Objective: Endometriosis affects up to 10% of women of reproductive age, and the main goal of treatment is to relieve symptoms. Progestins have been the mainstay of endometriosis suppression, of which dienogest has become an important option in many parts of the world. This is an expert literature review, with recommendations on the use of dienogest in the context of various clinical considerations when treating endometriosis.Methods: A search of PubMed was conducted for papers published between 2007 and 2019 on the use of dienogest in endometriosis. Experts reviewed these and included those they considered most relevant in clinical practice, according to their own clinical experience.Results: Evidence regarding the long-term use (>15 months) of dienogest for the management of endometriosis is presented, with experts concluding that the efficacy of dienogest should be assessed primarily on its impact on pain and quality of life. Fertility preservation, the option to avoid or delay surgery, and managing bleeding irregularities that can occur with this treatment are also considered. Counseling women on potential bleeding risks before starting treatment may be helpful, and evidence suggests that few women discontinue treatment for this reason, with the benefits of treatment outweighing any impact of bleeding irregularities.Conclusions: Overall, the evidence demonstrates that dienogest offers an effective and tolerable alternative or adjunct to surgery and provides many advantages over combined hormonal contraceptives for the treatment of endometriosis. It is important that treatment guidelines are followed and care is tailored to the woman's individual needs and desires.

Use of dienogest in endometriosis : a narrative literature review and expert commentary

Aims The aim of this official guideline published and coordinated by the German Society of Gynaecology and Obstetrics (DGGG) in cooperation with the Austrian Society for Gynaecology and Obstetrics (OEGGG) and the Swiss Society for Gynaecology and Obstetrics (SGGG) was to provide consensus-based recommendations for the diagnosis and treatment of endometriosis based on an evaluation of the relevant literature. Methods This S2k guideline represents the structured consensus of a representative panel of experts with different professional backgrounds commissioned by the Guideline Committee of the DGGG, OEGGG and SGGG. Recommendations Recommendations on the epidemiology, aetiology, classification, symptomatology, diagnosis and treatment of endometriosis are given and special situations are discussed.

Diagnosis and Treatment of Endometriosis. Guideline of the DGGG, SGGG and OEGGG (S2k Level, AWMF Registry Number 015/045, August 2020).

Dienogest and the Risk of Endometriosis Recurrence Following Surgery: A Systematic Review and Meta-analysis.

Dienogest (DNG) is a progestin with highly selective progesterone activity and minimal androgenic activity and is helpful in reducing endometriosis-related pain. This study assessed the long-term efficacy and safety and recurrence rate of endometrioma with DNG use beyond 12 months of treatment. A retrospective cohort study was conducted with data collected from 7 university-affiliated hospitals and included a total of 514 women with ovarian endometrioma. All patients received 2 mg of oral DNG daily for at least 48 weeks postoperatively. During continuation of DNG, the recurrence rate of ovarian endometrioma on ultrasound, adverse events, changes in menstrual pattern, and pain score (visual analogue scale) were analyzed. The average period of DNG administration in this study was 72.2 ± 5.2 weeks (range: 48-164). The recurrence rate of endometrioma was 1.8% (9 of 514), and the median duration to recurrence was 58 weeks (range: 24-76). Pain was described as overall improved by 82.2% of patients; 61.6% stated the pain was "improved" and 20.6% reported "much improved." The mean VAS score was 4.9 at baseline and significantly decreased to 2.68, 2.2, 1.6, and 2.6 at 12, 24, 48, and 96 weeks. Amenorrhea rate was 58.3% in the first 12 weeks and increased to 86.4% at 72 weeks. Prolonged daily administration of 2 mg DNG followed by surgery was associated with a lower recurrence rate of ovarian endometrioma and a reduced pain score and symptoms.

Efficacy and Safety of Long-Term Use of Dienogest in Women With Ovarian Endometrioma

Efficacy of levonorgestrel releasing intrauterine system as a postoperative maintenance therapy of endometriosis: A meta-analysis

To assess the effect of dienogest on recurrence of ovarian endometriomas and severity of pain after laparoscopic surgery, a retrospective study of 81 patients was performed at three institutions in Osaka, Japan. Patients had a six-month minimum follow-up after laparoscopic surgery for ovarian endometriomas performed between June 2012 and August 2014. Patients who chose to receive 2 mg dienogest daily and those who were managed expectantly postoperatively were included. Recurrence was defined as the presence of endometriomas of more than 2 cm. A visual analog scale (VAS) was used to score the intensity of pelvic pain. The cumulative recurrence rate and absolute VAS score changes between the baseline and at 6, 12, 18 and 24 months after the start of administration were evaluated in both groups. The recurrence rate was 16.5% and 24.0% in the expectant management group at 12 and 24 months, respectively. No recurrences occurred in the dienogest treatment group. The rate of VAS score reduction was significantly higher in the dienogest than in the expectant management group. Dienogest is effective on the recurrence of ovarian endometrioma and relieving pelvic pain after laparoscopic surgery.

Postoperative administration of dienogest for suppressing recurrence of disease and relieving pain in subjects with ovarian endometriomas.

Preterm delivery (PTD) remains a serious challenge in perinatology. Intrauterine infection and/or inflammation, followed by increased inflammatory cytokines, represented by IL-6, are involved in this pathology. Our aim was to identify IL-6-producing cells in the placenta and to analyze the potential of targeting IκB kinase β (IKKβ) signaling to suppress IL-6 production for the treatment of PTD. Immunohistochemical analyses using placentas complicated with severe chorioamnionitis revealed that IL-6 is mainly expressed in human amniotic mesenchymal stromal cells (hAMSCs). Primary hAMSCs were collected, and strong IL-6 expression was confirmed. In hAMSCs, the treatment of tumor necrosis factor-α or IL-1β drastically induced IL-6 production, followed by the phosphorylation of IKKs. A novel IKKβ inhibitor, IMD-0560, almost completely inhibited IL-6 production from hAMSCs. Using an experimental lipopolysaccharide-induced PTD mouse model, the therapeutic potential of IMD-0560 was examined. IMD-0560 was delivered vaginally 4 hours before lipopolysaccharide administration. Mice in the IMD-0560 (30 mg/kg, twice a day) group had a significantly lower rate of PTD [10 of 22 (45%)] without any apparent adverse events on the mice and their pups. In uteri collected from mice, IMD-0560 inhibited not only IL-6 production but also production of related cytokines, such as keratinocyte-derived protein chemokine/CXCL1, macrophage inflammatory protein-2/CXCL2, and monocyte chemoattractant protein-1/chemokine ligand 2. Targeting IKKβ signaling shows promising effects through the suppression of these cytokines and can be explored as a future option for the prevention of PTD.

Targeting Inhibitor of κB Kinase β Prevents Inflammation-Induced Preterm Delivery by Inhibiting IL-6 Production from Amniotic Cells

Psammocarcinoma is a serous peritoneal tumor arising from the ovary or the peritoneum and characterized by low-grade nuclear features, extensive psammoma bodies, and invasiveness Only 62 cases have ever been documented, 30 primary peritoneal and 32 primary ovarian, most of which presented as small tumors Adjuvant therapies, including chemotherapy and radiation, were performed in 12 of the primary peritoneal cases, without any clear evidence of benefit We present a case of an unusually large primary peritoneal psammocarcinoma with unexpected outcome The patient was a 38-year-old woman with a tumor of the peritoneum which adhered densely to the uterus and rectum and developed into the intra-abdominal cavity and retroperitoneal space After adhesiolysis of the tumor and rectum, suboptimal surgical reduction left a 4 cm × 2 cm tumor segment Postoperative chemotherapy, consisting of paclitaxel and carboplatin (TC) for 1 course, and cyclophosphamide and cisplatin (CP) for 5 courses, was conducted The residual tumor responded completely to the chemotherapy and the patient is alive today, with no evidence of disease 15 months after the surgery Our case implies that CP therapy is a potential regimen of postoperative remission-induction therapy for suboptimally resected primary peritoneal psammocarcinoma

Enormous cystic tumor of peritoneal psammocarcinoma exhibiting complete response to Cisplatin and cyclophosphamide after suboptimal cytoreduction: case report and review of the literature.

Atsushi Tokuhira

Papers

Postoperative administration of dienogest for suppressing recurrence of disease and relieving pain in subjects with ovarian endometriomas.

Targeting Inhibitor of κB Kinase β Prevents Inflammation-Induced Preterm Delivery by Inhibiting IL-6 Production from Amniotic Cells

Enormous cystic tumor of peritoneal psammocarcinoma exhibiting complete response to Cisplatin and cyclophosphamide after suboptimal cytoreduction: case report and review of the literature.