Long-term treatment for endometriosis with dienogest: efficacy, side effects and tolerability.

BACKGROUND: Dienogest (DNG) improves endometriosis-associated pain (EAP) and patients' quality of life; however, the modern cornerstone of the management of endometriosis is the long-term adherence of the patient to medical treatment. OBJECTIVE: To evaluate DNG as a long-term treatment of endometriosis, focusing on patients' compliance and side effects, also correlating with different phenotypes of endometriosis. METHODS: This was a cohort study on a group of patients with endometriosis (n = 114) undergoing long-term treatment with DNG. During the follow up visits (12, 24, and 36 months) patients were interviewed: an assessment of EAP was performed by using a visual analogue scale (VAS) and side effects were evaluated by using a specific questionnaire of 15 items. RESULTS: At 12 months, 81% were continuing the DNG treatment, with a significant reduction of dysmenorrhea, dyspareunia, dyschezia, dysuria and chronic pelvic pain. Of the 19% that discontinued the treatment: 62% was due to spotting, reduced sexual drive, vaginal dryness, and mood disorders. The improvement of EAP was significant for all endometriosis phenotypes, especially in patients with the deep infiltrating type. At 36 months, 73% of patients were continuing the treatment, showing a significant reduction of EAP through the follow up, along with an increase of amenorrhea (from 77% at 12 months to 93% at 36 months). In a subgroup of 18 patients with gastrointestinal disorders, DNG was administered vaginally at the same dosage, showing similar results in terms of efficacy and tolerability. CONCLUSIONS: DNG was an effective long-term treatment for all endometriosis phenotypes, with few side effects that caused the discontinuation of the treatment mainly during the first year. Thus, the course of 1-year treatment is a predictive indicator for long-term treatment adherence.

The effects of dienogest and combined oral contraceptives on protein S-specific activity in endometriosis patients.

OBJECTIVE: One serious side effect of combined oral contraceptives (COCs) is venous thromboembolism. Reduced activity in activated protein C-related coagulation pathways is attributable to low protein S activity in one-third of Japanese patients with deep vein thrombosis. Herer, we quantified the behavior of protein S-specific activity in response to dienogest (DNG) and COCs using the protein S-specific activity assay system to explore its potential utility as a thrombosis marker. STUDY DESIGN: This was a prospective cohort study. Female patients aged 20 - 49 years who were starting drug treatment for endometriosis using DNG or COCs were enrolled. Blood samples were taken before treatment and at the first, third, and sixth months of treatment. To analyze the primary endpoints, changes in total protein S antigen levels, total protein S activity, and protein S-specific activity from baseline to each time point were estimated using a linear mixed-effects model. All statistical analyses were performed in the SAS software version 9.4 (SAS Institute, Cary, NC). A two-sided P < 0.05 was considered statistically significant. RESULTS: 64 patients took DNG and 34 patients took COCs. Protein S-specific activity did not change significantly from baseline in the six months after treatment started in either group. In the DNG group, total protein S activity and total protein S antigen levels increased slightly from baseline levels after the treatment. The means for total protein S activity and total protein S antigen levels in the COC group remained within reference limits, but they both decreased markedly in the first month and stayed low. Protein S-specific activity in four women remaind below the reference limit throughout the whole study period, suggesting they may have potential protein S deficiencies. CONCLUSION: The effects of DNG on protein S were negligible, though both total protein S activity and antigen levels decreased soon after COC treatment began and remained low. As there was no VTE event during the study, further studies with larger numbers of patients will be needed to confirm that protein S-specific activity can be a surrogate maker of VTE risk.

NLRP3 concentration, oxidants, and antioxidants in plasma of endometriosis patients undergoing treatment with dienogest.

OBJECTIVE: NOD-like receptor pyrin domain-containing 3 (NLRP3) is a cytosolic multi-protein complex that induces inflammation and is negatively regulated by progesterone. Previous researches have reported abnormal induction of reactive oxygen species (ROS) and progesterone resistance in endometriosis (EM). Since progesterone regulates ROS level and, consequently, inflammation, our objective is to investigate whether dienogest (DNG) regulates NLRP3 and whether the regulation of NLRP3 inflammasome by DNG in the blood plasma of patients with EM can affect oxidant and antioxidant markers. METHODS: Plasma samples were obtained from control and EM patients experiencing pain symptoms to measure the level of NLRP3, oxidants, and antioxidants. Subsequently, these patients were given oral DNG 2 mg/day for six months for drug treatment. After six months, plasma samples were collected from the patients for re-examination. RESULTS: The findings indicate that DNG reduced NLRP3 concentration and oxidant production while increasing antioxidant production in blood plasma. By reducing NLRP3, DNG was able to alleviate inflammation and pain caused by inflammation in EM patients. CONCLUSION: In conclusion, the use of DNG in EM patients resulted in a decrease in NLRP3 concentration in the patient's plasma. Furthermore, this effect was enhanced by balancing oxidant/antioxidant levels, which may contribute to reducing inflammation associated with EM.

Dienogest attenuates STAT3 activation in ovarian endometriotic cysts.

OBJECTIVE: Recent studies have suggested that endometriosis could be the result of excessive activation of signal transducer and activator of transcription 3 (STAT3), which is associated with the regulation of essential cellular mechanisms such as proliferation, invasion, and apoptosis. That finding implies that regulating STAT3 activation could play a key role in treating endometriosis. In the present study, we aimed to evaluate whether the anti-endometriotic effects of dienogest is mediated by the regulation of STAT3 activation. STUDY DESIGN: STAT3 activation was evaluated in normal endometrial and ovarian endometriotic tissues obtained from patients with/without preoperative dienogest treatment. A subsequent in vitro analysis with endometriotic cyst stromal cells (ECSCs) was used to confirm the direct influence of dienogest in STAT3 activation. RESULT: STAT3 activation is significantly higher in endometriotic tissues from non-treated patients than in normal endometrial tissues, and that difference is reversed by preoperative administration of dienogest. Similarly, the inhibitory effects of dienogest on STAT3 activation are demonstrated by in vitro results showing that dienogest treatment significantly inhibits IL-6-stimulated STAT3 activation in cultured ECSCs. That inhibition was accompanied by decreased expression of proliferative (PCNA), invasive (MMP-2), and anti-apoptotic (BCL-2) proteins. Furthermore, downregulating STAT3 activity with siRNA decreased PCNA, MMP-2, and BCL-2 expression in IL-6-treated ECSCs. CONCLUSION: Dienogest inhibits STAT3 activation in ECSCs, which affects their proliferation, invasiveness, and apoptosis.

Microfluidics-derived hierarchical microparticles for the delivery of dienogest for localized endometriosis therapy.

Drug therapy is one of the most important strategies for treating gynecological diseases. Local drug delivery is promising for achieving optimal regional drug exposure, considering the complex anatomy and dynamic environment of the upper genital tract. Here, we present microparticle-based microcarriers with a hierarchical structure for localized dienogest (DNG) delivery and endometriosis treatment. The microparticles were fabricated by microfluidics and consisted of photo-crosslinked bovine serum albumin hydrogel particles (D@P-B MPs) encapsulating DNG-loaded PLGA (poly lactic-co-glycolic acid) microspheres. Such design enables the microparticles to have sustained release capacity and cell adhesion ability. Based on this, the microparticles were applied for the treatment of peritoneal endometriosis through intraperitoneal injection. The performance of the microparticles in inhibiting the growth of ectopic lesions as well as their anti-inflammatory, anti-angiogenesis, and pelvic pain-relieving effects are well demonstrated in vivo. These findings indicate that the present hierarchical microparticles are good candidates for localized treatment of endometriosis and are promising for the management of gynecological diseases. STATEMENT OF SIGNIFICANCE: We prepared photo-crosslinked bovine serum albumin hydrogel particles (D@P-B MPs) encapsulating DNG-loaded PLGA microspheres using microfluidic electrospray. Such hierarchical structure provided multiple functions of the particles as drug carriers. The hierarchical microparticles not only supported the sustained release of drugs but also provided adhesion to human ectopic endometrial stromal cells. The hierarchical microparticles represented a localized treatment method for endometriosis and is promising for the management of gynecological diseases.

Venous Thromboembolic Risk of Estradiol Valerate-Dienogest Compared with Ethinyl Estradiol-Levonorgestrel Combined Oral Contraceptives.

This pooled analysis compared the risk of venous thromboembolism (VTE) associated with combined oral contraceptives (COCs) containing estradiol (E2) valerate-dienogest with those containing ethinyl E2-levonorgestrel. Data were retrieved from two large, prospective, observational cohort studies. Propensity score subclassification was applied to balance baseline parameters between the COC user cohorts. Crude and adjusted hazard ratios (HRs) were calculated based on the extended Cox model. The pooled data set included 11,616 E2 valerate-dienogest users and 18,681 ethinyl E2-levonorgestrel users, contributing 17,932 and 29,140 women-years of observation, respectively. A significantly decreased VTE risk in E2 valerate-dienogest COCs compared with ethinyl E2-levonorgestrel COCs was observed (propensity score-stratified HR 0.46, 95% CI, 0.22-0.98). This pooled analysis expands data from a previous postauthorization safety study and provides valuable real-world safety information on the relative safety of current COCs.

A Bioequivalence Trial of Dienogest in Healthy Chinese Participants Under Fed Conditions.

This trial was a randomized, open-label, single-dose, 2-treatment, 2-period, crossover study to evaluate the pharmacokinetic (PK) profile, bioequivalence, and safety of test formulation and reference formulation of 2-mg dienogest tablets in healthy Chinese participants. Eligible participants were randomly administered a single 2-mg dose of either the test formulation or the reference formulation orally under fed conditions, followed by a 1-week washout period and the administration of the other formulation. Samples of blood were collected until 48 hours following administration. The main PK parameters were calculated using noncompartmental analysis techniques. The main PK parameters included maximum plasma concentration, area under the plasma concentration-time curve (AUC) from time zero to the last quantifiable concentration, and AUC from time zero to infinity. The bioequivalence of test and reference dienogest tablets was determined if the 90% confidence intervals of the geometric mean ratio of the test to reference formulations were within the predefined range of 80%-125%. The safety assessment included incidence of adverse events and serious adverse events and others. Twenty-four healthy Chinese participants were enrolled in this trial. The geometric mean ratios of maximum plasma concentration, AUC from time zero to the last quantifiable concentration, and AUC from time zero to infinity between the 2 formulations, and corresponding 90% confidence intervals, all fell within the range of 80%-125% under fed conditions. The test and reference dienogest tablets were well tolerated, and no severe adverse events were reported in the trial. It was shown that the test and the reference dienogest tablets were bioequivalent and well tolerated under fed conditions in healthy Chinese female participants.

Dienogest does not augment the gene expression of adhesion molecules, MCP-1, and monocyte adherence in human endothelial cells.

OBJECTIVE: Medroxyprogesterone acetate (MPA) may increase the risk of atherosclerosis during hormone replacement therapy (HRT); therefore, the effect of progestogens other than MPA on atherosclerotic lesions requires evaluation. Adhesion of monocytes to vascular endothelial cells is an important early step in atherosclerosis progression. MCP-1 is a key chemokine that promotes monocyte migration and adhesion to vascular endothelial cells. In this study, we investigated the effects of dienogest (DNG), an alternative progestogen, on monocyte adhesion and cytokine expression in human umbilical vein endothelial cells (HUVECs). STUDY DESIGN: HUVECs were treated with DNG, natural progesterone, or MPA, followed by interleukin (IL)-1ß stimulation. The mRNA expression of adhesion molecules (E-selectin and ICAM-1) and cytokines (MCP-1 and IL-6) was examined using real-time PCR. A flow chamber system was used to examine the effect of DNG on the adhesion of U937 monocytic cells to monolayer HUVECs. RESULTS: Unlike MPA, DNG did not alter the mRNA expression of E-selectin, ICAM-1, MCP-1, and IL-6 in HUVECs. Moreover, it did not increase the number of monocytes adhering to HUVECs in the flow chamber system. However, MPA treatment significantly enhanced monocyte adhesion to HUVECs (p < 0.05). CONCLUSIONS: DNG had no effect on the mRNA expression of adhesion molecules and cytokines in HUVECs, as well as the monocyte adhesion to HUVECs, suggesting that DNG can be explored as an alternative to MPA for HRT.

Segmented in vitro fertilization and frozen embryo transfer in dienogest-treated patient with adenomyosis: A case report and lierature review.

OBJECTIVE: To assess the effects of dienogest on segmented in vitro fertilization (IVF) and frozen-thawed embryo transfer (FET) for a patient with adenomyosis. CASE REPORT: A 33-year-old female with primary infertility for 3 years had dysmenorrhea and hypermenorrhea. Diagnosis of adenomyosis was made with a sonographic exam and an elevated cancer antigen 125 (CA-125, 310 U/mL). Her early follicular hormone profile (anti-müllerian hormone, AMH, 8 ng/mL) was normal. After repeated controlled ovarian stimulation (COS) and failed intrauterine insemination (IUI), she underwent IVF. Controlled ovarian stimulation using gonadotropin-releasing hormone (GnRH) antagonist protocol was performed with the blastocyst freeze-all IVF cycle. Pretreatment with two months of GnRH agonist (GnRHa) and frozen-thawed embryo transfer did not result in pregnancy. Subsequently, three months of long-term pretreatment with dienogest was given, and the CA-125 level was markedly reduced. Frozen-thawed blastocyst stage embryo transfer was provided, and a singleton pregnancy was achieved. CONCLUSION: Dienogest, a novel progestin highly selective for progesterone receptors, may benefit the pregnancy outcomes of infertile patients with adenomyosis adopting segmented IVF with FET.

Efficacy of Post-Operative Medication to Prevent Recurrence of Endometrioma: Cyclic Oral Contraceptive (OC) After Gonadotropin-Releasing Hormone (GnRH) Agonist Versus Dienogest.

BACKGROUND: There are several medical treatment options for endometrioma. Progestin, especially dienogest, is an effective drug for preventing recurrence of endometrioma after surgery. Additionally, oral contraceptive (OC) use after conservative surgery has been reported to reduce significantly the risk of endometrioma recurrence. The aim of this study was to compare the long-term effects of gonadotropin-releasing hormone (GnRH) agonist followed by OC to those of dienogest alone to prevent recurrence of endometrioma after laparoscopic surgery. METHODS: A retrospective cohort study was performed on patients who underwent conservative laparoscopic surgery for endometrioma between January 2000 and December 2020, in the Endometriosis Clinic, Department of Gynecology, Samsung Medical Center. A total of 624 patients who received medical treatment at least six months after laparoscopic conservative surgery for endometrioma was included. Among them, 372 patients used OC after GnRH agonist therapy, and 252 patients used dienogest. Within the OC group, 148 used a 21/7 regiment and 224 used a 24/4 regimen. A cumulative endometrioma recurrence curve was presented using the Kaplan-Meier method to compare the recurrence of those groups. RESULTS: The cumulative recurrence rate of endometrioma for 60 months was 2.08% (n = 4) in the OC after GnRH agonist group and 0.40% (n = 1) in the dienogest group. There was no statistical difference in cumulative recurrence of endometrioma between the two groups. In subgroup analysis, the cumulative recurrence rate of endometrioma over 60 months was 4.21% (n = 2) in the 21/7 OC group and 1.09% (n = 2) in the 24/4 OC group and showed no significant difference. CONCLUSION: Long-term use of OC after GnRH agonist as well as that of dienogest treatment are effective postoperative medical therapies for preventing endometrioma recurrence. Thus, the choice of regimen can be individualized or used interchangeably depending on patient condition, need for contraception, and compliance with drug therapy.

Long-term treatment of dienogest with symptomatic adenomyosis: retrospective analysis of efficacy and safety in clinical practice.

Objective: To evaluate the efficacy and safety of dienogest (DNG) in women with symptomatic adenomyosis.Methods: Women with symptomatic adenomyosis were included in this retrospective observation study. Group 1 (maximum uterine dimension ≥ 100.0 mm) began DNG after 4 months of GnRH-a administration, Group 2 (maximum uterine dimension < 100.0 mm) received DNG with no prior GnRH-a treatment. All women were assessed for their pain symptoms, uterine size, adverse effects and laboratory hematology at baseline and every 6 months during the treatment.Results: 123 women were enrolled in this study, in Group 1 (71 women) with severe uterine enlargement, the median VAS score was 80 mm prior to GnRH-a administration and 10, 10, 10, 20, and 20 mm, respectively, after 0, 6,12,18, and 24 months of DNG treatment. The mean uterine volume decreased from 262.9 ml to 104.7 ml after GnRH-a therapy, and slowly increased from 104.7 ml to 139.5 ml after 24 month-treatment of DNG. Another 52 women with mild uterine enlargement received DNG without prior GnRH-a administration, median VAS score was 70 mm at baseline and decreased to 20, 20, 10, and 10 mm at 6,12,18, and 24 months. The mean uterine volume slightly decreased from 157.9 ml to 153.3 ml after 24 months of DNG treatment (p > 0.05). All laboratory parameters were in the normal range.Conclusions: DNG is effective and well tolerated as a long-term treatment for symptomatic adenomyosis, and it can be used as maintenance therapy after discontinuation of GnRH-a administration.

The dienogest-related cystitis in women with endometriosis: a prospective, controlled, comparative study.

The aim of the study was to examine the severity of clinical symptoms of acute cystitis and the level bacteriuria in female patients who underwent to laparoscopic surgery followed by a postoperative administration of dienogest 2 mg and combined oral contraceptives pills (COCP). One hundred and forty five women who had a laparoscopic surgery prospectively were enrolled. Criteria inclusions were the age from 30 to 45 years old; body mass index (BMI) absence of previous hormonal therapy at least 6 month and recent performed a laparoscopy surgery for endometriosis. The women (n = 35) who had uterine myoma, abnormal coagulation profile; concomitant neoplastic diseases; chronic pelvic inflammatory disease and chronic recurrent cystitis were excluded from study. The female patients were assigned into both groups treatment: group I (n = 54) and group II (control, n = 56) who received dienogest 2 mg once daily and COCP, respectively. During follow-up three female patients of group I were withdrawn due to prolonged genital bleedings. The final analysis included 105 women. The patients of both groups had a low level of bacteriuria <103 CFU/ml without clinical symptoms of acute cystitis before treatment. The level of bacteriuria in-group I significantly increased from 102 to 106 CFU/ml whereas in-group II did not exceed 102 CFU/ml during 4 weeks of hormonal treatment. The differences of values of acute cystitis symptom score (ACSS) for differential, typical, quality of life domains were statistically significant after 4, 8 and 12 weeks of therapy in-group I compared with group II. During 3 months of hormonal treatment with dienogest 2 mg in group I, the acute cystitis developed in 10 (18.5%), in 19 (38%) and in 34 (68%) women at 4, 8 and 12 weeks of follow-up, respectively. All cases of acute cystitis in-group I were successfully treated with fosfomycin trometamol 3 g single dose or nitrofurantoin 50 mg four times a day during 5 days. We concluded that the dienogest might increase the level bacteriuria and severity of clinical symptoms of acute cystitis during a postoperative prophylaxis of endometriosis.Impact statementWhat is already known on this subject? Dienogest is a 19-nortestosterone derivative progestogen that is highly selective for progesterone receptors with high efficacy for reducing endometriosis-related pelvic pain syndrome. The administration of dienogest is a standard treatment option after laparoscopic excision of endometrial heterotopic tissue with prophylactic purpose. However, there are some adverse events, which are a cause for discontinuation.What do the results of this study add? Despite the low incidence of urinary tract infection (1-5.4%) reported in different studies this study has shown that there was a significant increase of level bacteriuria and severity of clinical symptoms of cystitis in the dienogest group.What are the implications of these findings for clinical practice and/or further research? The implications of these findings are that the administration of dienogest may lead to enhancing of clinical symptoms of cystitis and increasing bacteriuria in some women after operative treatment of endometriosis.

Randomized study on the effectiveness of nomegestrol acetate plus 17ß-estradiol oral contraceptive versus dienogest oral pill in women with suspected endometriosis­associated chronic pelvic pain.

BACKGROUND: To evaluate the effects of a combined oral contraceptive containing 1.5 mg 17b-estradiol (E2) and 2.5 mg nomegestrol acetate (NOMAC) or 2 mg/daily dienogest (DNG) oral progestin on endometriosis-associated chronic pelvic pain (CPP) and on the quality of life (QoL) and sexual function, by a randomized study design. METHODS: The E2/NOMAC group and DNG group included 99 and 98 women, respectively. The levels of CPP were measured by the visual analogic scale (VAS). The QoL scores were investigated by the Short Form-36 questionnaire (SF-36). Finally, sexual function was studied using the Female Sexual Function Index (FSFI), while sexual distress was studied by the Female Sexual Distress Scale (FSDS). The study had 3, 6 and 12-month follow-ups. RESULTS: The intra-group analysis showed an improvement of the VAS score from baseline to the 12-month follow-up in the women of both groups (p < 0.001). The inter-group comparison showed a similar improvement of CPP (p = 0.06). Women on DNG had better SF-36 somatic (p < 0.01) and FSFI scores (p < 0.006) than women on E2/NOMAC at the 6- and 12-month follow-ups. CONCLUSIONS: The results support the efficacy of both hormonal treatments, even if DNG was more effective than E2/NOMAC in a limited intergroup comparison.

A prospective study examining the effect of dienogest treatment on endometrioma size and symptoms.

OBJECTIVE: We aimed to determine the effect of dienogest on cyst volume, symptoms, and quality of life in patients with endometrioma. METHOD: This prospective cohort study included 37 patients diagnosed with endometrioma and planned for medical treatment. Subjects were treated with a 3-month oral dose of dienogest 2 mg/day. Pre-treatment and post-treatment endometriosis measurements were assessed via 3D ultrasonography, pain symptoms via 100-mm visual analog scale (VAS), and quality of life via Short Form-36. RESULTS: The mean age of the patients was 36.0 ± 6.6 years. The mean endometrioma volume was significantly reduced by 31% after treatment (26.7 ± 19.7 mm3) compared to the pre-treatment volume (17.4 ± 11.2 mm3, p < .001). Post-treatment VAS scores of dysmenorrhea, dyspareunia, and chronic pelvic pain VAS values were significantly decreased by 35.5% (p < .001), 37.5% (p < .001), and 38.5% (p < .001), respectively. The mean physical function score and mental health score significantly increased by 15% (p = .009) and 28% (p < .001), respectively. CONCLUSION: Our findings showed dienogest treatment at oral doses of 2 mg/day for 3 months significantly reducing the size of endometrioma, reducing pain level, and increasing quality of life in women with endometriosis.

Impact of Long-Term Dienogest Therapy on Quality of Life in Asian Women with Endometriosis: the Prospective Non-Interventional Study ENVISIOeN.

Several clinical trials in women with endometriosis demonstrated that dienogest reduces endometrial lesions and improves health-related quality of life (HRQoL). To assess HRQoL in dienogest-treated patients in real-world setting, we conducted a prospective, non-interventional study in 6 Asian countries. Women aged ≥18 years with clinical or surgical diagnosis of endometriosis, presence of endometriosis-associated pelvic pain (EAPP) and initiating dienogest therapy were enrolled. The primary objective was to evaluate HRQoL using the Endometriosis Health Profile-30 (EHP-30) questionnaire. The secondary objectives included analysis of EAPP, satisfaction with dienogest, endometriosis symptoms and bleeding patterns. 887 patients started dienogest therapy. Scores for all EHP-30 scales improved with the largest mean changes at month 6 and 24 in scale pain (-28.9 ± 27.5 and - 34 ± 28.4) and control and powerlessness (-23.7 ± 28.2 and - 28.5 ± 26.2). Mean EAPP score change was -4.6 ± 3.0 for both month 6 and 24 assessments. EAPP decrease was similar in surgically and only clinically diagnosed patients. From baseline to month 24, rates of normal bleeding decreased (from 85.8% to 17.5%) while rates of amenorrhea increased (from 3.5% to 70.8%). Majority of patients and physicians were satisfied with dienogest. Over 80% of patients reported symptoms improvement. 39.9% of patients had drug-related treatment-emergent adverse events, including vaginal hemorrhage (10.4%), metrorrhagia (7.3%) and amenorrhea (6.4%). In conclusion, dienogest improves HRQoL and EAPP in the real-world setting in women with either clinical or surgical diagnosis of endometriosis. Dienogest might be a promising first-line treatment option for the long-term management of debilitating endometriosis-associated symptoms.NCT02425462, 24 April 2015.

A cohort study of the efficacy of the dienogest and the gonadotropin-releasing hormone agonist in women with adenomyosis and dysmenorrhea.

PURPOSE: To study the efficacy and safety of the dienogest and the gonadotropin-releasing hormone agonist (GnRH-a) in symptomatic females with uterine adenomyosis. METHODS: A total of 127 patients with adenomyosis with a chief complaint of dysmenorrhea were recruited. The first group received 2 mg of dienogest (DNG) daily, whereas the second group received goserelin acetate (GS) (3.6 mg/4 weeks) for 12 weeks. Outpatient follow-up was undertaken after 12 weeks. RESULTS: Among 127 women, 56/63 (88.9%) patients completed the treatment in the DNG group, whereas 62/64 (96.9%) patients completed the treatment in the GS group. A significant decrease in dysmenorrhea symptoms as measured by the visual analog scale (VAS) and Carcinoma antigen125 (CA125) after 12 weeks of treatment was observed in both groups (p < .001). The hemoglobin of anemic patients did not significantly improve after 12 weeks of treatment (p＝0.21) and the uterine volume slightly increased without statistical significance (p＝0.10) in the DNG group. Simultaneously, The hemoglobin of anemic patients significantly improved (p < .001) and the uterine volume significantly decreased (p < .001) in the GS group. CONCLUSIONS: Dienogest effectively alleviates the symptoms of dysmenorrhea in patients with adenomyosis, but it cannot improve the anemia or reduce the size of the uterus. GnRH-a is more effective in improving anemia and reducing the uterine volume in patients with adenomyosis. TRIAL REGISTRATION: ChiCTR1900024958.