Levonorgestrel-releasing intrauterine device treatment in heavy menstrual bleeding: Correlation with endometrial pathology and quality of life.

Heavy menstrual bleeding is a common issue that can significantly affect the lives of women of reproductive age and defined as losing more than 80 ml of menstrual blood per cycle [ 1 ]. The prevalence of heavy menstrual bleeding in reproductive-age women, based on objective measurements, ranges from 9% to 14%, but studies that rely on subjective assessments have reported rates as high as 20% to 52% [ 2 , 3 ]. Since heavy menstrual bleeding is a subjective evaluation, it has been stated in various international guidelines that the diagnosis should not be based solely on objective measurements, and that it would be more accurate to evaluate it as excessive menstrual blood loss that affects women’s physical, emotional, social and material quality of life [ 4 – 6 ]. To diagnose underlying causes, imaging techniques such as pelvic or transvaginal ultrasound and hysteroscopy are utilized, along with tissue sampling. Endometrial biopsy has high sensitivity for detecting benign, premalignant and malignant intrauterine pathologies [ 7 , 8 ]. In patients with heavy menstrual bleeding, the most common endometrial sampling results reveal a normal cyclic endometrium (proliferative, secretory and shedding phases) (28.6–56.8%), while the most frequently observed pathology, regardless of age group, is hormonal imbalance patterns (7.5–19.5%). Within the hormonal imbalance pattern, conditions such as irregular proliferative endometrium (7.5–19.5%), stromal and glandular destructive non-secretory endometrium, luteal phase defect, and medication effects can be identified. Irregular proliferative endometrium represents an exaggerated proliferative phase indicative of chronic anovulation, especially during the perimenopausal years. Other causes include pregnancy complications, endometrial polyps, endometrial hyperplasia, carcinomas, and chronic endometritis [ 9 – 11 ]. Heavy menstrual bleeding can be treated using medical or surgical methods, depending on its etiology [ 12 ]. Medical treatment including hormonal drugs and other pharmacological approaches is widely used. One such option is the 52 mg Levonorgestrel-releasing intrauterine device (LNG-IUD), which is recommended as the best first-line treatment for patients with heavy menstrual bleeding who have no additional pathologies or have fibroids smaller than 3 centimeters or adenomyosis [ 13 ]. Various studies have demonstrated the efficacy of the LNG-IUD compared to other systemic medications and surgical options, showing that it not only effectively manages symptoms but also contributes to better quality of life [ 14 , 15 ]. There are studies in the literature evaluating the efficacy of the LNG-IUS according to the underlying medical pathology. Several studies have investigated the effectiveness of the LNG-IUS in different types and severities of adenomyosis, reporting variable results [ 16 , 17 ]. Similarly, in women with uterine fibroids, the LNG-IUS has been shown to be effective in reducing heavy menstrual bleeding, although higher expulsion rates have been reported [ 18 ]. In addition, the LNG-IUS has been found to thin the endometrium and to be highly effective in cases of localized endometrial pathology [ 19 ]. However, no study has been found comparing the effects of benign endometrial pathology results on the quality of life after LNG-IUS treatment. Therefore, the aim of the present study was to evaluate whether endometrial sampling results have an impact on the treatment outcomes and quality of life in patients with heavy menstrual bleeding using the LNG-IUS.

The demographic data of the 143 patients included in the study are presented in Table 1 . Histopathological examination showed a variety of patterns consisting of normal cyclical patterns showing proliferative, secretory, and shedding phases in 93 of the 143 total cases. ( Table 1 ). † LNG-IUD: The Levonorgestrel Releasing Intrauterine Device ‡Hg: Hemoglobin n: Total Number of Cases. After the application of the LNG-IUD, all parameters of the SF-36 quality of life scale and the total MMAS score showed a significant increase compared to before the LNG-IUD insertion (p < 0.05) ( Table 2 ). Additionally, the Beck Depression Inventory score and depression rate significantly decreased after the LNG-IUD application compared to before (p < 0.05) ( Table 2 ) Md: Median w Wilcoxon test N MC Nemar test †: LNG-IUD: The Levonorgestrel Releasing Intrauterine Device ‡: MMAS: Menorrhagia Multi-Attribute Scale §: SF-36: 36-Item Short Form Health Survey. In the group with a normal cyclic pattern from endometrial sampling, the patients’ age was significantly lower than that of the group with a hormonal imbalance pattern (p < 0.05) ( Table 3 ). Md: Median m Mann-whitney u test X² Ki-kare test (Fischer test) †: LNG-IUD: The Levonorgestrel Releasing Intrauterine Device ‡: Hg: Hemoglobin. There were no significant differences between the groups with normal cyclic pattern and hormonal imbalance pattern regarding gravida, parity, the rate of having any additional diseases, hypothyroidism, hypertension, other comorbidities, and hemoglobin levels before LNG-IUD insertion (p > 0.05) ( Table 3 ). There were no significant differences between the groups with normal cyclic pattern and hormonal imbalance pattern regarding bleeding pattern after LNG-IUD insertion, the rate of LNG-IUD removal, and the rate of hysterectomy (p > 0.05) ( Table 3 ). Additionally, the depression rate and Beck Depression Inventory scores did not show significant differences between the groups (p > 0.05) ( Table 3 ). When comparing the groups with normal cyclic pattern and hormonal imbalance pattern based on endometrial pathology, there were no significant differences in all parameters of the SF-36 questionnaire and the total MMAS score before and after LNG-IUD insertion (p > 0.05) ( Table 4 ). Md: Median †: SF-36: 36-Item Short Form Health Survey ‡:LNG-IUD: The Levonorgestrel Releasing Intrauterine Device §:MMAS: Menorrhagia Multi-Attribute Scale.

This study makes a significant contribution to the literature as the first to comprehensively evaluate the impact of LNG-IUD on quality of life according to endometrial pathology results. It not only fills a critical gap in existing research but also provides valuable guidance for clinicians in selecting the most suitable patients for LNG-IUD treatment.

The study is a retrospective cohort study conducted at the Training and Research Hospital. All patients who underwent a 52 mg LNG-IUD (Mirena® Bayer, Whippany, N J 07981, Leverkusen, Germania) insertion between January 1, 2023, and January 30, 2024 were screened from the hospital system, and a total of 456 patients were identified. Of these patients, 244 were excluded from the study because endometrial pathology sampling was not performed or because LNG-IUD insertion was performed for contraceptive purposes. Of the 212 patients who underwent endometrial sampling, 66 were excluded because their phone numbers were unavailable or they refused to participate in the study. 1 patient with hyperplasia with atypia and 2 patients with simple hyperplasia without atypia were excluded. A total of 143 patients aged 28–54 years who underwent endometrial sampling due to heavy menstrual bleeding and subsequently underwent LNG-IUD insertion were included in the study ( Fig 1 ). Medical records of the participants were reviewed between 26.07.2024 and 10.12.2024. Patient demographic data was extracted from hospital records. They were then contacted by phone and given a retrospective questionnaire about their clinical status before and six months after LNG-IUD placement. The results were documented in writing on the questionnaire forms. Menstrual pattern 6 months after LNG-IUD insertion was noted according to The International Federation of Obstetrics and Gynecology (FIGO) current classification of abnormal uterine bleeding [ 20 ]. All endometrial sampling was performed before The LNG-IUD insertion due to heavy menstrual bleeding. The LNG-IUD was inserted at any time when the researcher is reasonably certain that the participant is not pregnant. After the device was inserted, transvaginal ultrasound was used to confirm correct placement. Additionally, blood hemoglobin and hematocrit levels were evaluated on the same day. Those who declined to participate or did not give consent to join the study were excluded ( Fig 1 ). Anticoagulant users, individuals with hereditary coagulation disorders, those with uterine fibroids larger than 3 cm, patients who did not undergo endometrial sampling, patients without heavy menstrual bleeding who received an LNG-IUD for contraception, and those with bleeding due to cervical or vaginal etiologies were excluded from the study. Also 3 patients who underwent LNG-IUD but had endometrial pathologies such as atypical (1 case) or simple endometrial hyperplasia (2 cases) were excluded from the study. Endometrial pathology results of patients with LNG-IUD insertion were obtained from the hospital’s electronic system. The most common endouterine sampling results for heavy menstrual bleeding were normal cycle patterns (26.7%) and hormonal imbalance patterns (30.5%). The next most common endometrial pathology result was endometrial polyps (24.3%) [ 21 ]. In our study, patients were divided into two groups as normal cycle patterns and hormonal imbalance patterns to evaluate the outcome of LNG-IUD treatment. Because endometrial polyps are treated surgically, LNG-IUDs are not included in the study because they are not administered. Patients whose endometrial pathology revealed proliferative, secretory, and shedding phases were included in the normal cycle pattern group. Patients whose endometrial pathology revealed irregular proliferative endometrium, hormonal effects, or anovulatory endometrium were included in the hormonal imbalance pattern group. In this study, three assessment tools were utilized: MMAS questionnaire, the Medical Outcomes Study 36-Item Short Form Health Survey (MOS SF-36), and the Beck Depression Inventory. In 1998, Shaw and colleagues designed the Menorrhagia Multiattribute Scale (MMAS), which is widely used today for the subjective assessment of menorrhagia-related quality of life. The MMAS has demonstrated high construct validity and reliability, demonstrating strong internal consistency and retest reliability, and it also measures treatment outcomes. The MMAS questionnaire assesses the impact of abnormal uterine bleeding on six different domains of life, including practical difficulties, social life, psychological health, physical health and well-being, daily routines, and family relationships [ 22 , 23 ]. The MMAS questionnaire was translated into the local language by the researchers conducting this study and administered to patients during telephone interviews, with responses recorded by the gynecologists. The SF-36 questionnaire, a reliable and well-validated tool for assessing overall well-being, consists of 36 items that measure 8 scales: vitality, physical functioning, bodily pain, general health perception, physical role functioning, emotional role functioning, social role functioning, and mental health [ 24 ]. The Beck Depression Inventory is a 21-item scale used to assess a patient’s psychological health. Each question has four response options. The total score from the patient’s responses is categorized as follows: 0–9 indicates normal, 10–18 indicates mild depression, 19–29 indicates moderate depression, and 30–63 indicates severe depression. The study was conducted in accordance with the Declaration of Helsinki. Approval was received from the Ethics Committee with decision number 368 dated December 22, 2023. Statistical analysis: Descriptive statistics for the data included mean, standard deviation, median, minimum, maximum, frequency, and percentage values. The Kolmogorov–Smirnov and Shapiro–Wilk tests were applied to continuous variables to assess whether they followed a normal distribution before selecting appropriate parametric or non-parametric statistical tests. For normally distributed quantitative independent data, the independent samples t-test was used, while the Mann-Whitney U test was employed for non-normally distributed quantitative independent data. The Wilcoxon test was applied for dependent quantitative data, and the chi-square test was used for qualitative independent data. Analyses were conducted using SPSS version 28.0.

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