Long-term dienogest treatment in endometriosis: Consensus from Taiwanese experts.

Dienogest has been proven effective as long-term therapeutic option for pelvic pain caused by endometriosis. However, in Taiwan, there is a lack of a well-tailored consensus on its long-term administration. To address this gap, Taiwanese experts in collaboration with the Taiwan Endometriosis Society (TES), convened to provide structured recommendations on dienogest treatment and monitoring strategies. Drawing from clinical evidence and collective expertise, the experts formulated individualized treatment strategies based on treatment objectives and the patient's demographics. The experts recommend long-term dienogest administration for endometriosis patients for appropriate symptom control while reducing the risk of disease recurrence. Specifically, they recommend regular ultrasound examinations and relevant blood tests to monitor disease progression and therapeutic response with additional breast screening for patients at high risk for breast cancer. These recommendations aim to provide physicians with comprehensive guidance on the long-term administration of dienogest for endometriosis, ensuring patient safety and optimizing treatment outcomes.

[Efficacy and safety of dienogest on ovarian endometrioma].

Objective: To observe the effects and safety of dienogest on the volume and symptoms of ovarian endometrioma (OMA). Methods: The clinical data of 75 patients with OMA who underwent treatment with dienogest (2 mg/day) at the First Affiliated Hospital of Nanjing Medical University from July 1st 2020 to March 31st 2024 were retrospectively analysed, mainly comparing the changes in the volume of OMA and the visual analogue scale (VAS) scores of endometriosis-related pain before and after the treatment, as well as observing the changes in the blood biological indicators, liver and kidney function, coagulation function and changes in breast. Results: The median cyst volumes of the OMA patients at 3, 6 and 12 months of dienogest treatment were 13.21 cm3 (volume reduction rate: 36.00%), 8.33 cm3 (volume reduction rate: 56.00%) and 4.10 cm3 (volume reduction rate: 77.62%), respectively, which were all significantly decreased from the pre-treatment period (all P<0.05). The VAS scores of pain of the OMA patients at 3, 6 and 12 months of dienogest treatment all were 0 mm. Blood cancer antigen 125 (CA125) and cancer antigen 19-9 (CA19-9) levels decreased progressively during treatment (all P<0.05). There were no statistical differences in the coagulation indexes, liver and kidney function indexes of the patients during dienogest treatment compared with those before treatment (all P>0.05). During the follow-up period, there were a few patients with changes in the growth sites or lesion category of the breast nodules, but there were no occurrence of breast cancer or precancerous lesions. Conclusion: Dienogest is effective in reducing OMA volume and alleviating endometriosis-related pain with few adverse effects.

Clinical efficacy of dienogest against endometriomas with a maximum diameter of ≥4 cm.

OBJECTIVE: This prospective observational study aims to demonstrate the clinical efficacy of dienogest in treating endometriomas with a maximum diameter of ≥4 cm. METHODS: Patients (n = 81) with endometriomas (diameter of ≥4 cm) were enrolled and administered orally with dienogest (2 mg daily) and followed up for a year [Ethical approval code: 2020 Research 343]. Further, the efficacy was determined by recording the largest diameter and volume of the endometriomas, uterine volume, endometrial thickness, and the largest diameter of uterine fibroids in the patients during 0, 6, and 12 months. The pain symptoms were assessed using the Numerical Rating Scale (NRS), and the side effects of medication were monitored. With the consent, some patients underwent routine blood tests, and serum hormone, as well as Anti-Müllerian Hormone (AMH) levels were measured. RESULTS: The dienogest treatment resulted in a significant reduction of the maximum diameter of these cysts from 50.5 mm to 41 mm in 6 months and 34 mm in 12 months. In addition, the volume of the cysts significantly decreased from 37.8 ml from baseline to 18.5 ml in 6 months and 11.8 ml in 12 months. Among 26 subjects with ultrasonic signs of endometrial polyps, 92.3% of cases displayed no polyps after 12 months. No significant changes were observed in the size of uterine fibroids and AMH levels. The NRS score showed a decrease from an average of 6.6-1.2 in 12 months. CONCLUSION: Dienogest could effectively reduce the diameter and volume of endometriomas with a maximum diameter of ≥4 cm, improving anemia, as well as pain symptoms and preserving ovarian function.

Evaluation of the therapeutic efficacy of high-intensity focused ultrasound ablation combined with different drugs in the treatment of adenomyosis.

OBJECTIVES: To observe the therapeutic efficacy of high-intensity focused ultrasound (HIFU) combined with different pharmacological treatments for adenomyosis. MATERIALS AND METHODS: A total of 126 patients with adenomyosis who underwent HIFU combined with pharmacological treatment were retrospectively reviewed. Patients were treated with either dienogest (DNG) (Group A, N = 38) or GnRH-a (Group B, N = 88) for three months after HIFU, and received levonorgestrel-releasing intrauterine systems (LNG-IUS) at the end of the third month. Visual Analog Scale (VAS) and Pictorial Blood Loss Assessment Chart (PBAC) scores were used for evaluating symptom improvement. RESULTS: After propensity score matching (1:2), 38 patients were included in Group A and 76 in Group B. All patients showed significant improvement in VAS and PBAC scores after HIFU, but the PBAC score of Group A was significantly higher than that of patients in Group B at 18 months [11.50 (1.00, 29.50) vs. 0.00 (0.00, 16.50), p < 0.01] and 24 months [4.00 (0.25, 27.75) vs. 0.00 (0.00, 12.75), p = 0.04] after HIFU. Furthermore, patients in Group B had a greater uterine volume reduction at 24 months after HIFU than that of patients in Group A [51.00 (27.00, 62.00) vs. 30.00 (17.00, 42.75, p = 0.02)]. However, the adverse effects in Group A were lower than those in Group B [7 (15.79) vs. 35 (46.05), p < 0.01]. No significant difference was observed in the recurrence rate between the two groups. CONCLUSIONS: HIFU combined with DNG and LNG-IUS is a safe and effective treatment for patients with adenomyosis.

Different Effect of Dienogest on Endometrium Mesenchymal Stem Cells Derived from Healthy and Endometriosis Tissues

Background: Endometriosis (EM) is an inflammatory condition in which the endometrium is observed to develop outside the uterine cavity. Endometrium has conventionally been recognized as a rich source of endometrial mesenchymal stem cells (E-MSCs). The influence of dienogest, a medication frequently prescribed for EM, on E-MSCs has not been extensively investigated. Aims: To explore effects of dienogest on the E-MSCs derived from healthy (E-MSCs-control) and diseased (E-MSCs-endometriosis) endometrial tissue samples in vitro. Study Design: In vitro study. Methods: We collected samples from healthy and diseased endometrial tissues. E-MSCs were derived from both healthy and EM tissues. The effect of dienogest (VISANNE) on E-MSCs was assessed by examining cell proliferation, telomerase activity, cell migration, and estrogen secretion levels after the isolation and characterization of E-MSCs. Results: We discovered that cellular proliferation rate was higher in the E-MSCs derived from EM tissues compared to those derived from healthy tissue. The proliferation rate and telomerase activity were both suppressed by dienogest treatment, particularly in E-MSCs-endometriosis. The drug treatment also resulted in a decrease in the migration capacity of E-MSCs-endometriosis, from 60.4% to 59.2%. The expression of CXCL12, Ki67, and beta-catenin was analyzed in both E-MSCs-endometriosis and E-MSCs-control. The CXCL12 and Ki67 expressions were quite elevated in the E-MSCs-endometriosis without drug treatment compared to the E-MSCs-control. Following the treatment, these levels declined drastically to the levels close to E-MSCs-control. Similarly, this decrease in gene expression was accompanied by a decrease in estrogen secretion into the medium. Conclusion: This research demonstrates that dienogest exerts a substantial impact on both stromal and stem cells, as it effectively controls the disease by reversing EM markers, despite the absence of progesterone receptors on endometrial stem cells.

A systematic review and Bayesian analysis of the adverse effects of dienogest.

BACKGROUND AND OBJECTIVE: Endometriosis and adenomyosis are two common diseases that impair women's health, and dienogest is one of the pharmacologic treatments which is the first-line therapeutic option for patients with pelvic pain and individuals who have no desire for immediate pregnancy. The goal of this study was to summarize the current evidence of adverse events associated with dienogest as well as the prevalence of these adverse events during treatment with dienogest. METHODS: Several databases (PubMed, Embase, Cochrane Central and Clinicaltrials.gov, etc.) and the US FDA Adverse Event Reporting System (FAERS) Public Dashboard were searched on May 31, 2023, using the topic words alongside free words of dienogest and "adverse reaction". Studies were incorporated into this research if they reported or assessed safety issues or adverse reactions of dienogest during the period of endometriosis treatment or adenomyosis therapy. The extracted information comprised trial design, dienogest and control group demographics, as well as reported side effects. RESULTS: This systematic review comprehended 39 publications in total. The mean age of patients in the included studies was 34.43 years. The follow-up duration varied from 3 to 60 months. Most adverse reactions were common and not serious, and the most common adverse reactions during dienogest medication were abnormal uterine bleeding (55%, 95% CI 37-73%), amenorrhea (17%, 95% CI 2-42%) and swelling (13%, 95% CI 3-28%). Uncommon adverse reactions included dysmenorrhea (0.2%, n = 1), dyspepsia (0.4%, n = 1), and (lower) abdominal pain (1%, 95% CI 0-3%), urticaria (1%, 95% CI 0-3%) and peritonitis (1%, n = 1). Serious adverse reactions including decreased lumbar spine Bone Mineral Density (BMD), depression, peritonitis and so on have been reported. Heterogeneity assessment revealed that patient number and study design are influencing factors to adverse reaction prevalence. Moreover, abdominal pain, diarrhea, nausea and vomiting, back pain and anemia are side effects reported both in the FAERS database and in the systematic review. CONCLUSIONS: Dienogest's most frequent side effects were not severe. Dienogest is generally safe for treating endometriosis and adenomyosis. Nevertheless, people should be aware of serious adverse reactions, such as decreased lumbar spine BMD and hemorrhagic shock.

Levonorgestrel intrauterine system versus dienogest effect on quality of life of women with deep endometriosis: a randomized open-label clinical trial.

Women with deep infiltrating endometriosis (DIE) can benefit from the use of progestins. Our aim is to explore if levonorgestrel-releasing intrauterine system (LNG-IUS) non inferior to dienogest (DNG) in improving deep endometriosis women's quality of life (QoL). This randomized open-label clinical trial included forty women with DIE assessed using clinical history and physical examination, transvaginal ultrasonography and magnetic resonance of the pelvis without any previous surgical treatment, with two treatments arms. The two groups underwent a 3-month washout of hormonal treatments, and then received either DNG or LNG-IUS for 6 months. QoL was assessed prior to and 6 months after the intervention, using the SF36 and the EHP30. DNG and LNG-IUS showed an increase on all domains of the SF36 (p < .001). There was no difference between treatments on the improvement observed (p > .05 for all domains). DNG and LNG-IUS, also, showed improvement on all domains of EHP30 (p < .001), except "relationship with children" and "feelings about pregnancy." However, there was no statistical difference between treatments for all sections scores (p > .05). The treatment of deep endometriosis symptoms using either DNG or LNG-IUS in women with no prior surgical treatment is associated with improvement in QoL.Trial Registration Number: This trial is registered on "The Brazilian Registry of Clinical Trials (ReBECID: RBR-8fjx2jp)," that is part of Primary Registries in the WHO Registry Network, under the title: "Dienogest versus Levonorgestrel IUS on deep endometriosis patient´s QoL without surgery" on June 14, 2021; https://ensaiosclinicos.gov.br/rg/RBR-8fjx2jp.

Medical management of endometriosis.

PURPOSE OF REVIEW: While laparoscopic surgery plays a key role in the management of endometriosis, symptoms commonly recur, and repeat surgery comes with increased risk. Medical management, including hormonal and nonhormonal treatment, is vital in managing painful symptoms. This review summarizes recent evidence regarding various medical management options available to treat pelvic pain associated with endometriosis. RECENT FINDINGS: Efficacy of dienogest vs. combined oral contraceptive on pain associated with endometriosis: randomized clinical trial.Once daily oral relugolix combination therapy vs. placebo in patients with endometriosis-associated pain: two replicate phase 3, randomised, double-blind, studies (SPIRIT 1 and 2).A randomized, double-blind, placebo-controlled pilot study of the comparative effects of dienogest and the combined oral contraceptive pill in women with endometriosis.Two-year efficacy and safety of relugolix combination therapy in women with endometriosis-associated pain: SPIRIT open-label extension study. SUMMARY: All symptomatic women with suspected endometriosis who are not desiring immediate fertility can be offered suppressive treatment to control symptoms and slow the progression of disease. First-line treatments include the combined oral contraceptive pill and progestogens. Second-line treatments include gonadotropin-releasing hormone agonists and antagonists but current guidelines recommend that these should be reserved for people whose symptoms fail to be controlled by first-line agents. The use of complementary and alternative medicines is also increasing in both volume and number of agents used.

Comparison of dienogest or combinations with ethinylestradiol/estradiol valerate on the pain score of women with endometriosis: A prospective cohort study.

Endometriosis is one of the most frequent gynecologic disorders. The pathognomonic symptom of endometriosis is pelvic pain. The recommended pain medications are oral hormonal contraceptives, progestin therapy, danazol, gonadotropin-releasing hormone analogs, nonsteroidal anti-inflammatory drugs, and aromatase inhibitors. In this study, we aimed to compare the efficiency of costing dienogest (DNG) and low-cost oral contraceptives regarding visual analog scores (VAS) score of pelvic pain and also cancer antigen-125 (CA-125), anti-Mullerian hormone (AMH) levels, and size of endometrioma in the patients with endometriosis which is a chronic disease that requires a lifelong management plan. In our study, 18 to 45-year-old patients presented to our institution's gynecology and obstetrician department for various complaints over 2 years, and endometriosis diagnoses were included. Patients were divided into 3 groups (20 patients in each medication group) according to the given medication: cyclic DNG (Visanne) or 0.03 mg ethinylestradiol combined with 2 mg DNG (Dienille) or estradiol valerate combined with 2 mg DNG (Qlarista). We recorded all patients' CA-125/AMH values and VAS scores of pelvic pain. All patients gave informed consent. There was no statistically significant difference between pre-medication and post-medication levels of CA-125, AMH, VAS score, and cyst size in all groups. However, statistically, significant decreases were seen in the cyst size and VAS score, indicating response to therapy in all groups. In conclusion, we think it is more reasonable to use cost-effective oral contraceptive medications, which also cause common side effects, instead of costing DNG since all drugs have the same efficiency and success.

Comparison of the effectiveness of levonorgestrel intrauterine system and dienogest in the management of adenomyosis: A systematic review and meta-analysis.

BACKGROUND: Adenomyosis is a gynaecological lesion that impairs female fertility and contributes to reduced quality of life. There are several surgical and medical options for the management of this lesion; however, women who wish to conceive opt for medical therapies such as the levonorgestrel intrauterine device (LNG-IUS) and dienogest, which have various outcomes. To date, there is no consensus regarding which is more effective. OBJECTIVES: To compare the effectiveness of LNG-IUS and dienogest for the management of adenomyosis, and explore the risk of occurrence of known side effects for both treatments. DESIGN: Systematic review and meta-analysis exploring the effectiveness of LNG-IUS and dienogest for the management of adenomyosis. METHODS: A literature search was conducted using PICO guidelines and EMBASE, PubMed/MEDLINE, Scopus and Web of Science databases. Only clinical trials were collected and analysed. RESULTS: Of the 792 studies that were initially identified, six were eligible for inclusion in this study. The studies included a total of 707 women; of these, 270 were treated with LNG-IUS, 354 were treated with dienogest, and 83 were controls. All the studies were from Asia (Bangladesh n = 1, China n = 2, India n = 1, Japan n = 1, South Korea n = 1). Dienogest was found to reduce pelvic pain significantly, evidenced by a lower visual analogue scale score, compared with LNG-IUS. Also, dienogest led to a significant reduction in uterine volume compared with LNG-IUS. However, subjects in the LNG-IUS group had significantly higher levels of haemoglobin than those in the dienogest group. Nonetheless, the occurrence of side effects such as weight gain, breast tenderness/distension, headache, insomnia/sleep disorder, depression/mood disorder, skin disorder/acne, and coital discomfort/reduced libido were comparable in both treatment groups. CONCLUSION: Dienogest may be more effective than LNG-IUS for the management of adenomyosis, as it shows a superior effect in the reduction of pelvic pain and uterine volume. As only six studies were included in the present meta-analysis due to the paucity of data in the literature, it is recommended that well-designed randomized controlled trials comparing the effectiveness of dienogest with LNG-IUS should be conducted.

Dienogest treatment in women with endometriosis: A retrospective cohort study in Taiwan.

OBJECTIVE: To assess the treatment efficacy of dienogest specifically in the Taiwanese population with endometriosis. MATERIALS AND METHODS: Eighty-eight patients diagnosed with endometriosis receiving at least 3 months of dienogest 2 mg once daily, from January 2018 to June 2022, were enrolled. They were divided into two groups: surgery group and non-surgery group. The assessment of pain improvement was based on visual analog scale (VAS) scores (0-100 mm) recorded at 0, 3, 6, and 12 months following the initiation of dienogest. Serum CA-125 value and ovarian endometrioma size were analyzed at 0 and 6 months. RESULTS: A total of 65 patients with endometriosis presented painful symptoms. In the surgery group (N = 28), the initial VAS score was 47.5 mm, which significantly declined to 9.6 mm at 3 months (p < 0.01), then to 7.5 mm, 2.9 mm, and 2.1 mm at 6, 9, and 12 months, respectively. In the non-surgery group (N = 37), the initial VAS score was 65.7 mm, which significantly declined to 13.2 mm at 3 months (p < 0.01) and 4.9 mm at 6 months (p < 0.05), remained low at 0.3 mm at both 9 and 12 months. Endometrioma size (N = 33) exhibited a significant 35% decrease from 38.2 mm to 24.8 mm after 6 months treatment (p < 0.01). Serum CA-125 levels showed significant improvement from 86.5 to 30.2 U/ml (p < 0.01) at 6 months. CONCLUSION: This retrospective cohort study proved that dienogest is effective in reducing endometriosis-associated pain and endometrioma size in Taiwanese population.

The use of dienogest in treatment of symptomatic adenomyosis: A systematic review and meta-analysis.

Adenomyosis is a gynaecological problem that impacts women's quality of life by causing dysmenorrhea, chronic pelvic pain, and menorrhagia. The search continues for the best medical treatment for symptomatic adenomyosis. This systematic review and meta-analysis investigated the role of dienogest, an oral progestin, in reducing pain and bleeding associated with adenomyosis. Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, MEDLINE, Scopus, and Web of Science were searched in January 2024. The primary outcome was pain scores for dysmenorrhea, whereas secondary outcomes were chronic pelvic pain (CPP), uterine volume (UV), and menorrhagia. One comparison was performed comparing outcomes in symptomatic adenomyosis before and after treatment with dienogest. Pooled analysis of included studies reported a statistically significant reduction of dysmenorrhea pain score after dienogest treatment (mean difference -5.86 cm on a 10-cm visual analogue scale, 95 % CI -7.20 to -4.53, I2 = 97 %). Regarding chronic pelvic pain, a meta-analysis of included studies showed a significant decline in pain after treatment (standardized mean difference -2.37, 95 % CI -2.89 to -1.86, I2 = 60 %). However, uterine volume did not differ significantly after treatment (mean difference -4.65 cm3, 95 % CI -43.22 to 33.91). Menorrhagia was improved significantly after treatment (Peto odds ratio 0.07, 95 % CI 0.03 to 0.18). In conclusion, dienogest seems to be effective in controlling painful symptoms and uterine bleeding in women with adenomyosis at short and long-term therapy.

Long-term therapy with dienogest or other oral cyclic estrogen-progestogen can reduce the need for ovarian endometrioma surgery.

BACKGROUND: Almost 10% of women in reproductive age are diagnosed with ovarian endometriomas and can experience symptoms and infertility disorders. Ovarian endometriomas can be treated with medical or surgical therapy. OBJECTIVE: To assess whether long-term therapy with dienogest or oral cyclic estrogen-progestogens is effective in reducing the size of ovarian endometriomas, alleviating associated symptoms, and reducing the requirement for surgery. DESIGN: Prospective non-interventional cohort study. METHODS: We enrolled childbearing women diagnosed with ovarian endometriomas. We collected demographic, clinical, and surgical data, including the evaluation of ovarian endometrioma-associated symptoms and pain using the visual analog scale. We grouped the women according to treatment regimen into dienogest, estrogen-progestogens, and no-treatment. Patient's assessment was performed at baseline and after 12 months evaluating the largest ovarian endometrioma diameter (in millimeters) and the associated symptoms. Furthermore, we analyzed the impact of hormonal treatment in a sub-group of women fulfilling at baseline the criteria for a first-line surgical approach (ovarian endometrioma > 30 mm with visual analog scale > 8 or ovarian endometrioma > 40 mm before assisted reproductive treatments or any ovarian endometrioma(s) > 60 mm). RESULTS: We enrolled 142 patients: 62, 38, and 42 in dienogest, estrogen-progestogens, and no-treatment groups, respectively. No significant differences were found regarding baseline characteristics. After 12 months, the mean largest ovarian endometrioma diameter increased in the no-treatment group (31.1 versus 33.8; p < 0.01), while a significant reduction was registered in the dienogest (35.1 versus 25.8; p < 0.01) and estrogen-progestogens (28.4 versus 16.7; p < 0.01) groups; no significant difference in ovarian endometrioma diameter reduction between these two latter groups was noted (p = 0.18). Ovarian endometrioma-associated symptoms and pain improved in dienogest and estrogen-progestogens groups, with a significantly greater effect for dienogest than for estrogen-progestogens for dysmenorrhea (74% versus 59%; p < 0.01). In the sub-group of women eligible for first-line surgery at baseline, long-term treatment with dienogest and estrogen-progestogens reduced surgical eligibility by 30%. CONCLUSIONS: Decreased mean largest ovarian endometriomas'diameter after 12 months and reduction of the need for surgical treatment by 30% were observed in dienogest and estrogen-progestogens groups. Long-term treatment with dienogest had a greater effect in alleviating dysmenorrhea and pain.

Hormonal Therapies before in vitro fertilization in women with endometriosis: The Minotaur's Labyrinth and the Ariadne's Thread.

Endometriosis-related infertility is one of the most debated topics in reproductive medicine. In recent years, prolonged pre-cycle hormonal regimens gained attention as a mean of improving the assisted reproduction technologies (ART) success rates in endometriosis patients. GnRH agonists, dienogest, medroxyprogesterone acetate, and aromatase inhibitors are the most studied medications. Conflicting results and a high risk of bias exist in almost all of the conducted studies in the field. However, current evidence suggests that pre-cycle treatment with GnRH agonists may be beneficial for patients with stage III/IV endometriosis. Dienogest and medroxyprogesterone acetate-based progestin-primed ovarian stimulation protocol was shown to be comparable to the prolonged GnRH agonists protocol. Finally, aromatase inhibitors seem to be of limited benefit to the assisted reproductive outcomes of endometriosis patients. Although it is challenging to draw any clinical conclusions, pre-cycle hormonal treatments seem to be best indicated in endometriosis patients who had previously failed ART treatment.

CGRP neuropeptide levels in patients with endometriosis-related pain treated with dienogest: a comparative study.

BACKGROUND AND OBJECTIVE: Endometriosis (EM) involves the peripheral nervous system and causes chronic pain. Sensory nerves innervating endometriotic lesions contribute to chronic pain and influence the growth phenotype by releasing neurotrophic factors and interacting with nearby immune cells. Calcitonin gene-related peptide (CGRP), a pain-signaling neurotransmitter, has a significant role. This study examines the effect of Dienogest (DNG), a hormone therapy used for managing EM -related pain, on serum CGRP levels in EM patients. MATERIALS AND METHODS: The Visual Analog Scale (VAS) assessed pain in diagnosed EM. INDIVIDUALS: Serum samples were obtained to measure CGRP concentration. Participants received a 2 mg/day oral dose of DNG for six months as prescribed treatment. Additional serum samples were collected after this period to measure CGRP levels. RESULTS: In the EM group, 6.7%, 33.3%, and 20% had ovarian EM, ovarian plus uterosacral, and ovarian plus bladder, respectively. The EM group showed higher CGRP serum levels than the control group (80.53 ± 16.13 vs. 58.55 ± 6.93, P < 0.0001). Still, after drug administration, CGRP serum levels significantly decreased compared to pre-treatment levels (69.66 ± 11.53 vs. 80.53 ± 16.13, P < 0.05). The EM group showed higher pain compared to the control group (7.93 ± 1.58 vs. 0.13 ± 0.35, P < 0.0001), but after drug administration, pain significantly decreased compared to pre-treatment levels (1.00 ± 2.00 vs. 7.93 ± 1.58, P < 0.05). CONCLUSION: DNG administration reduces pain and serum CGRP levels in EM patients, offering the potential for innovative treatments and tailored options. Understanding neurotransmitter roles and drug effects can aid in discovering more effective modulators for these pathways.

Efficacy and safety of dienogest in the treatment of deep infiltrating endometriosis: A meta-analysis.

OBJECTIVE: To systematically review and conduct a meta-analysis to assess the effectiveness of dienogest (DNG) in the prolonged conservative drug management of deep infiltrating endometriosis (DIE). The findings from this study are intended to serve as a valuable reference for clinical decision-making regarding medication in the context of DIE. METHODS: Following the PRISMA Statement, we searched EMBASE, PubMed, The Cochrane Library, Web of Science, and Medline databases for relevant literature published in the public domain from the date of establishment of the database until October 2023. Subsequently, all English publications on clinical studies using DNG for the treatment of DIE were included. Studies involving surgical intervention or drug therapy for postoperative recurrence were excluded. All literature included in the review underwent risk assessment of bias. Two evaluators independently screened the publications, conducted a quality assessment of each article and extracted data. We used Revman 5.4 for the meta-analysis of the included literature. RESULTS: Our final analysis consisted of five clinical studies, involving a total of 256 patients. We found that there were significant improvements in the following indicators post-medication as compared to levels before taking the medication: dysmenorrhea (MD = 4.24, 95 % CI: 2.92-5.56, P < 0.00001), non-menstrual pelvic pain (MD = 3.11, 95 % CI: 2.34-3.88, P < 0.00001), dyspareunia (MD = 1.93, 95 % CI: 1.50-2.37, P < 0.00001), dyschezia (MD = 2.48, 95 % CI: 1.83-3.12, P < 0.00001), and rectosigmoid nodule size (MD = 0.32, 95 % CI: 0.18-0.46, P < 0.00001). Compared with pre-medication levels, the following indicators were significantly worse: headache (RR = 0.03, 95 % CI: 0.00-0.23, P = 0.0006), decreased libido (RR = 0.08, 95 % CI: 0.01-0.62, P = 0.02); and there was no significant improvement in dysuria (P > 0.05). CONCLUSION: DNG showed efficacy in relieving pain-related symptoms and significantly reducing the size of the lesions when used in the drug conservative treatment of DIE.

The Visual Effect of a Down-Regulation With Dienogest and GnRH Analogues in Endometriosis: Lessons Learned From Two-Step Surgical Approach.

OBJECTIVE: To evaluate the intraoperative visual effect of treatment with GnRH-analogues and Dienogest in endometriosis. DESIGN: Retrospective observational study. SETTING: Every laparoscopy from all the different disciplines in our hospital is documented on video and stored in a database. The study was approved by the local ethics committee. A total of 193 patients with histological proven endometriosis from 2007 to 2021 were included, who underwent 2-step surgical procedure. Indications were endometrioma before CO2-Laser therapy, missing consent because of emergencies or other surgeries from other disciplines, or high active and extended disease. When endometriosis was suspected in a surgery conducted by other disciplines, a gynecological surgeon was called during the surgery. Data and intraoperative videos were reviewed by 2 independent reviewers at one referral center. Only cases with available video of first and second look laparoscopy were included. We excluded patient who had prior hormonal treatment in the last 6 months. Lesions were classified according to the description of Khan et al. Statistical analysis was performed using SPSS (Version 27.0, IBM). Mann-Whitney U test (nonparametric analysis) and χ2 tests were applied. Percentages were calculated for categorical variables and mean and standard deviation were calculated for continuous variables. Significance level was set to p <.05. INTERVENTIONS: Seventy-seven received GnRH-analogues and 116 Dienogest for preoperative hormone down-regulation. The median duration of down-regulation with GnRH-analogues or Dienogest was 3 months. The mean age was 32.3 (SD 6.3) years for GnRH-analogues and 32.6 (SD 6.3) years for Dienogest, p = .619 respectively. The visible intraoperative effect will be demonstrated in the video. CONCLUSION: The effect of a hormonal treatment can be observed macroscopically in endometriosis. This can help to understand the in vivo response to the administrated treatment. This video is showing our past experience, as performing second-look laparoscopy is not state of the art anymore.

The Effects of Long-Term Dienogest Therapy on In Vitro Fertilization Outcomes in Women with Endometriosis: A Systematic Review and Meta-Analysis.

OBJECTIVES: Assessing dienogest's efficacy in endometriosis patients undergoing in vitro fertilization (IVF). DATA SOURCES: Systematic search in databases (PubMed, MEDLINE, Embase, Web of Science, Cochrane CENTRAL, Google Scholar) until 1 October 2022. STUDY SELECTIONS: Randomized trials and observational studies comparing extended dienogest pre-treatment, no pre-treatment, or gonadotropin-releasing hormone (GnRH) agonist pre-treatment in endometriosis-linked IVF. OUTCOME MEASURES: live birth, clinical pregnancy rates, oocytes collected, miscarriage rate, gonadotropin consumption. DATA EXTRACTIONS AND SYNTHESES: Two authors independently assessed eligibility. Dichotomous variables were analyzed via a random-effect model and Mantel-Haenszel method to calculate weighted estimates and 95% confidence intervals (CI). I2 statistic gauged study heterogeneity; GRADE criteria evaluated evidence quality. CONCLUSIONS: Out of 191 publications, five studies with 723 participants were included. Uncertainty persists on whether prolonged dienogest affects live birth (RR 1.42, 95% CI 0.29 to 6.84; 3 studies, n = 289; I2 86%) and clinical pregnancy rates (RR 1.33, 95% CI 0.31 to 5.65; 3 studies, n = 289; I2 86%) compared to conventional IVF. Moreover, uncertainty remains regarding intervention impact on live birth (RR 1.46, 95% CI 0.63 to 3.37; 1 study, n = 34) and clinical pregnancy rates (RR 1.32, 95% CI 0.78 to 2.23; 3 studies, n = 288; I2 0%) versus long-term GnRH agonist therapy before IVF. Given limited data and very low evidence quality, doubts arise about the benefits of long-term dienogest pre-treatment before conventional IVF in endometriosis patients.