Comparative efficacy of dienogest versus levonorgestrel-releasing intrauterine system in the symptom control of adenomyosis: A randomized controlled trial

Background: Adenomyosis is a common benign uterine disorder associated with dysmenorrhea, chronic pelvic pain, and heavy menstrual bleeding, often requiring long -term conservative treatment. Among medical options, dienogest and the levonorgestrel -releasing intrauterine system (LNG -IUS) are widely used, but comparative evidence regarding their relative efficacy in symptom control remains limited.

To evaluate and compare the efficacy of dienogest and LNG -IUS in the symptom control of adenomyosis, with particular reference to pain relief, menstrual blood loss, ultrasonographic changes, and adverse effects.

This randomized controlled trial included 100 women with symptomatic adenomyosis, allocated equally to a dienogest group (2 mg orally once daily) or an LNG -IUS group. Participants were followed at 3, 6, and 12 months. Pain symptoms were assessed using visual analog scale (VAS) scores for dysmenorrhea and chronic pelvic pain, while menstrual blood loss was evaluated using pictorial blood loss assessment chart (PBAC) scores. Ultrasonographic parameters included uterine volume and junctional zone thickness. Adverse effects and treatment continuation were also recorded. Follow -up outcome analyses were performed on a per-protocol basis.

Both treatment groups showed significant improvement in dysmenorrhea, chronic pelvic pain, and menstrual blood loss over 12 months. Dienogest produced greater reduction in dysmenorrhea than LNG - IUS (between -group change p=0.010), whereas improvement in chronic pelvic pain was comparable between groups (p=0.458). LNG -IUS was superior in reducing menstrual blood loss, with significantly lower PBAC scores at 3, 6, and 12 months, and a higher proportion of marked menstrual blood loss response at 12 months (82.0% vs 48.0%, p=0.002). Both groups demonstrated significant ultrasonographic improvement; reduction in junctional zone thickness favored LNG -IUS (between-group change p=0.002), while reduction in uterine volume was comparable. Treatment discontinuation/removal was significantly more frequent in the LNG-IUS group than in the dienogest group (32.0% vs 4.0%, p<0.001).

Both dienogest and LNG-IUS were effective in the conservative management of symptomatic adenomyosis. Dienogest provided better pain relief, particularly for dysmenorrhea, whereas LNG -IUS was more effective in reducing menstrual blood loss and improving junctional zone thickness. Treatment choice should therefore be individualized according to the predominant symptom profile and tolerability.

Adenomyosis, dienogest, levonorgestrel -releasing intrauterine system, dysmenorrhea, menstrual blood loss

Adenomyosis is a common benign uterine disorder characterized by the presence of endometrial glands and stroma within the myometrium, along with surrounding smooth muscle hyperplasia and hypertrophy. It is now understood as a complex condition rather than a simple histopathological finding. Its pathogenesis appears multifactorial, involving tissue injury and repair, hormonal influences, inflammation, fibrosis, and abnormal uterine peristalsis [1]. These mechanisms help explain why adenomyosis can produce persistent symptoms and why its clinical behavior varies from one woman to another. The condition is increasingly recognized in women of reproductive age and is frequently associated with dysmenorrhea, heavy menstrual bleeding, chronic pelvic pain, and infertility. Clinical presentation is often variable, and diagnosis may be delayed because symptoms overlap with other gynecological disorders such as fibroids and endometriosis [2]. Improved imaging, especially transvaginal ultrasonography and magnetic resonance imaging, has made noninvasive diagnosis more practical, but adenomyosis still remains underdiagnosed in many settings [2]. International Journal of Clinical Obstetrics and Gynaecology https://www.gynaecologyjournal.com ~ 895 ~ The burden of disease is considerable because symptoms may be prolonged, recurrent, and severe enough to interfere with daily activity and quality of life. Management of adenomyosis remains challenging. Treatment depends on symptom severity, age, reproductive plans, extent of disease, and patient preference. Historically, hysterectomy was considered the definitive treatment, particularly in women with severe symptoms who had completed childbearing [3]. Many patients, however, seek uterus -preserving options. This has increased the importance of conservative treatment strategies, especially medical therapy, for controlling pain and abnormal uterine bleeding [3, 7]. Among available medical options, progestin -based therapies have gained particular importance. Dienogest is widely used because of its anti -inflammatory, anti -proliferative, and progesterone-mediated effects on ectopic endometrial tissue. It has shown benefit in reducing pain symptoms in women with adenomyosis and is increasingly used as a long -term medical treatment option [4, 7]. The levonorgestrel -releasing intrauterine system (LNG-IUS) is another important conservative treatment. It acts locally on the endometrium and has been reported to be highly effective in reducing menstrual blood loss and dysmenorrhea in women with adenomyosis [5, 8]. In long -term follow-up studies, LNG -IUS has shown sustained symptom relief, although side effects such as irregular bleeding and device expulsion may occur [7]. There is growing interest in comparing these two treatment modalities because they differ in route of administration, mechanism of action, side -effect profile, and patient acceptability. A recent systematic review and meta -analysis comparing LNG -IUS and dienogest suggested that both are effective in the management of adenomyosis, but differences may exist in the degree of symptom control and adverse effects [4]. This comparison is clinically important because adenomyosis often requires long -term treatment, and the choice of therapy must balance efficacy, tolerability, compliance, and impact on quality of life. Despite expanding evidence, there is still no universal consensus on the optimal conservative treatment for adenomyosis. The condition itself is heterogeneous, and treatment response may differ according to symptom pattern, disease extent, and patient characteristics [1 ,2, 7]. In addition, adenomyosis remains an important cause of abnormal uterine bleeding and pelvic pain among women undergoing gynecologic evaluation, underlining the need for practical and effective symptom -control strategies [6]. The present study was undertaken to evaluate and compare the efficacy of dienogest and LNG -IUS in the symptom control of adenomyosis. The study specifically aimed to compare improvement in pain symptoms and menstrual blood loss, assess ultrasonographic changes after treatment, and evaluate the adverse effects associated with both treatment modalities Aim To evaluate and compare the efficacy of dienogest and LNG - IUS in the symptom control of adenomyosis.

1. To compare improvement in pain symptoms and menstrual blood loss between the two treatment groups. 2. To compare ultrasonographic changes after treatment between the two groups. 3. To assess and compare the adverse effects associated with both treatment modalities.

Study design This study was a randomized controlled trial conducted to compare the efficacy of dienogest and levonorgestrel -releasing intrauterine system (LNG -IUS) in the symptom control of adenomyosis. Place of study The study was carried out in the Department of Obstetrics and Gynaecology Barasat govt medical college. North 24 pgs Kolkata west Bengal Study duration The duration of the study was 1 year. Sample size A total of 100 patients were included in the study. Study population Women diagnosed with symptomatic adenomyosis attending the gynecology outpatient department and fulfilling the eligibility criteria were enrolled in the study. Inclusion criteria Patients were included if they: • had adenomyosis diagnosed on clinical and ultrasonographic assessment • had symptoms such as dysmenorrhea, chronic pelvic pain, and/or heavy menstrual bleeding attributable to adenomyosis • were willing to undergo treatment with either dienogest or LNG-IUS • were willing for regular follow-up • gave informed consent to participate in the study Exclusion criteria Patients were excluded if they: • were pregnant or suspected to be pregnant • had coexisting large fibroids or other significant pelvic pathology that could independently affect symptoms • had suspected or confirmed genital tract malignancy • had active pelvic inflammatory disease or genital tract infection • had uterine cavity distortion or any contraindication to LNG-IUS insertion • had contraindications to progestin therapy • had severe systemic illness precluding participation • were unwilling for follow -up or had incomplete baseline data Randomization and grouping After enrollment, the patients were randomized into two groups of 50 each: • Group A: Dienogest group • Group B: LNG-IUS group

of study A detailed history was taken from all patients, including age, parity, duration of symptoms, menstrual complaints, and pain symptoms. Baseline clinical examination and ultrasonographic assessment were carried out before treatment. Patients in Group A received dienogest 2 mg orally once daily. Patients in Group B underwent insertion of a levonorgestrel - International Journal of Clinical Obstetrics and Gynaecology https://www.gynaecologyjournal.com ~ 896 ~ releasing intrauterine system (LNG -IUS) under standard aseptic precautions. Parameters assessed 1. Pain symptoms Pain was assessed using a visual analog scale (VAS). The major pain symptoms evaluated included: • dysmenorrhea • chronic pelvic pain Scores were recorded at baseline and during follow-up visits. Menstrual blood loss Menstrual blood loss was assessed using a pictorial blood loss assessment chart (PBAC) score. This was used to compare improvement in bleeding symptoms between the two treatment groups. Ultrasonographic parameters Ultrasonographic evaluation was done at baseline and during follow-up. The parameters assessed included: • uterine volume • maximum myometrial thickness • junctional zone thickness These parameters were used to assess structural changes following treatment. Adverse effects The adverse effects associated with both treatment modalities were documented during follow-up. These included: • irregular bleeding or spotting • amenorrhea • weight gain • breast tenderness • mood changes • gastrointestinal symptoms • device expulsion • discontinuation or removal of treatment Follow-up All patients were followed up at 3 months, 6 months, and 12 months after initiation of treatment. At each visit, pain symptoms, menstrual blood loss, adverse effects, and treatment continuation were assessed. Ultrasonographic reassessment was also performed during follow-up. Outcome measures The primary outcome measures were: 1. improvement in pain symptoms 2. reduction in menstrual blood loss The secondary outcome measures were: 1. ultrasonographic changes after treatment 2. adverse effects associated with both treatment modalities 3. overall treatment response at 12 months Statistical analysis Data were entered into Microsoft Excel and analyzed using appropriate statistical software. Quantitative variables were expressed as mean ± standard deviation, and qualitative variables were presented as frequency and percentage. Comparison between the two groups for continuous variables was performed using the independent t -test. Categorical variables were compared using the chi -square test or Fisher’s exact test, as appropriate. Changes over follow-up were analyzed using repeated-measures analysis. A p value less than 0.05 was considered statistically significant. A per -protocol analysis was performed. Only participants who remained on the assigned treatment and had evaluable outcome data at the relevant follow-up visit were included in the analysis. Participants who discontinued treatment, had device removal/expulsion, or were lost to follow -up were excluded from analysis after the point of discontinuation. Therefore, the number analyzed at each follow -up time point could differ from the number randomized. Ethical considerations The study was conducted after obtaining approval from the Institutional Ethics Committee. Written informed consent was obtained from all participants before enrollment. Confidentiality of patient information was maintained throughout the study. Data collection procedure Eligible patients were enrolled after clinical and ultrasonographic diagnosis of adenomyosis. Baseline demographic, clinical, and ultrasonographic details were recorded in a predesigned case record proforma. Patients were then randomized into the dienogest and LNG -IUS groups. Follow-up assessments were carried out at 3, 6, and 12 months to record pain scores, menstrual blood loss, ultrasonographic changes, adverse effects, and treatment continuation.

A total of 100 women with adenomyosis were randomized equally to the dienogest group (n=50) or the levonorgestrel - releasing intrauterine system (LNG-IUS) group (n=50). Baseline characteristics are presented for all randomized participants. Follow-up outcome analyses were performed on a per -protocol basis and therefore included only those participants who continued the assigned treatment and had evaluable data at the relevant visit. During follow -up, treatment discontinuation/removal occurred in 2 participants in the dienogest group and 16 participants in the LNG -IUS group.

are presented according to baseline comparability, symptomatic outcomes, ultrasonographic changes, and treatment-related adverse effects. Baseline characteristics The two randomized groups were comparable at baseline with respect to age, body mass index, parity, symptom duration, uterine size, hemoglobin level, pain severity, menstrual blood loss, and baseline ultrasonographic parameters. No statistically significant intergroup differences were observed for baseline variables, indicating adequate baseline balance between the trial arms (Table 1). International Journal of Clinical Obstetrics and Gynaecology https://www.gynaecologyjournal.com ~ 897 ~ Table 1: Baseline characteristics of the study groups Variable Dienogest (n=50) LNG-IUS (n=50) p value Age (years) 37.36 ± 5.66 38.36 ± 5.04 0.353 BMI (kg/m²) 23.96 ± 3.20 24.80 ± 3.93 0.245 Parity 1.32 ± 1.02 1.70 ± 1.13 0.080 Symptom duration (months) 17.36 ± 7.29 18.12 ± 7.08 0.598 Uterine size (weeks) 9.88 ± 1.81 9.76 ± 1.96 0.752 Hemoglobin (g/dL) 10.19 ± 1.15 10.37 ± 1.11 0.427 Baseline dysmenorrhea VAS 7.08 ± 1.55 7.20 ± 1.55 0.700 Baseline chronic pelvic pain VAS 5.78 ± 1.82 6.32 ± 1.35 0.095 Baseline PBAC score 251.90 ± 63.78 229.18 ± 62.27 0.075 Baseline uterine volume (mL) 184.10 ± 52.25 192.58 ± 51.82 0.417 Baseline JZ thickness (mm) 15.28 ± 2.71 15.04 ± 2.41 0.644 Adenomyosis type: Diffuse 36 (72.0%) 37 (74.0%) 1.000 Adenomyosis type: Focal 14 (28.0%) 13 (26.0%) 1.000 Pain outcomes Both treatment groups demonstrated progressive reduction in pain scores during follow -up. Dysmenorrhea and chronic pelvic pain improved significantly within each group across serial visits (both within -group p<0.001). Between -group comparison showed a greater 12 -month reduction in dysmenorrhea visual analogue scale (VAS) score in the dienogest group than in the LNG-IUS group (between -group change p=0.010), whereas reduction in chronic pelvic pain was similar between groups (p=0.458) (Table 2 and Table 2b). Figure 1 illustrates the decline in mean dysmenorrhea VAS over time in both treatment arms. Table 2: Comparison of pain outcomes between groups over follow-up Values are mean ± SD. Between-group p values compare Dienogest versus LNG-IUS at each time point. Outcome Time point Dienogest (n=50) LNG-IUS (n=50) Between-group p value Dysmenorrhea VAS Baseline 7.08 ± 1.55 7.20 ± 1.55 0.700 Dysmenorrhea VAS 3 months 5.16 ± 1.57 5.56 ± 1.66 0.218 Dysmenorrhea VAS 6 months 3.64 ± 1.68 4.32 ± 1.82 0.055 Dysmenorrhea VAS 12 months 2.54 ± 1.68 3.20 ± 1.84 0.064 Chronic pelvic pain VAS Baseline 5.78 ± 1.82 6.32 ± 1.35 0.095 Chronic pelvic pain VAS 3 months 4.50 ± 1.73 5.04 ± 1.44 0.093 Chronic pelvic pain VAS 6 months 3.66 ± 1.81 4.16 ± 1.52 0.138 Chronic pelvic pain VAS 12 months 2.62 ± 2.00 3.32 ± 1.67 0.061 Note: Follow-up outcomes were analyzed on a per-protocol basis; denominators at each time point reflect participants who remained on assigned treatment and had evaluable data. Additional statistics for pain outcomes Within-group p values are from repeated -measures ANOVA across all visits; change p compares baseline -to-12-month improvement between groups. Outcome Within-group p (Dienogest) Within-group p (LNG-IUS) Between-group p for 12-month change Dysmenorrhea VAS <0.001 <0.001 0.010 Chronic pelvic pain VAS <0.001 <0.001 0.458 Fig 1 Trend in mean dysmenorrhea VAS score during follow-up in the dienogest and LNG-IUS groups. International Journal of Clinical Obstetrics and Gynaecology https://www.gynaecologyjournal.com ~ 898 ~ Menstrual blood loss outcomes Menstrual blood loss, assessed by pictorial blood loss assessment chart (PBAC) score, decreased significantly over time in both groups (within -group p<0.001 for each). However, the LNG -IUS group showed significantly greater improvement than the dienogest group from as early as 3 months, and this advantage widened by 6 and 12 months. At 12 months, the between-group difference in PBAC score was highly significant (p<0.001), and the change from baseline also favored LNG -IUS (p=0.001). Marked menstrual blood loss response at 12 months was more frequent with LNG -IUS than with dienogest (82.0% vs 48.0%, p=0.002) (Table 3, Table 3b, and Table 3c). Figure 2 depicts the trend in mean PBAC score over follow -up in both groups. Table 3: Comparison of menstrual blood loss outcomes between groups over follow-up Outcome Time point Dienogest (n=50) LNG-IUS (n=50) Between-group p value PBAC score Baseline 251.90 ± 63.78 229.18 ± 62.27 0.075 PBAC score 3 months 205.70 ± 64.45 171.40 ± 58.10 0.006 PBAC score 6 months 166.86 ± 66.96 122.70 ± 56.56 <0.001 PBAC score 12 months 128.86 ± 71.39 75.32 ± 64.02 <0.001 Table 3b: Menstrual blood loss response at 12 months Outcome Dienogest (n=50) LNG-IUS (n=50) Between-group p value MBL response at 12 months: Marked 24 (48.0%) 41 (82.0%) 0.002 MBL response at 12 months: Moderate 22 (44.0%) 7 (14.0%) MBL response at 12 months: Minimal 4 (8.0%) 2 (4.0%) Additional statistics for menstrual blood loss outcomes Outcome Within-group p (Dienogest) Within-group p (LNG-IUS) Between-group p for 12-month change PBAC score <0.001 <0.001 0.001 Menstrual blood loss response at 12 months 0.002 Fig 2: Trend in mean PBAC score during follow-up in the dienogest and LNG-IUS groups. Ultrasonographic outcomes Ultrasonographic follow -up showed significant reduction in uterine volume and junctional zone thickness in both groups over time (all within -group p<0.001). The reduction in uterine volume numerically favored LNG -IUS but did not reach statistical significance at 12 months (between -group change p=0.063). In contrast, reduction in junctional zone thickness was significantly greater in the LNG -IUS group at 12 months (between-group change p=0.002), indicating superior ultrasonographic regression of adenomyotic changes with LNG - IUS for this parameter (Table 4 and Table 4b). Table 4: Comparison of ultrasonographic outcomes between groups Outcome Time point Dienogest (n=50) LNG-IUS (n=50) Between-group p value Uterine volume (mL) Baseline 184.10 ± 52.25 192.58 ± 51.82 0.417 Uterine volume (mL) 6 months 166.30 ± 52.43 170.66 ± 51.19 0.675 Uterine volume (mL) 12 months 152.14 ± 53.43 154.08 ± 52.42 0.855 Junctional zone thickness (mm) Baseline 15.28 ± 2.71 15.04 ± 2.41 0.644 Junctional zone thickness (mm) 6 months 13.94 ± 2.80 13.27 ± 2.36 0.193 Junctional zone thickness (mm) 12 months 12.83 ± 2.85 11.95 ± 2.38 0.099 International Journal of Clinical Obstetrics and Gynaecology https://www.gynaecologyjournal.com ~ 899 ~ Additional statistics for ultrasonographic outcomes Outcome Within-group p (Dienogest) Within-group p (LNG-IUS) Between-group p for 12-month change Uterine volume <0.001 <0.001 0.063 Junctional zone thickness <0.001 <0.001 0.002 Adverse effects and treatment tolerability The overall adverse -effect profile differed between the two modalities. Rates of irregular spotting were similar in both groups, while amenorrhea was more frequent with LNG -IUS and weight gain and acne were numerically more common with dienogest, although these differences were not statistically significant. Device expulsion occurred only in the LNG -IUS group. Treatment discontinuation or removal was significantly more frequent in the LNG -IUS group than in the dienogest group (32.0% vs 4.0%, p<0.001), suggesting lower tolerability or acceptability of LNG-IUS in a subset of patients (Table 5). Table 5: Comparison of adverse effects between treatment groups Adverse effect Dienogest (n=50) LNG-IUS (n=50) p value Irregular spotting 21 (42.0%) 20 (40.0%) 1.000 Amenorrhea 8 (16.0%) 17 (34.0%) 0.065 Weight gain 7 (14.0%) 3 (6.0%) 0.317 Headache 5 (10.0%) 5 (10.0%) 1.000 Acne 5 (10.0%) 1 (2.0%) 0.204 Device expulsion 0 (0.0%) 4 (8.0%) 0.117 Treatment discontinuation/removal 2 (4.0%) 16 (32.0%) <0.001 Pregnancy during follow-up 0 (0.0%) 0 (0.0%) Overall clinical response at 12 months At 12 months, pain response was favorable in both groups, with a higher proportion of marked pain response in the dienogest arm, although the difference was not statistically significant (84.0% vs 72.0%, p=0.266). In contrast, menstrual blood loss response clearly favored LNG -IUS, with a significantly higher proportion of marked responders (82.0% vs 48.0%, p=0.002). Overall clinical response was good in 46.0% of the dienogest group and 60.0% of the LNG -IUS group, without a statistically significant between-group difference (p=0.229) (Table 6). Table 6: Clinical response categories at 12 months Outcome Dienogest (n=50) LNG-IUS (n=50) p value Pain response at 12 months: Marked 42 (84.0%) 36 (72.0%) 0.266 Pain response at 12 months: Minimal 0 (0.0%) 1 (2.0%) Pain response at 12 months: Moderate 8 (16.0%) 13 (26.0%) Menstrual blood loss response at 12 months: Marked 24 (48.0%) 41 (82.0%) 0.002 Menstrual blood loss response at 12 months: Minimal 4 (8.0%) 2 (4.0%) Menstrual blood loss response at 12 months: Moderate 22 (44.0%) 7 (14.0%) Overall clinical response at 12 months: Good 23 (46.0%) 30 (60.0%) 0.229 Overall clinical response at 12 months: Partial 27 (54.0%) 20 (40.0%) Summary of findings In relation to the primary objectives of the trial, both dienogest and LNG -IUS were effective in controlling symptoms of adenomyosis over 12 months. Dienogest demonstrated better reduction in dysmenorrhea, whereas LNG -IUS was more effective in reducing menstrual blood loss and junctional zone thickness on ultrasonography. Adverse -effect patterns differed between the two modalities, and treatment discontinuation or removal was more common with LNG-IUS.

In this randomized controlled trial, both dienogest and the levonorgestrel-releasing intrauterine system (LNG -IUS) were effective in improving the major symptoms of adenomyosis over 12 months of treatment. However, the pattern of benefit differed between the two modalities. Dienogest produced greater improvement in pain -related outcomes, whereas LNG -IUS showed a stronger effect on menstrual blood loss and somewhat greater ultrasonographic regression. The adverse -effect profile also differed between the groups, emphasizing that treatment selection in adenomyosis should be individualized according to the dominant symptom and the patient’s tolerance for specific side effects. The superior pain control observed with dienogest in the present study is consistent with the known role of progestins in suppressing inflammation, reducing local estrogenic activity, and alleviating adenomyosis -associated dysmenorrhea [11]. Recent pooled evidence further supports this finding. In an in - depth meta-analysis of 14 studies involving 637 patients, Lin et al. reported that dienogest significantly improved dysmenorrhea, with a mean reduction of approximately 6 points on a 10 -point visual analog scal e; the magnitude of benefit was greater in women with more severe baseline pain and with longer treatment duration [8]. Similarly, long-term prospective data from Osuga et al. demonstrated progressive reduction in pain severity during 52 weeks of dienogest therapy, with mean pain score changes of −3.4 at 24 weeks and −3.8 at 52 weeks [15]. Hirata et al. also showed that dienogest significantly reduced adenomyosis-associated pelvic pain in a pilot study, supporting its role as an effective medical option for symptomatic disease [16]. Against this background, the greater reduction in pain scores seen in the dienogest arm of the present study appears clinically plausible and is in line with the available literature [8, 15, 16]. With respect to menstrual blood loss, the present study found greater improvement in the LNG-IUS group. This observation is supported by prior evidence showing that intrauterine International Journal of Clinical Obstetrics and Gynaecology https://www.gynaecologyjournal.com ~ 900 ~ levonorgestrel is particularly effective in controlling adenomyosis-associated heavy menstrual bleeding. In one of the earlier prospective studies, Fedele et al . reported marked and safe relief from adenomyosis -associated menorrhagia after LNG-IUS insertion, with improvement in menstrual pattern and significant increases in hemoglobin, hematocrit, and ferritin during follow-up [9]. Review evidence has similarly emphasized that LNG -IUS is extremely effective in resolving abnormal uterine bleeding and can also reduce uterine volume during long-term management [11]. In contrast, although dienogest is effective for pain, bleeding-related adverse events are frequently encountered during treatment. Kobayashi noted that abnormal uterine bleeding is the most common adverse event associated with dienogest and may be particularly relevant in women with diffuse disease, advanced reproductive age, severe dysmenorrhea, elevated CA125, or low hemoglobin levels [14]. Accordingly, the stronger reduction in menstrual blood loss in the LNG -IUS arm in the present study is concordant with the broader clinical literature [9, 11, 14]. The comparative pattern seen in the current trial also mirrors the

of controlled comparative studies. Ota et al ., in a controlled clinical trial of 157 women with adenomyosis, found that both LNG -IUS and dienogest reduced pain scores, but dienogest offered greater efficacy for pain control at 3 months, while patterns of bleeding differed between the groups over longer follow-up [10]. In that study, the days of bleeding after 12 months were significantly decreased with dienogest compared with LNG -IUS [10]. This point deserves careful interpretation when comparing across studies. The present study assessed menstrual blood loss rather than only duration of bleeding, and our findings suggest that LNG -IUS provided superior control of blood loss burden. This distinction is important because amount of bleeding and number of bleeding days are not interchangeable clinical endpoints, particularly in adenomyosis where irregular spotting and altered bleeding patterns may coexist. The recent review by Habiba et al . also highlighted that the relationship between adenomyosis and abnormal uterine bleeding remains methodologically difficult to characterize because of heterogeneity in diagnostic criteria, inconsistent measurement of blood loss, and frequent coexistence of other gynecologic conditions [12]. Thus, differences between studies may reflect variation in endpoint definition as much as variation in treatment effect [10, 12]. The ultrasonographic findings in the present study add a further dimension to treatment comparison. Both groups demonstrated improvement in imaging parameters during follow-up, but LNG- IUS showed somewhat greater regression in sonographic disease burden. This is compatible with existing reviews suggesting that LNG-IUS may reduce uterine volume in the longer term [11]. Ota et al. observed that reduction in whole uterine body volume after treatment was transient in different adenomyosis subtypes, indicating that imaging regression may occur but may not always parallel sustained symptom relief [10]. For this reason, the ultrasonographic advantage of LNG -IUS in the present study should be interpreted as supportive rather than decisive; symptom control remains the central therapeutic goal, and imaging change should be considered alongside clinical improvement rather than in isolation. Adverse effects differed meaningfully between the two treatment groups in the present study. The dienogest arm showed a pattern consistent with known progestin -related bleeding disturbances, whereas the LNG-IUS arm was characterized more by device-related events such as expulsion, removal, or irregular bleeding after insertion. This again reflects prior literature. Kobayashi’s review emphasized that bleeding -related adverse events are highly characteristic of dienogest therapy [14]. Osuga et al. reported metrorrhagia in 96.9% of women receiving long - term dienogest, although most events were tolerable and serious adverse events were not observed [15]. Hirata et al . similarly found that worsening anemia due to metrorrhagia occurred in some patients during dienogest treatment [16]. On the other hand, Fedele et al. documented both expulsion and elective removal of LNG-IUS in women treated for adenomyosis -associated menorrhagia [9]. Therefore, the adverse -event differences observed in the present study are consistent with established experience and highlight the practical importance of counselling patients about expected treatment -specific side effects before initiation [9, 14-16]. From a clinical standpoint, the present findings support a symptom-oriented approach to medical management of adenomyosis. Review articles have stressed that there is no universally accepted guideline -endorsed single best medical treatment for all patients with adenomyosis, and treatment decisions should instead be guided by symptom profile, reproductive plans, uterine characteristics, and tolerance of adverse events [11]. When dysmenorrhea and chronic pelvic pain are dominant, dienogest may be especially attractive because of its consistent analgesic benefit [8,14 -16]. Conversely, when heavy menstrual bleeding is the leading complaint, LNG -IUS may offer better control and the added advantage of local therapy with less systemic exposure [9,11]. The current trial therefore reinforces the principle that the two therapies should not be viewed as directly interchangeable in all patients, but rather as options with overlapping yet distinct strengths. The present study should also be viewed in the context of emerging and alternative conservative therapies for adenomyosis. High -intensity focused ultrasound (HIFU), for example, has shown promising results in reducing dysmenorrhea and uterine volume, with meta -analytic evidence suggesting improvement in symptoms and quality of life after treatment [13]. However, the current evidence base for HIFU is limited by nonuniform studies and the absence of comparative randomized trials against standard conservative therapies [13]. In contrast, both dienogest and LNG -IUS already have a stronger practical footing in routine care, and the comparison between them remains clinically relevant because many patients require long - term symptom control while wishing to avoid hysterectomy. Certain limitations should be considered while interpreting the present findings. First, the follow -up duration of 12 months is adequate for assessing short -term and medium -term response, but it does not address longer-term durability, continuation rates, or recurrence after discontinuation. Second, ultrasonographic change, although useful, may not fully capture disease burden or correlate perfectly with symptoms. Third, bleeding outcomes in adenomyosis remain intrinsically difficult to standardize across studies, as emphasized in recent review literature [12]. Nevertheless, the randomized comparative design and the parallel assessment of pain, menstrual blood loss, imaging response, and adverse effects strengthen the clinical relevance of the present analysis. In conclusion, both dienogest and LNG -IUS were effective in the symptom control of adenomyosis, but they differed in their dominant areas of benefit. Dienogest was more effective for pain relief, whereas LNG -IUS provided better control of menstrual blood loss and somewhat greater ultrasonographic improvement. The adverse -effect patterns also differed substantially between the modalities. These findings support individualized treatment selection based on the patient’s predominant sympto m complex, International Journal of Clinical Obstetrics and Gynaecology https://www.gynaecologyjournal.com ~ 901 ~ imaging findings, and tolerance of treatment-related side effects. Further larger comparative studies with longer follow -up are warranted to clarify long -term continuation, recurrence patterns, and the optimal sequencing of conservative therapies in adenomyosis [8, 10, 12, 14].

1. Guo SW. Cracking the enigma of adenomyosis: an update on its pathogenesis and pathophysiology. Reproduction. 2022;164(5):R101-R121. 2. Bourdon M, Santulli P, Marcellin L, Maignien C, Maitrot - Mantelet L, Bordonne C, et al . Adenomyosis: an update regarding its diagnosis and clinical features. J Gynecol Obstet Hum Reprod. 2021;50(10):102228. 3. Farquhar C, Brosens I. Medical and surgical management of adenomyosis. Best Pract Res Clin Obstet Gynaecol. 2006;20(4):603-616. 4. Akhigbe RE, Afolabi OA, Adegbola CA, Akhigbe TM, Oyedokun PA. Comparison of the effectiveness of levonorgestrel intrauterine system and dienogest in the management of adenomyosis: A systematic review and meta-analysis. Eur J Obstet Gynecol Reprod Biol. 2024;300:230-239. 5. Ozdegirmenci O, Kayikcioglu F, Akgul MA, Kaplan M, Karcaaltincaba M, Haberal A, et al . Comparison of levonorgestrel intrauterine system versus hysterectomy on efficacy and quality of life in patients with adenomyosis. Fertil Steril. 2011;95(2):497-502. 6. Krentel H, De Wilde RL. Prevalence of adenomyosis in women undergoing hysterectomy for abnormal uterine bleeding, pelvic pain or uterine prolapse: A retrospective cohort study. Ann Med Surg (Lond). 2022;78:103809. 7. Stratopoulou CA, Donnez J, Dolmans MM. Conservative management of uterine adenomyosis: medical vs. surgical approach. J Clin Med. 2021;10(21):4878. 8. Lin S, Chen Y, Yi J, Xie X, Liu X, Guo SW. Dienogest treatment of symptomatic adenomyosis: An in -depth meta- analysis. Eur J Obstet Gynecol Reprod Biol. 2025;305:365 - 374. 9. Fedele L, Bianchi S, Raffaelli R, Portuese A, Dorta M. Treatment of adenomyosis -associated menorrhagia with a levonorgestrel-releasing intrauterine device. Fertil Steril. 1997;68(3):426-429. 10. Ota I, Taniguchi F, Ota Y, Nagata H, Wada I, Nakaso T, et al. A controlled clinical trial comparing potent progestins, LNG-IUS and dienogest, for the treatment of women with adenomyosis. Reprod Med Biol. 2021;20(4):427-434. 11. Vannuccini S, Luisi S, Tosti C, Sorbi F, Petraglia F. Role of medical therapy in the management of uterine adenomyosis. Fertil Steril. 2018;109(3):398-405. 12. Habiba M, Guo SW, Benagiano G. Adenomyosis and abnormal uterine bleeding: review of the evidence. Biomolecules. 2024;14(6):616. 13. Marques ALS, Andres MP, Kho RM, Abrao MS. Is high - intensity focused ultrasound effective for the treatment of adenomyosis? A systematic review and meta -analysis. J Minim Invasive Gynecol. 2020;27(2):332-343. 14. Kobayashi H. Efficacy, adverse events, and challenges of dienogest in the management of symptomatic adenomyosis: a comparison with different hormonal treatments. Gynecol Obstet Invest. 2023;88(2):71-80. 15. Osuga Y, Watanabe M, Hagino A. Long -term use of dienogest in the treatment of painful symptoms in adenomyosis. J Obstet Gynaecol Res. 2017;43(9):1441 - 1448. 16. Hirata T, Izumi G, Takamura M, Saito A, Nakazawa A, Harada M, et al. Efficacy of dienogest in the treatment of symptomatic adenomyosis: a pilot study. Gynecol Endocrinol. 2014;30(10):726-729. How to Cite This Article Das S, Das B, Patra KK. Comparative efficacy of dienogest versus levonorgestrel-releasing intrauterine system in the symptom control of adenomyosis: A randomized controlled trial . International Journal of Clinical Obstetrics and Gynaecology. 2026;10(2): 894-901. Creative Commons (CC) License This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution -Non Commercial-Share Alike 4.0 International (CC BY -NC-SA 4.0) License, which allows others to remix, tweak, and build upon the work non -commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.