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AbstractObjectiveMethodResultsConclusionTrial registrationThis study aimed to assess the efficacy of randomly started oral dienogest/ethinylestradiol (DNG/EE) for swift endometrial preparation prior to outpatient hysteroscopic polypectomy in perimenopausal women.A multicenter, prospective, randomized controlled trial was conducted in university hospitals. Eighty perimenopausal women scheduled for outpatient hysteroscopic polypectomy between January 2023 and March 2024 were randomly assigned to either intervention (n = 40) or control (n = 40) groups. Exclusion criteria included concomitant endometrial pathologies, recent therapy and adnexal diseases. The intervention group received oral DNG/EE 2 mg/0.03 mg/day started on any day of the menstrual cycle for 14 days. The control group underwent polypectomy between menstrual cycle days 8 and 11 without pharmacological treatment.Pre-procedure (p < 0.001) and post-procedure (p < 0.001) endometrial thickness were significantly reduced in the intervention group, along with a higher incidence of hypotrophic/atrophic endometrial patterns (p < 0.001). Surgical parameters also differed significantly between groups.DNG/EE treatment offers rapid, cost-effective endometrial preparation, enhancing surgical outcomes and patient satisfaction during outpatient polypectomy.ClinicalTrials.gov NCT06316206. [ABSTRACT FROM AUTHOR]

Dysmenorrhea treatment with 0.5 mg dienogest tablets twice daily (1 mg/day) has proven useful, but its effect on premenstrual disorders has not yet been evaluated. This study aimed to evaluate the efficacy of 0.5 mg dienogest tablets in relieving premenstrual syndrome (PMS)-like symptoms during the treatment of dysmenorrhea in comparison with that of continuous low-dose estrogen–progestin (LEP/COC) drospirenone/ethinylestradiol combination, which is considered effective in treating premenstrual dysphoric disorder. During the standard course of dysmenorrhea treatment with dienogest or LEP/COC, PMS-like symptoms were scored based on patients' reports, and the treatment effects were compared. As a result, the dienogest group experienced a significant improvement in PMS-like symptoms compared with the LEP/COC group over the 6-month study period (p < 0.01). Furthermore, dienogest was more effective in providing relief from PMS-like symptoms, with 89.7% of patients reporting a complete resolution of PMS-like symptoms at 6 months, compared with 47.1% in the LEP/COC group (p < 0.01). These results indicate that dienogest is effective in relieving PMS-like symptoms, similar to LEP/COC. Further studies are needed to determine whether 0.5 mg dienogest tablets, which are only available in Japan, are effective in treating premenstrual disorders diagnosed via standard methods. [ABSTRACT FROM AUTHOR]

• Dienogest led to a significant reduction in visual analogue scale score compared with the levonorgestrel intrauterine system (LNG-IUS). • Dienogest reduced uterine volume significantly compared with LNG-IUS. • The occurrence of side effects was comparable in the dienogest and LNG-IUS groups. 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. 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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

Adenomyosis is a chronic disease associated with abnormal uterine bleeding and debilitating pain with severely reduced quality of life in many affected women. Primary strategies for its management encompass surgical interventions, hormonal therapy, or a synergistic blend of these therapeutic modalities. Dienogest (DNG), a new progestin, is primarily utilized to treat adenomyosis due to its exceptional selectivity for the progesterone receptor. In this uncommon case report, we introduce a 42-year-old woman who experienced hemorrhagic shock as a result of uterine bleeding and pulmonary embolism that occurred while a patient was undergoing dienogest therapy for uterine adenomyosis. This situation necessitated blood transfusion and introduction of drugs then an emergency hysterectomy was scheduled followed by the initiation of anticoagulation. We hypothesize that the emergence of pulmonary embolism was intimately tied to adenomyosis, and the occurrence of hemorrhagic shock was likely due to the intake of dienogest.

Dysmenorrhea treatment with 0.5 mg dienogest tablets twice daily (1 mg/day) has proven useful, but its effect on premenstrual disorders has not yet been evaluated. This study aimed to evaluate the efficacy of 0.5 mg dienogest tablets in relieving premenstrual syndrome (PMS)-like symptoms during the treatment of dysmenorrhea in comparison with that of continuous low-dose estrogen–progestin (LEP/COC) drospirenone/ethinylestradiol combination, which is considered effective in treating premenstrual dysphoric disorder. During the standard course of dysmenorrhea treatment with dienogest or LEP/COC, PMS-like symptoms were scored based on patients’ reports, and the treatment effects were compared. As a result, the dienogest group experienced a significant improvement in PMS-like symptoms compared with the LEP/COC group over the 6-month study period (p < 0.01). Furthermore, dienogest was more effective in providing relief from PMS-like symptoms, with 89.7% of patients reporting a complete resolution of PMS-like symptoms at 6 months, compared with 47.1% in the LEP/COC group (p < 0.01). These results indicate that dienogest is effective in relieving PMS-like symptoms, similar to LEP/COC. Further studies are needed to determine whether 0.5 mg dienogest tablets, which are only available in Japan, are effective in treating premenstrual disorders diagnosed via standard methods.

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

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. [ABSTRACT FROM AUTHOR]

Endometriosis (EMs) is one of the leading causes of dysmenorrhea, chronic pelvic pain and infertility in women, and the long-term management of EMs should maximize the role of drug therapy. Progestogens are the first-line drugs for the treatment of EMs, among which dienogest has now been taken as the first choice of drug for long-term management of EMs. Dienogest not only effectively relieves EMs -associated pain and prevents postoperative recurrence, but also has been observed to reduced EMs lesion volume to some extent. For young patients with ovarian endometriotic cysts who have not yet given birth, patients with recurrent ovarian endometriotic cysts, and patients with deep-infiltrating endometriosis (DIE) who experience significant pain, dienogest can reduce the volume of lesions, delay or even avoid surgery. In this review, we provide an overview of dienogest′ s impact on the volume of ovarian EMs and DIE, aiming to provide a basis for individualized nonsurgical treatment of EMs. [ABSTRACT FROM AUTHOR]

Objective: To assess the effect of dienogest treatment on endometrioma (OMA) size, serum anti-Mullerian hormone (AMH) levels and associated pain over a 12-month follow-up period. Material and Methods: A longitudinal cohort study of 104 patients with OMA who were treated with dienogest, between January 2017 and January 2020. Of the included patients, each had a 12-month follow-up period with transvaginal or pelvic ultrasound and measurement of serum AMH concentration at the sixth and twelfth months of follow-up. The alteration in OMA size in the sixth and twelfth months of treatment was the primary outcome measure and the alteration in AMH concentration over the same period was the secondary outcome measure. The only exclusion criterion was having surgical intervention for OMA during the follow-up period (n=44). In patients with bilateral OMA (n=21), the change in size of the largest OMA was considered in the analysis. Results: A total of 60 patients with a mean ± standard deviation (SD) age of 31.5±8.0 years were included. The mean ± SD OMA size on the day the dienogest was started was 46.3±17.4 mm and the mean AMH level was 3.6±2.4 ng/mL. After six months, the mean OMA size had decreased to 38.6±14.0 mm, with a median difference of 7.8 mm [95% confidence interval (CI): 3.0 to 12.6; p=0.003]. The mean AMH level was 3.3±2.7 ng/mL at 6 months follow-up (95% CI: -0.2 to 0.8; p=0.23) and the average difference was 0.3 ng/mL. At the 12th-month visit, when compared with the beginning of the treatment, OMA size had again significantly decreased by a median of -8.9 mm (95% CI: -2.9 to -14.9; p=0.005), and the decline in median AMH was also significant (-0.9 ng/mL, 95% CI: -0.1 to -1.7; p=0.045). The initial mean ± SD visual analog scale pain score at the commencement of dienogest treatment was 6.3±3.4. The mean values at the sixth and twelfth months of dienogest therapy were 1.08±1.8 and 0.75±1.5, respectively (both p<0.001 compared to baseline). Conclusion: At the sixth and twelfth months of dienogest treatment a significant decrease in OMA size and reported pain scores were observed, whereas the AMH concentrations did not change significantly. [ABSTRACT FROM AUTHOR]

• A meta-analysis of conservative treatment of DIE with DNG drugs. • DNG can effectively relieve the pain symptoms related to DIE without resorting to surgical treatment. • DNG showed significantly reducing the size of the lesions when used in the conservative treatment of DIE. 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. 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. 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). 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. [ABSTRACT FROM AUTHOR]

Analysis of literary data. In total, 41 publications by foreign authors were selected and processed. Information on the effectiveness of the domestic progestogen drug Vigest-KV in the treatment of endometriosis in our own practice is also presented. Today, the newest progestin is dienogest, a derivative of 19-nortestosterone. It has shown its high efficiency in various clinical manifestations of endometriosis, as well as in its recurrences. Long-term treatment regimens with dienogest (60 months) are promising, as they effectively reduce pain and the risk of endometriosis recurrence, in particular after surgical treatment. An important advantage of dienogest is the low frequency of side effects (1.2–2.5%), especially such as the effect on bone mineral density. Our clinical experience allows us to recommend the Ukrainian medicinal product Vigest-KV, containing dienogest, for the treatment of various types of endometriosis. Its advantage is a special mechanism of ovulation blockade aimed at apoptosis of the granulosa cells of the growing follicle. Also, long-term use of this drug leads to the inhibition of follicle-stimulating and luteinizing hormones and a moderate decrease in the estradiol, the level of which is within the physiological parameters. This is very important to avoid the symptoms of estrogen deficiency while maintaining the anti-proliferative effect. Conclusions. Today, the main method of treating endometriosis is hormone therapy. It not only reduces the clinical symptoms of endometriosis, but is also used before and after surgical treatment to reduce the risk of disease recurrence. Progestins (dienogest) are the most common hormonal method of treating endometriosis. Dienogest, as the most effective progestin, has a pronounced anti-proliferative effect directed at the endometrium, as well as anti-inflammatory and immunomodulatory effects with a minimal risk of side effects. Dienogest in a dose of 2 mg/ day provides a reduction in clinical symptoms, an improvement in the quality of life and preservation of reproductive function. Taking into account our own clinical experience of using Vigest-KV in various types of endometriosis, we can recommend its implementation into clinical practice. [ABSTRACT FROM AUTHOR]

Background: Endometriosis is a chronic gynecologic disease that is dependent on estrogen and is associated with the existence of endometrial glands and stroma outside the uterus. It has been demonstrated that dienogest significantly and fairly effectively alleviates endometriosis-related symptoms such as dysmenorrhea and irregular menstruation. Material and Methods: This was a randomized, prospective, comparative, open-label study. For 12 weeks, Group A (n=30) received Dienogest 2 mg OD while Group B (n=30) received Medroxyprogesterone acetate (MPA) 10 mg BD. The patients were assessed at 4, 8, and 12 weeks to observe the VAS Score for dysmenorrhea, number of patients having dysmenorrhea, number of patients having irregular menstrual cycles. Adverse drug reactions (ADRs) were recorded for safety assessment. Results: After 12 weeks, VAS score & number of patients experiencing dysmenorrhea decreased in both groups significantly. Dienogest depicted better response than MPA in the reduction of VAS score (95.99% versus 84.91%; p-value=0.048) & reduction in the number of patients having dysmenorrhea after 12 weeks (6.67% versus 26.67%; p-value=0.038) and the difference was statistically significant. MPA group had a greater number of ADRs. Conclusion: Dienogest is significantly more effective than MPA, especially for dysmenorrhea. Dienogest shows better tolerability than MPA.

Abstract 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

Although endometriosis is a benign disease, it is associated with cancer-related gene mutations, such as KRAS or PIK3CA. Endometriosis is associated with elevated levels of inflammatory factors that cause severe pain. In a previous study, we demonstrated that KRAS or PIK3CA mutations are associated with the activation of cell proliferation, migration, and invasion in a patient-derived immortalized endometriotic cell line, HMOsisEC10. In this study, we investigated the effects of these mutations on progesterone resistance. Since the HMOsisEC10 had suppressed progesterone receptor (PR) expression, we transduced PR-B to HMOsisEc10 cell lines including KRAS mutant and PIK3CA mutant cell lines. We conducted a migration assay, invasion assay, and MTT assay using dienogest and medroxyprogestrone acetate. All cell lines showed progesterone sensitivity with or without mutations. Regarding inflammatory factors, real-time quantitative RT-PCR revealed that the KRAS mutation cell line exhibited no suppression of Cox-2 and mPGES-1 on progesterone treatment, whereas IL-6, MCP-1, VEGF, and CYP19A1 were significantly suppressed by progesterone in both mutated cell lines. Our results suggest that KRAS mutation and PIK3CA mutation in endometriotic cells may not be associated with progesterone resistance in terms of aggressiveness. However, KRAS mutations may be associated with progesterone resistance in the context of pain.

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. [ABSTRACT FROM AUTHOR]

Purpose The first aim of this review is to provide an overview of existing literature and current knowledge of endometriosis pathogenesis, diagnosis and recommended forms of treatment. The second aim of this article is to epmhasize the role of the microbiota on the pathogenesis and treatment of endometriosis Endometriosis is a common disease. It affects 5-10% of women of reproductive age worldwide. However, despite its prevalence, diagnosis is typically delayed by years, misdiagnosis is common, and effective treatment takes years to achieve. Determining the mechanisms involved in its pathogenesis is vital, not only to pave the way for early identification, but also for disease management and development of less invasive but successful treatment strategies. Three main types of endometriosis have been described in literature: peritoneal, ovarian and deep infiltrative. This is mainly due to the most common locations of ectopic endometrium. Determining the precise pathogenesis of endometriosis has proved challenging and controversial for gynecologists, endocrinologists and researchers, but recent studies have focused on finding answers. A number of pathogenic mechanisms have been suggested to be involved in the development of endometriosis, and a large number of studies have investigated the causes of its pathogenesis. This disease is often asymptomatic and diagnosed incidentally during various surgical interventions or follow-up gynecological examinations. Women with this pathology report exhaustion and depression, as with other chronic pain conditions. However, the severity of pain doesn't always reflect the severity of endometriosis. Epidemiological research reports that women with this disease are more vulnerable to ovarian and breast cancer, asthma, skin cancer such as melanoma, cardiovascular disease and inflammatory joint diseases like rheumatoid arthritis. Due to the lack of specific symptoms diagnosis is often delayed about 6-10 years from the first symptoms. According to current gynecological recommendations, the clinical examination of patients with a suspicion of endometriosis should include inspection and palpation of the abdominal cavity, vaginal speculum, vaginal vault and a two-handed gynecological examination, best complemented by a composite study. Nowadays, geneticists are in complete agreement about the primary goals of endometriosis treatment. The most important of these are the relief or complete elimination of pain, the removal of endometriosis foci, and the fight against fertility. To date, the most commonly used therapy is combination therapy, which consists of surgical procedures such as laparoscopy, laparotomy, or cryosurgery, and adjuvant hormonal therapy, which has significantly reduced the risk of recurrence The microbiota is a diverse ecosystem of microorganisms that reside in various parts of the human organism. Specific microbiomes can be distinguished for the oral cavity, nasal cavity, ears, vagina, gastrointestinal tract, respiratory system, hair and skin. The connection between the gut microbiota and endometriosis is nowadays highly suspected to exist. Scientists are focused on the influence of the microbiome on estrogens, estrogens-dependent disorders, immune system, and inflammation. It is strongly believed that the correction of the gut microbiota with antibiotics, probiotics, or fecal bacterial transplantation is a hopeful method for improving the clinical management of endometriosis. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

• Protein S-specific activity didn't change significantly during hormonal treatments. • Protein S activity and antigen levels decreased soon with oral contraceptives. • Protein S activity and antigen levels didn't decrease with dienogest. • 4 out of 111 patients were suspected of having protein S deficiency. 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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

Umbilical endometriosis, although relatively rare, has been described with plenty of case reports and case series available in the literature. Surgical excision has been the preferred mode of treatment, with or without excision of the umbilicus. Few cases described laparoscopically assisted excision but lacked descriptions of a safe alternative non-umbilical laparoscopy entry portal, management of possible concomitant intraperitoneal lesions, and aesthetic umbilicus repair. The aim of this work is to describe a modified technique of laparoscopically assisted excision of umbilical endometriosis and treat concomitant intraperitoneal lesions via a new laparoscopic entry portal with aesthetic preservation of the umbilicus. Successful complete excision of the mass with aesthetic preservation of the umbilicus followed by 3 months of Dienogest therapy resulted in complete resolution of the mass. It is concluded that utilizing "Darwish point" for abdominal access to excise umbilical endometriosis and treat concomitant intraabdominal lesions, offers smart abdominal access with aesthetic umbilicus repair. Moreover, postoperative hormonal treatment (Dienogest) is helpful to ensure a better cure. [ABSTRACT FROM AUTHOR]

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. 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. 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. Dienogest inhibits STAT3 activation in ECSCs, which affects their proliferation, invasiveness, and apoptosis. [ABSTRACT FROM AUTHOR]

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Endometriosis is a common gynecological condition with a complex physio-pathological background. This study aimed to assess the role of Rubus idaeus leaf extract (RiDE) as a potential therapeutic agent in reducing the size of the endometriotic lesions and modulate the plasma expression of MMP-2, MMP-9, and TGF-β1. The endometriotic lesions were induced in a rat model by the autologous transplant of endometrium. Thirty-six female rats, Wistar breed, with induced endometriosis, were divided into four groups and underwent treatment for 28 days. The CTRL group received 0.5 mL/day of the vehicle; the DG group received 1 mg/kg b.w./day dienogest; the RiDG group received 0.25 mL/kg b.w./day RiDE and the D+RiDG group received 1 mg/kg b.w./day dienogest and 0.25 mL/kg b.w./day RiDE, respectively. Rats' weight, endometriotic lesion diameter and grade, and plasma levels of MMP-2, MMP-9, and TGF-β1 were assessed before and after treatment. The administration of RiDE in association with dienogest vs. dienogest determined a lower weight gain and a reduction in diameter of the endometriotic lesions. RiDE administration restored MMP2 and MMP9 plasma levels to initial conditions. Rubus idaeus extract may help in reducing dienogest-associated weight gain, lower the size of endometriotic lesions, and have anti-inflammatory effects through MMP2 and MMP9 reduction. [ABSTRACT FROM AUTHOR]

Endometriosis is a benign disease, which is also regarded as a precursor to ovarian malignancy. Dienogest is a progestin treatment for endometriosis with efficacy and tolerability. A 35-year-old Taiwanese lady with ovarian endometrioma had taken dienogest for the last 5 years. During sonographic follow-up, surgery was suggested owing to suspicious of malignant transformation of ovarian endometrioma. While she hesitated and turned to receive two cycles of oocyte retrieval because of nulliparity. Meanwhile, more papillary growth in the ovarian endometrioma with intratumor flow was found during follow-up. Laparoscopic enucleation was performed later, and pathology revealed clear cell carcinoma with peritoneal involvement, at least FIGO stage IIB. She then underwent debulking surgery to grossly no residual tumor and received adjuvant chemotherapy with no tumor recurrence in post-operative 17-months follow-up. Considering fertility preservation, conservative treatment of ovarian endometrioma is typically indicated for those women who have not yet completed childbearing. However, malignant transformation may still occur despite long-term progestin treatment. Therefore, careful image follow-up is still indispensable. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Medical management of adenomyosis is an emerging perspective in modern gynecology. Though levonorgestrel intrauterine system (LNG-IUS) and dienogest (DNG) effectively relieve symptoms in adenomyosis, neither has been approved for the same indication. Our study aims to compare the efficacy and safety of these progestins in treating adenomyosis. Objective: To study the efficacy and safety of LNG-IUS versus DNG in patients with symptomatic adenomyosis. Design: Open-labeled, parallel, single-centered, randomized clinical trial. Methods: Patients with adenomyosis-associated pain with or without abnormal uterine bleeding were randomly allocated to either LNG-IUS group or DNG group. The primary outcome was a reduction in painful symptoms after 12 weeks of treatment measured by visual analog scale (VAS) score. Changes in menstrual blood loss (MBL), improvement in quality of life (QoL), and adverse drug reactions were also analyzed. Results: The VAS score significantly decreased from baseline in both groups. The baseline and post-treatment VAS scores in the LNG-IUS group were 6.41 ± 1.07 and 3.41 ± 1.04 (p = <0.001) and in the DNG group, were 6.41 ± 0.95 and 3.12 ± 1.40 (p = <0.001), respectively. A significantly greater proportion of patients in the LNG-IUS group experienced lighter MBL as compared to the DNG group [27/30 (90%) in the LNG-IUS group versus 17/22 (77.2%) in the DNG group (p = 0.006)]. Both the groups had improvement in QOL scores calculated by the World Heath Organisation QOL scale (WHOQOL BREF) questionnaire; however, it was more pronounced in the DNG group [(28.76 ± 30.47 in the LNG-IUS group versus 48.26 ± 44.91 in the DNG group (p = 0.04)]. Both the agents were safe as there were no reported major adverse drug reactions. Conclusion: DNG can be an effective and safe alternative to LNG-IUS for the medical management of adenomyosis. Trial registration: The trial was prospectively registered at the clinical trial registry – India (CTRI) vide CTRI number CTRI/2020/05/025186. Plain language summary: Comparison of effectiveness and safety of Mirena (LNG-IUS) with dienogest for treatment of adenomyosis Adenomyosis is a condition affecting women, typically aged 40–50, but its incidence is rising in younger women, impacting fertility. It causes painful symptoms like dysmenorrhea, dyspareunia, chronic pelvic pain, and heavy menstrual bleeding. Managing symptoms is crucial, and medical approaches include levonorgestrel intrauterine system (LNG-IUS) and dienogest (DNG). LNG-IUS is reversible contraception, approved for eight years, effectively treating symptoms. DNG, a newer progestin, is effective for endometriosis, but evidence for adenomyosis is limited. This single-center, open-label randomized clinical trial compared LNG-IUS and DNG in treating adenomyosis. Women over 20 with pelvic pain were diagnosed using ultrasound and met specific criteria. After informed consent, participants were assigned randomly to LNG-IUS or DNG groups. Treatment outcomes, including pelvic pain, quality of life (QoL), and adverse effects, were assessed over 12 weeks. Out of 84 assessed, 74 women were recruited, with 34 in each group analyzed. After 12 weeks, both groups showed significantly reduced pelvic pain (VAS scores), but no significant difference was found between the groups. LNG-IUS resulted in a significantly greater reduction in heavy menstrual bleeding (HMB), whereas DNG showed better improvement in overall QOL. Adverse effects were similar in both groups, with hot flushes reported in the DNG group. This study is one of the few comparing LNG-IUS and DNG for adenomyosis, finding both effective for symptom relief. Although LNG-IUS was superior in reducing HMB, DNG showed better overall improvement in QoL. Safety profiles were similar. Previous studies support the efficacy of DNG in reducing adenomyosis symptoms. To conclude, both LNG-IUS and DNG effectively alleviate adenomyosis symptoms, with LNG-IUS superior in reducing heavy menstrual bleeding and DNG showing better overall improvement in QOL. DNG is a viable and effective alternative to LNG-IUS. [ABSTRACT FROM AUTHOR]

Background: Deep endometriosis represents a chronic, progressive disease, frequently characterized by pelvic pain and infertility. Although laparoscopic surgery is the mainstay of treatment for severe endometriosis-associated pain or failed medical therapy, post-surgical management of the disease still remains a subject of discussion. As for infertility treatment, the effectiveness of surgical intervention remains controversial due to the lack of robust trials. Few existing studies suggest that the use of selective progestin-dienogest may have a positive effect on improving endometriosis-associated pain, fertility rate and in-vitro outcomes. A possible improvement in the prognosis may be attributed to the positive effect of dienogest on the eutopic endometrium, which is structurally altered in endometriosis. Therefore, it has become reasonable to include hormonal therapy for the effective management of endometriosis after surgical intervention. Aim: We aimed to observe the available literature data to weigh prospects of combined surgical and medical therapy for more effective management of endometriosis. To bring more insights into better understanding the challenges associated with endometriosis treatment, epidemiology, classification systems, pathogenesis along with current treatment options were reviewed. Methods: For this purpose, the following electronic databases were searched: PubMed, Medline, Scopus, Cochrane Library, Web of Science, WES, Science Direct, NCBI, National Library of Medicine, Springer. Results: Overall, 120 articles, expert recommendations and practice committee options were reviewed, 59 of them displayed certain degree of statistical significance. They were analyzed and discussed in our article. Conclusion: After literature review, it has become more obvious that existing research data are mostly heterogeneous and inconclusive; therefore, the majority of study findings can't be generalized. Research data is limited to accurately analyze and determine the timing and duration of optimal hormonal therapy after surgery for deep endometriosis. Further studies are needed to address the challenges of effective management of endometriosis. [ABSTRACT FROM AUTHOR]

Endometriosis is a common gynecological condition with a complex physio-pathological background. This study aimed to assess the role of Rubus idaeus leaf extract (RiDE) as a potential therapeutic agent in reducing the size of the endometriotic lesions and modulate the plasma expression of MMP-2, MMP-9, and TGF-β1. The endometriotic lesions were induced in a rat model by the autologous transplant of endometrium. Thirty-six female rats, Wistar breed, with induced endometriosis, were divided into four groups and underwent treatment for 28 days. The CTRL group received 0.5 mL/day of the vehicle; the DG group received 1 mg/kg b.w./day dienogest; the RiDG group received 0.25 mL/kg b.w./day RiDE and the D+RiDG group received 1 mg/kg b.w./day dienogest and 0.25 mL/kg b.w./day RiDE, respectively. Rats’ weight, endometriotic lesion diameter and grade, and plasma levels of MMP-2, MMP-9, and TGF-β1 were assessed before and after treatment. The administration of RiDE in association with dienogest vs. dienogest determined a lower weight gain and a reduction in diameter of the endometriotic lesions. RiDE administration restored MMP2 and MMP9 plasma levels to initial conditions. Rubus idaeus extract may help in reducing dienogest-associated weight gain, lower the size of endometriotic lesions, and have anti-inflammatory effects through MMP2 and MMP9 reduction.

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 cm 3 , 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., Competing Interests: Conflict of interest The authors reported no conflict of interest, (Copyright © 2024. Published by Elsevier Masson SAS.)

To evaluate the intraoperative visual effect of treatment with GnRH-analogues and Dienogest in endometriosis. Retrospective observational study. 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. 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. 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. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Currently, the use of dienogest in clinical practice has increased significantly, and many studies have focused on its effectiveness and safety in the treatment of endometriosis and adenomyosis; however, the effects of treatment with dienogest on uterine fibroid size in patients with endometriosis or adenomyosis have not been investigated., Aim: To explore changes in fibroid size in patients with concomitant uterine fibroids undergoing dienogest treatment for endometriosis or adenomyosis and to evaluate the effectiveness and safety of the drug., Methods: The clinical data of patients with uterine fibroids treated with dienogest for endometriosis or adenomyosis at Peking University First Hospital from January 2021 to January 2023 were retrospectively analyzed., Results: The maximum uterine fibroid diameter and volume increased after 3 months, 6 months and 1 year of dienogest treatment compared with those before treatment ( P < 0.01). The maximum diameter and volume of the uterine adenomyoma increased after 3 months of dienogest treatment but decreased after 6 months and 1 year of treatment compared with those before treatment, but the difference was not significant ( P > 0.05). Endometrial thickness and antigen 125 levels were significantly thinner and decreased, respectively, after dienogest treatment ( P < 0.01). Pearson's correlation analysis revealed that the increase in uterine fibroid volume after 3 months of dienogest treatment was positively correlated with the basic uterine fibroid volume ( r = 0.792, P < 0.01). Among 64 patients with dysmenorrhea, 63 experienced significant relief of dysmenorrhea after 6 months of treatment with dienogest, and all patients experienced significant relief of dysmenorrhea after 12 months. Patients were able to tolerate the drugs, with an average drug tolerance score of 8.73., Conclusion: The use of dienogest in patients with endometriosis or adenomyosis combined with uterine fibroids can effectively relieve the patient's pain symptoms and significantly reduce the sizes of ovarian endometriotic cysts, but it cannot inhibit uterine fibroid growth., Competing Interests: Conflict-of-interest statement: All authors declare that they have no conflict of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Adenomyosis is a chronic disease associated with abnormal uterine bleeding and debilitating pain with severely reduced quality of life in many affected women. Primary strategies for its management encompass surgical interventions, hormonal therapy, or a synergistic blend of these therapeutic modalities. Dienogest (DNG), a new progestin, is primarily utilized to treat adenomyosis due to its exceptional selectivity for the progesterone receptor. In this uncommon case report, we introduce a 42-year-old woman who experienced hemorrhagic shock as a result of uterine bleeding and pulmonary embolism that occurred while a patient was undergoing dienogest therapy for uterine adenomyosis. This situation necessitated blood transfusion and introduction of drugs then an emergency hysterectomy was scheduled followed by the initiation of anticoagulation. We hypothesize that the emergence of pulmonary embolism was intimately tied to adenomyosis, and the occurrence of hemorrhagic shock was likely due to the intake of dienogest., (© 2024 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

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., Competing Interests: Conflict of interest The authors have no conflicts of interest relevant to this article., (Copyright © 2024. Published by Elsevier B.V.)

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., Competing Interests: Declaration of Competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Although endometriosis is a benign disease, it is associated with cancer-related gene mutations, such as KRAS or PIK3CA . Endometriosis is associated with elevated levels of inflammatory factors that cause severe pain. In a previous study, we demonstrated that KRAS or PIK3CA mutations are associated with the activation of cell proliferation, migration, and invasion in a patient-derived immortalized endometriotic cell line, HMOsisEC10. In this study, we investigated the effects of these mutations on progesterone resistance. Since the HMOsisEC10 had suppressed progesterone receptor (PR) expression, we transduced PR-B to HMOsisEc10 cell lines including KRAS mutant and PIK3CA mutant cell lines. We conducted a migration assay, invasion assay, and MTT assay using dienogest and medroxyprogestrone acetate. All cell lines showed progesterone sensitivity with or without mutations. Regarding inflammatory factors, real-time quantitative RT-PCR revealed that the KRAS mutation cell line exhibited no suppression of Cox-2 and mPGES-1 on progesterone treatment, whereas IL-6, MCP-1, VEGF, and CYP19A1 were significantly suppressed by progesterone in both mutated cell lines. Our results suggest that KRAS mutation and PIK3CA mutation in endometriotic cells may not be associated with progesterone resistance in terms of aggressiveness. However, KRAS mutations may be associated with progesterone resistance in the context of pain.

Ovarian endometrioma (OE) is a common gynecological disease that is often treated with surgery and hormonal treatment. However, ovarian cystectomy can impair the ovarian reserve (OR). Previously, we showed that perioperative administration of dienogest (DNG) is an effective option for OR preservation. However, there were differences in the extent of OR preservation among patients following perioperative DNG treatment. In the current study, we performed a global examination of serum microRNAs (miRNAs) to identify accurate biomarkers that predict post-operative restoration of OR following perioperative DNG treatment. We also sought to identify specific miRNAs related to the anti-Müllerian hormone (AMH). miRNA sequencing was performed on serum samples obtained from twenty-seven patients who received perioperative DNG treatment. Candidate miRNAs were selected by comparing patients whose ORs were restored postoperatively (responder group, n = 7) with those whose ORs were not (non-responder group, n = 7). miR-370-3p and miR-1307-3p were significantly upregulated in the responder group, whereas miR-27b-3p was upregulated in the non-responder group. The pretreatment value of each miRNA could predict DNG responsiveness for OR following ovarian cystectomy (area under the curve [AUC] > 0.8). The quantitative polymerase chain reaction (qPCR) revealed only miR-1307-3p was found to be significantly upregulated in the responder group (P < 0.05). In addition, we identified miR-139-3p, miR-140-3p, and miR-629-5p as AMH-associated miRNAs. The transition of AMH showed a correlation with miR-139-3p (P < 0.05, r = -0.76). The miRNAs identified herein represent potential serum biomarkers of clinical value in predicting OR prior to DNG treatment., Competing Interests: Declaration of Competing Interest The authors have declared that no conflicts of interest exist., (Copyright © 2023. Published by Elsevier B.V.)

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.