation was not related to the cysts’ volumes resolved with sclerotherapy. Regardless of the time of the second interview, the percentage of women reporting significant pain alleviation was similar. Importantly, the usage of hormonal treatment in the post-sclerotherapy period also did not affect pain relief (Tab. 6). | Table 6. Evaluation of associations between significant pain reduction and selected parameters, including the history of endometriosis surgeries, cyst volume, post-sclerotherapy hormonal treatment, and time of second interview | ||| | Parameters | Significant pain reduction n (%) | Non-significant pain reduction n (%) | p value | | Endometriosis surgery | 0.25 | || | Yes | 19 (32.20%) | 6 (10.17%) | | | No | 21 (35.59%) | 13 (22.03%) | | | The volume of the cyst | 0.45 | || | ≤ 20 mL | 17 (28.81%) | 10 (16.95%) | | | 21–40 mL | 15 (25.42%) | 4 (6.78%) | | | > 40 mL | 8 (13.56%) | 5 (8.47%) | | | Hormonal treatment | 0.07 | || | Yes | 13 (22.03%) | 2 (3.39%) | | | No | 27 (45.76%) | 17 (28.81%) | | | Time | 0.70 | || | 3 months | 6 (10.17%%) | 0 (0%) | | | 4–5 months | 31 (52.54%) | 17 (28.81%) | | | 6 months | 3 (5.08%) | 2 (3.39%) |

Treatment of endometrial cysts is a complex process that depends on the pivotal patient’s symptoms [17]. Main approaches, including surgery or pharmacotherapy, have some limitations. Laparoscopic cystectomy of endometrial cysts results in decreased ovarian reserve and does not improve assisted reproductive technologies (ART) outcomes [18, 19]. Also, despite the high efficacy of pharmacotherapy in pain alleviation, this method does not lead to the disappearance of endometrial cysts and cannot be offered to patients trying to conceive [20]. Hence, alternative, less invasive methods of resolving endometrial cysts, such as sclerotherapy, are becoming increasingly important [16]. Our results demonstrate that a very large number of patients experienced pain relief after sclerotherapy. This was both a general observation of the patients and an observation related to different types of pain, including pain during menstruation, pain during intercourse, and chronic pain in the lower abdomen. We found that a total of 77.97% of patients perceived significant or subtle pain alleviation, with 67.8% of them reporting a significant improvement. The effects of sclerotherapy on endometriosis-related pain symptoms have been the topic hitherto several times addressed in the literature. Nevertheless, the obtained results are quite divergent. While Koo et al. [21] and Garcia-Tejedor et al. [22] reported pain relief in 95% and 96% of patients, respectively, Vaduva et al. [23] revealed a reduction in symptoms in 48.1% of affected women. The least encouraging results were presented by Noma et al. [24], who showed that only 27% of patients had an overall improvement in their symptoms. Our results remain most consistent with those presented by Ikuta et al. [25] and Garcia-Tejedor et al. [26], who observed improvement in 83.3% and 82.4% of patients, respectively. The reasons for such inconsistencies may be ascribed to the methodology of the presented studies, including different techniques of ethanol administration, different follow-up times, and the presence or absence of post-sclerotherapy pharmacotherapy. Unsurprisingly, in our study, the most often reported endometriosis-related symptoms were dysmenorrhea, dyspareunia, and chronic pelvic pain. Considering that the current literature complies with such a tendency [27], before the onset of the study, we decided to evaluate these three types of pain separately, using the VAS scale before and after sclerotherapy. In all three cases, significant pain relief was noted. Previously conducted studies also used this scale as a research tool, however, most researchers asked participants about general pain sensations, without distinguishing pain circumstances [21, 28, 29]. Only Anvari et al. [30] used VAS scores for the assessment of dyspareunia and dysmenorrhea separately and consistently with our study have noticed symptoms’ mitigation. Our results indicated the lack of difference in pain relief between patients for whom sclerotherapy was the first non-pharmacological treatment and those who had a history of surgery for endometriosis. Similarly, in the study conducted by the research team of Lee et al. [31], changes in VAS score for pain did not vary substantially between the group with sclerotherapy as primary treatment and the group with prior surgical treatment. Another noticeable finding from our study is the fact that pain alleviation was not related to the administration of post-procedural hormonal treatment. This is an unexpected observation, especially in light of the reports, which revealed that hormonal treatment in the post-surgical period contributed to pain relief [32]. We also found that pain relief was unrelated to the time of the second interview. These observations are highly encouraging; however, future studies should have a longer follow-up time. To the best of our knowledge, this is the first study to focus on the impact of sclerotherapy on the quality of life. In this regard, our results are highly satisfactory, as we showed that almost 75% of patients observed substantial improvement in life quality. Although the precise definition of all components characterizing this concept is hard to establish, it can be summarized that “quality of life” involves a wide range of domains concerning psychological state and patients’ social functioning [33]. Many patients had a positive attitude towards the course of the sclerotherapy procedure, which expressed their willingness to recommend the procedure to other women. In our center, the treatment was carried out as part of a one-day stay, therefore, we hypothesized that this would be a reason for such a positive assessment. The literature has also pointed out that sclerotherapy had a shorter hospital stay compared to laparoscopy [23]. Therefore, we expected that patients who had previously undergone surgery for endometriosis would be more likely to recommend this procedure compared to those who had not undergone surgical treatment for endometriosis, however, there was no such correlation in our study. A noticeable advantage of our study was its design, assuming the exclusion of patients suffering from chronic diseases. Chronic diseases can substantially impair life quality; hence, we want to eliminate the risk of such affecting patients’ well-being [34]. Nevertheless, our study is not free from some limitations. First, our study group was relatively small. Additionally, the second questionnaires were collected via telephone interviews, as some of the patients, due to the remote place of residence, made follow-up visits outside our center. Further exploration of the topic, including the correlation of changes in pain and psychological aspects with more clinical data, e.g., recurrence or AMH values, is required. We believe that future scientific efforts should be focused on the evaluation of sclerotherapy outcomes on other psychological parameters and procreation plans of the patients.

Sclerotherapy for patients with ovarian endometriosis alleviates pain across menstruation, intercourse, and chronic pain domains. Pain relief was observed regardless of primary cyst volume, post-procedural pharmacotherapy, and the time that had elapsed since sclerotherapy. Treatment with the use of sclerotherapy can also improve the quality of life. Patients declare high satisfaction with sclerotherapy, which manifests itself in their willingness to recommend this procedure to other patients. Article information and declarations Data availability statement The data that support the findings of the study are available on request from the corresponding author, KF. Ethics statement The study was conducted in accordance with the Declaration of Helsinki, and approved by the Medical University of Lublin Ethics Committee (KE-0254/30/01/2024). Informed consent was obtained from all subjects involved in the study. Author contributions IDD — 25% — concept; article draft. KF — 25% — concept; corresponding author. MA — 20% — analysis. MC — 10% — analysis. BT — 10% — interpretation of data. GP — 10% — concept. Funding This work was supported by a grant from the Medical University of Lublin (grant no. DS121).

None. Conflict of interest The authors declared that they have no potential conflicts of interest. Supplementary material None.