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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]

Background: Ovarian endometriosis cysts (OEC) are common chronic diseases occurring in women of reproductive age. Hormone therapy, including the use of oral contraceptives (COCs) and progestins, is widely employed in the treatment of endometriosis and OEC. Objective: This study aims to compare therapeutic effects of long-term daily use of dienogest (DNG, 2 mg) versus drospirenone (DRSP, 3 mg)/ethinyl estradiol (EE, 20 μg) daily on ovarian endometrial cysts, particularly focusing on cysts suppression. Methods: A retrospective analysis was conducted on 84 patients diagnosed with OEC, with 42 receiving DNG and 42 treated with DRSP/EE. After 6 months, assessments were made regarding pain symptoms, size of OEC, tumor markers, and adverse reactions. Results: After 6 months of treatment, both DNG and DRSP/EE effectively alleviated pain in patients with ovarian endometriotic cysts. DNG demonstrated more significant improvements than DRSP/EE in reducing tumor size, mainly in terms of higher drug efficacy and greater percentage of tumor shrinkage. However, DRSP/EE significantly reduced the expression of the tumor markers CA125 and CA199 in our study. Patients taking DNG had a higher likelihood of experiencing side effects than those on DRSP/EE, mainly vaginal bleeding and irregular menstrual periods. Conclusions: Both DNG and DRSP/EE are effective in treating ovarian endometrial cysts. DNG appears to be superior in terms of tumor reduction, while DRSP/EE more significantly decreases the expression of the tumor markers and has fewer side effects. [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]

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]

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]

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]

Endometriosis is characterized by the implantation of endometrial cells outside the uterus. This hormone-dependent disease is highly prevalent among women of reproductive age. Clinical symptoms of endometriosis include dysmenorrhea, pelvic pain, and infertility, which can negatively impact the overall quality of life of those affected. The medical treatment of endometriosis serves as an important therapeutic option, aimed at alleviating pain associated with the condition and suppressing the growth of endometriotic lesions. As such, it is employed as an adjuvant therapy following surgery or an empirical treatment after the clinical diagnosis of endometriosis. Dienogest, a fourth-generation progestin, has received approval for the treatment of endometriosis in many countries. A growing body of evidence has demonstrated its efficacy in managing endometriosis-associated pain, preventing symptoms, and reducing lesion recurrence. In this review, we examine the clinical efficacy, safety, and tolerability of dienogest in treating endometriosis. We also provide updated findings, drawing from clinical studies that focus on the long-term use of this medication in patients with endometriosis. [ABSTRACT FROM AUTHOR]

A comparative analysis of the cytostatic effects of progestins (gestobutanoyl, megestrol acetate, amol, dienogest, and medroxyprogesterone acetate), glucocorticoids (hydrocortisone, dexamethasone), and diclofenac on tumor cells was carried out in order to confirm their in silico predicted probabilities experimentally. The results showed the different sensitivity of HeLa, MCF-7, Hep-2, K-562, and Wi-38 cell lines to progestins, glucocorticoids, and diclofenac. The minimum IC50 was found for progestin gestobutanoyl (GB) as 18 µM for HeLa cells, and varied from 31 to 38 µM for MCF-7, Hep-2, and K-562. Glucocorticoids and diclofenac were much less cytotoxic in the HeLa, MCF-7, and Hep-2 cell lines than progestins, with IC50 values in the range of 150–3000 μM. Myelogenous leukemia K-562 cells were the least sensitive to the action of progestins and glucocorticoids but the most sensitive to diclofenac, which showed a pronounced cytotoxic effect with an IC50 of 31 μM. As we have shown earlier, progestins can uniquely modulate MPTP opening via the binding of adenine nucleotide translocase. On this basis, we evaluated the expression of adenylate nucleotide translocase ANT1 (SLC25 A4) as a possible participant in cytotoxic action in these cell lines after 48 h incubation with drugs. The results showed that progestins differently regulated ANT1 expression in different cell lines. Gestobutanoyl had the opposite effect on ANT1 expression in the HeLa, K562, and Wi-38 cells compared with the other progestins. It increased the ANT1 expression more than twofold in the HeLa and K562 cells but had no influence on the Wi-38 cells. Glucocorticoids and diclofenac increased ANT1 expression in the Wi-38 cells and decreased it in the K562, MCF-7, and Hep-2 cells. The modulation of ANT1 expression discovered in our study can be a new explanation of the cytotoxic and cytoprotective effects of hormones, which can vary depending on the cell type. ANT isoforms in normal and cancerous cells could be a new target for steroid hormone and anti-inflammatory drug action. [ABSTRACT FROM AUTHOR]

Background and objective: We aimed to identify the effects of dienogest on inducing thromboembolism in rats following exposure to dienogest for a period of either 10 days (2 estrus cycles), 20 days (4 estrous cycles), or 30 days (6 estrus cycles). Materials and Methods: To do so, 40 rats were divided into 4 groups; dienogest-free control group, dienogest treated for 10 days (G1), 20 days (G2), and 30 days (G3). Then lungs and femoral veins were collected from subjects after sacrificing them, and these tissues were fixed for histological analysis. Results: Results showed that venous thromboembolism increased with dienogest therapy as indicated by the increased score of inflammation in the lung tissues, alongside increased thickness of femoral vein wall, and histological findings of fibrin deposition, vessel congestion, inflammatory cells infiltrations, and epithelial desquamation. Conclusion: To sum up, dienogest long-term therapy could be a risk for cardiac thrombotic diseases, and therefore we do advise using alternative progesterone or adding estrogen in low doses to minimize toxic effects primarily when used as postmenopausal replacement therapy. [ABSTRACT FROM AUTHOR]

The objective of this study is to determine whether dienogest therapy after endometriosis surgery reduces the risk of recurrence compared with placebo or alternative treatments (GnRH agonist, other progestins, and estro-progestins). The design used in this study is systematic review with meta-analysis. The data source includes PubMed and EMBASE searched up to March 2022. A systematic review and meta-analysis were performed in accordance with guidelines from the Cochrane Collaboration. Keywords such as "dienogest," "endometriosis surgery," "endometriosis treatment," and "endometriosis medical therapy" were used to identify relevant studies. The primary outcome was recurrence of endometriosis after surgery. The secondary outcome was pain recurrence. An additional analysis focused on comparing side effects between groups. Nine studies were eligible, including a total of 1668 patients. At primary analysis, dienogest significantly reduced the rate of cyst recurrence compared with placebo (p < 0.0001). In 191 patients, the rate of cyst recurrence comparing dienogest vs GnRHa was evaluated, but no statistically significant difference was reported. In the secondary analysis, a trend toward reduction of pain at 6 months was reported in patients treated with dienogest over placebo, with each study reporting a significantly higher reduction of pain after dienogest treatment. In terms of side effects, dienogest treatment compared with GnRHa significantly increased the rate of spotting (p = 0.0007) and weight gain (p = 0.03), but it was associated with a lower rate of hot flashes (p = 0.0006) and a trend to lower incidence of vaginal dryness. Dienogest is superior to placebo and similar to GnRHa in decreasing rate of recurrence after endometriosis surgery. A significantly higher reduction of pain after dienogest compared with placebo was reported in two separate studies, whereas a trend toward reduction of pain at 6 months was evident at meta-analysis. Dienogest treatment compared with GnRHa was associated with a lower rate of hot flashes and a trend to lower incidence of vaginal dryness. [ABSTRACT FROM AUTHOR]

Objectives: To compare the effectiveness of dienogest (DIE) and norethisterone acetate (NETA) regimens in the treatment of endometrial hyperplasia (EH) without atypia. Methods: Participants were premenopausal women with irregular uterine bleeding, and endometrial hyperplasia without atypia on endometrial biopsy. Enrolled patients were randomly allocated into two groups: group I got DIE 2 mg/day (orally Visanne) for 14 days (10th to the 25th day of cycle) while group II received between the 16th and 25th day of the cycle, norethisterone acetate (NETA) 15 mg/d (orally Primolut Nor) was administered for 10 days. Both groups continued the therapy for six months. Results: The DIE group showed a higher resolution (32.7%) and regression (57.7%) than NETA group (31% & 37.9%, respectively) with significant regression (p = 0.039). No progression in DIE group while four (6.9%) women in NETA group were recorded a progression to complex type without a significance. Also, NETA group showed a significant persistence rate (22.5%) than DIE group (3.8%) (p = 0.005). Also number in NETA group managed by hysterectomy with significant difference (p = 0.042). Conclusion: If used as first-line treatment, Dienogest produces a better rate of regression and a lower incidence of hysterectomy than Norethisterone Acetate does when used in EH without atypia. [ABSTRACT FROM AUTHOR]

Background: To comprehensively evaluate the influence of dienogest (DNG) versus non-DNG pretreatment on in vitro fertilization and embryo transfer (IVF-ET) outcomes for patients with endometriosis. Methods: PubMed, Embase, Cochrane Library, Web of Science, CNKI, WanFang, and VIP were comprehensively searched for relevant publications until September 14, 2022. Primary outcomes included clinical pregnancy rate and live birth rate. Secondary outcomes included retrieved oocytes, mature oocytes, blastocysts, growing follicles, transferrable embryos, fertilization rate, implantation rate, and miscarriage rate. Subgroup analysis was performed according to different grouping methods and embryo types. Results: Five studies of 568 females with endometriosis were involved in this systematic review and meta-analysis. DNG treatment exhibited similar effects to non-DNG treatment on either the primary or the secondary outcomes (all P > 0.05). The DNG group had a significantly greater clinical pregnancy rate than the non-hormonal treatment group (pooled relative risk [RR]: 2.055, 95% confidence interval [CI]: 1.275, 3.312, P = 0.003), and exhibited a significantly lower clinical pregnancy rate than the long gonadotropin-releasing hormone agonist (GnRH-a) group (RR: 0.542, 95%CI: 0.321, 0.916, P = 0.022). For patients undergoing fresh embryo transfer, the DNG group displayed a significantly greater clinical pregnancy rate versus the non-DNG group (pooled RR: 1.848, 95%CI: 1.234, 2.767, P = 0.003). Patients receiving DNG had a significantly greater live birth rate than those with non-hormonal treatment (pooled RR: 2.136, 95%CI: 1.223, 3.734, P = 0.008), while having a significantly lower live birth rate than the long GnRH-a group (RR: 0.441, 95%CI: 0.214, 0.907, P = 0.026). While using fresh embryos, patients with DNG treatment had an increased live birth rate, compared with those without DNG treatment (pooled RR: 2.132, 95%CI: 1.090, 4.169, P = 0.027). Conclusion: DNG treatment may have similar effects to non-DNG treatment on IVF-ET outcomes. The clinical pregnancy rate and live birth rate after DNG treatment may be significantly higher than those after non-hormonal treatment. More evidence is warranted to corroborate these findings. [ABSTRACT FROM AUTHOR]

Endometriomas (chocolate cysts) are cystic lesions that can develop on ovaries, and are characterized by the presence of ectopic endometrial tissue or similar tissue. Such lesions can cause a decline in the number and quality of oocytes, and lead to implantation failure. In this study, we retrospectively assessed the efficacy of repeated endometrioma aspiration and dienogest combination therapy in patients suffering endometriosis-associated infertility with endometriomas. A comparison was made between a treated group that underwent combination therapy followed by controlled ovarian hyperstimulation (COH) (n = 30) and a control group that did not undergo treatment (n = 40), at the IVF Osaka Clinic from September 2019 to September 2021. There were no differences in patient background between the two groups. A reduction in endometrioma size continued for 12 months after treatment. The numbers of follicles that developed to 15 mm or greater in size following COH and mature oocytes were significantly lower in the treated group compared to those in the control group. The levels of inflammatory cytokines in the follicular fluid significantly decreased in the treated group (p < 0.05). In patients in the treated group who underwent a second ova retrieval, the results were compared between those in the first ova retrieval (immediately after the end of treatment) and those in the second ova retrieval (four months after the first retrieval). The numbers of follicles following COH, retrieved, mature and fertilized ova were significantly increased in the second ova retrieval. [ABSTRACT FROM AUTHOR]

Endometriosis affects up to 10% of women of reproductive age, causing dysmenorrhea, chronic pelvic pain, and infertility. The current key drug for endometriosis is dienogest, a progestin with high specificity for the progesterone receptor. To reveal the direct anti-endometriotic effect of dienogest on ovarian endometriotic cells, we investigated the genome-wide gene expression profiles of ovarian endometriotic stromal cells with (Dienogest group) or without dienogest treatment (Control group) and compared the groups' gene expression profiles. We performed a gene ontology (GO) analysis and Ingenuity pathway analysis using these data. To validate the microarray data, we performed real-time RT-PCRs and immunohistochemistry for the differentially expressed genes between the two groups. Of 647 genes differentially expressed between the two groups, 314 genes were upregulated and 333 were downregulated in the Dienogest group versus the Control group. The GO analysis showed that the regulation of macrophage chemotaxis, the collagen catabolic process, and the proteoglycan biosynthetic process are the main biological processes closely associated with the differentially expressed genes. We identified 20 canonical pathways that were most significantly differentially expressed in the Dienogest group versus the Control group. We observed that matrix metalloproteinases (MMPs) are the genes in these pathways that are most closely associated with dienogest treatment. Of components involved in the regulation of macrophage chemotaxis, colony-stimulating factor 1 and macrophage-stimulating 1 are potential upstream regulators of MMPs and were observed herein to be suppressed by dienogest. Our results suggest that dienogest may thus exert its anti-endometriotic effect by directly suppressing MMPs. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to compare the effects of Dienogest and medroxyprogesterone acetate (MPA) on the recurrence of endometriosis lesions and clinical symptoms in women undergoing laparoscopic surgery. Methods: This single center clinical trial was conducted among 106 women with endometriosis undergoing laparoscopic surgery who candidate receiving post-surgery hormone therapy. Participants were allocated to two groups. The first group received Dienogest pills (2 mg) daily for the first three months and then cyclic for three months afterward. The second group received MPA pills twice daily (10 mg) for three months and then cyclic for the next three months. Six months after the intervention, the rate of endometriosis recurrence, the size of endometriosis lesions and pelvic pain were assess and compared between two groups. Results: Finally, data were evaluated based on 48 and 53 women in the Dienogest and MPA groups, respectively. After 6 months follow-up assessments the pelvic pain score was significantly lower in Dienogest group than MPA group (P < 0.001). There was not statistically difference between two groups in terms of recurrence rate of endometriosis (P = 0.4). Although the size of endometriosis cyst recurrence was smaller in Dienogest group compared to MPA group (P = 0.02). Conclusions: The findings showed that Dienogest treatment has better effect in reducing pelvic pain and the mean size of the recurrent endometriosis lesions after endometriosis laparoscopic surgery when compared to MPA treatment. Although the recurrent rate of endometriosis was similar between these treatments. [ABSTRACT FROM AUTHOR]

Objective: To investigate the safety and efficacy of adjuvant gonadotropin‐releasing hormone agonist (GnRH‐a) treatment followed by maintenance dienogest (DNG) therapy after uterus‐sparing surgery. Methods: Retrospective cohort study. A total of 190 patients with severe adenomyosis underwent uterus‐sparing surgery between January 2010 and June 2020. Of these patients, 90 were analyzed. Forty‐six patients (control group) received adjuvant 6‐month GnRH‐a therapy alone after uterus‐sparing surgery, and 44 patients (maintenance group) received postoperative 6‐month GnRH‐a treatment followed by maintenance DNG therapy (2 mg/day orally). The median follow‐up period was 18 months. The study was analyzed using generalized estimating equations. Results: At baseline, the characteristics of patients in each group were comparable. Compared with the control group, the maintenance group had a significant improvement in the visual analog scale score of dysmenorrhea (P < 0.001), hemoglobin level (P = 0.004), and uterine volume (P = 0.004) from baseline to 18 months after uterus‐sparing surgery. The symptom recurrence rate was significantly lower in the maintenance group than in the control group (4.6% vs. 37.0%, P < 0.001). Conclusions: The findings of this study suggest that combinatorial treatment with GnRH‐a (adjuvant treatment) and DNG (maintenance therapy) represents a safe and effective short‐term therapy after uterus‐sparing surgery for adenomyosis. Synopsis: Maintenance DNG therapy following adjuvant GnRH‐a treatment after uterus‐sparing surgery was identified as an effective therapy for symptom control and prevention of recurrent adenomyosis. [ABSTRACT FROM AUTHOR]

Introduction: Dienogest (DNG) was demonstrated to be comparable to gonadotropin-releasing hormone agonist (GnRH-a) in controlling symptoms of endometriosis. GnRH-a is used before in vitro fertilization (IVF) in women with endometriosis to improve pregnancy outcomes. We aimed to determine the effect of DNG pretreatment on IVF outcomes, including number of mature oocytes, rate of clinical pregnancies, and rate of live births in women with endometriosis. Methods: All studies involving DNG, IVF, and endometriosis were searched from the PubMed; Ovid/MEDLINE, Wanfang, CQVIP, China National Knowledge Infrastructure databases; and ClinicalTrials.gov. The study population was women with endometriosis in IVF. Randomized controlled trials and cohort studies were included. All included studies comprised a DNG group and a control group. The outcomes were number of mature oocytes, rate of clinical pregnancies, and rate of live births. We calculated the odds ratio or mean difference and 95% confidence interval for each study and used a random-effects model to estimate the results. Results: Five articles were screened by the search strategy. One article without a control group was excluded. Finally, four articles with 422 patients were included. No significant differences in number of mature oocytes (MD = −1.27, 95% CI: −3.63 to 1.09, I2 = 91%), the rate of clinical pregnancies (odds ratio = 1.07, 95% CI: 0.33–3.47, I2 = 84%), or the rate of live births (odds ratio = 1.09, 95% CI: 0.34–3.46, I2 = 84%) were found between the DNG group and the control group. Conclusion: Pretreatment with DNG for women with endometriosis who underwent IVF could not improve the number of mature oocytes, the rate of clinical pregnancies, or the rate of live births. [ABSTRACT FROM AUTHOR]

The medical management of painful endometriosis is essentially based on anti-gonadotropic molecules and analgesics in the absence of a desire for pregnancy on the part of the patients, and constitutes the first therapeutic step. Dienogest, a recent treatment, has found its place in the management algorithm for painful endometriosis in view of its proven efficacy. It is recommended as a second-line treatment. The ANSM has very recently (March 2023) issued recommendations aimed at controlling the risk of meningioma for various progestogens including dienogest. Relugolix Combination Therapy, which combines a GnRH antagonist and an estrogen-progestin addback therapy in a single tablet, appears to be a promising treatment for painful endometriosis and the initial data on the safety of the treatment (after 6 months of use) are reassuring. Today, anti-aromatases, SERMs or selective inhibitors cannot be considered as an alternative therapy in the medical treatment of painful endometriosis. [ABSTRACT FROM AUTHOR]

Dienogest is effective in reducing endometriosis‐related pain symptoms. This study aims to investigate and compare the pharmacokinetic profiles and safety of test formulations to reference formulations of dienogest in healthy Chinese female volunteers under fasting or fed conditions. The purpose of this single‐center, randomized, open‐label, 2‐sequence, 2‐period crossover clinical trial was to evaluate the safety and pharmacokinetic profiles of the 2 formulations under fasting and fed conditions. Additionally, 48 healthy female volunteers were selected and divided at random into the fasting and the fed group. After dosing, the venous blood was collected through indwelling catheters. Dienogest plasma concentrations were measured using liquid chromatography–tandem mass spectrometry after the plasma samples were prepared with the protein precipitation method. Under either fasting or fed conditions, the pharmacokinetic parameters (maximum observed concentration, area under the concentration–time curve [AUC] from time 0 to the last measurable concentration, and AUC from time 0 to infinity) for dienogest between the test and reference products, geometric mean ratio, and 90%CI were all within the range of 80%–125%. The 2 dienogest products were bioequivalent. Based on maximum observed concentration and AUC from time 0 to the last measurable concentration, the generic dienogest was bioequivalent to the original dienogest in this study conducted under fasting and fed conditions in healthy Chinese women (study CTR20190063 on chinadrugtrials.org.cn registry). [ABSTRACT FROM AUTHOR]

Background: Diagnostic and treatment delays have caused significant impacts on the physical and emotional well-being of adolescents with endometriosis, though such research is limited. This study aimed to assess the effects of one-year dienogest therapy on the clinical picture, pain patterns, psycho-emotional status, and quality-of-life indicators in adolescents with endometriosis after surgical treatment. Methods: The study enrolled 32 girls aged 13–17 with peritoneal endometriosis to analyze one-year dynamics of the Visual Analog Scale (VAS), McGill Pain Questionnaire, Beck Depression Scale (BDI), Hospital Anxiety and Depression Scale (HADS), Spielberger State-Trait Anxiety Inventory (STAI) and SF-36 quality-of-life survey scores along with clinical and laboratory indicators before surgery and after one-year dienogest therapy. Results. The therapy provided a significant alleviation of endometriosis-associated clinical symptoms, including dysmenorrhea, pelvic pain, gastrointestinal/dysuria symptoms, decreased everyday activity (<0.001), a decrease in anxiety/depression scores (BDI, HADS, STAI), and quality-of-life improvement (<0.001). These effects were accompanied by beneficial dynamics in hormone and inflammatory markers (prolactin, cortisol, testosterone, estradiol, CA-125, neutrophil/lymphocyte ratio; <0.005) within reference ranges. A low body mass index and high C-reactive protein levels were associated with higher VAS scores; a high estradiol level was a factor for anxiety/depression aggravation (<0.05). Conclusions: Dienogest, after surgical treatment, significantly improved quality of life and reduced pain symptoms while showing good tolerability and compliance, and reasoning with timely hormonal therapy in adolescents with endometriosis. [ABSTRACT FROM AUTHOR]

Background: Adenomyosis is an estrogen-dependent gynecologic condition that can cause pain symptoms, heavy menstrual bleeding, and infertility. Several treatments, including hormonal therapy, can improve patients' quality of life through alleviating symptoms. Dienogest (DNG), a 19-norsteroid derivative oral progestin, is a promising treatment option for adenomyosis. Objectives: This review aims to summarize the clinical outcomes (efficacy and adverse events) of DNG treatment for symptomatic adenomyosis compared with other hormonal treatments, discuss the mechanism underlying adverse events, and identify future challenges. Methods: A literature search was performed across the PubMed and Google Scholar databases up to March 2022 to identify relevant literature. Outcome: Out of 449 identified records, 37 articles met the inclusion and exclusion criteria. Five prospective and three retrospective studies showed that DNG and other hormonal agents had similar efficacy for pain relief; however, the most common adverse event of DNG was abnormal uterine bleeding. Specific demographic and clinicopathologic characteristics have been identified as associated with an increased risk of bleeding. Several factors, such as diffuse or type 1 adenomyosis, advanced reproductive age, severe dysmenorrhea, elevated serum CA125 levels, or low hemoglobin levels, may be implicated in bleeding risk; however, there is no accurate and reliable parameter. Future challenges with the widespread use of DNG include validation of candidate risk indicators and approaches to treat diffuse or type 1 adenomyosis. Conclusions and Outlook: DNG represents an important therapeutic option to be included in the treatment algorithm for adenomyosis owing to sufficient pain relief, despite high rates of bleeding-related adverse events. Clinicians should consider an individual's potential risk factors for bleeding until high-quality evidence is available. [ABSTRACT FROM AUTHOR]

Endometriosis-related conditions such as subcutaneous endometriosis have been frequently seen in recent years, and dienogest or surgical excision is generally preferred as a treatment option. Our aim in this study is to determine which treatment option will be more effective in reducing the symptoms of patients with cesarean scar endometriosis. Study design This prospective study was performed with 21 patients diagnosed with cesarean scar endometriosis. The demographic features of the patients, lesion sizes before and after medical and surgical treatment, VAS scores and Ca-125 levels were recorded. VAS scores and lesion sizes were compared before-after medical treatment and before-after surgery in same group. A total of 18 women were identified, with a mean age of 32.3 ± 5.7 years. No significant decrease in lesion size was observed in the 1st and 6th-month controls after the use of dienogest (p > 0,05), while a significant decrease in VAS scores was detected (p < 0,05). After surgery, the decrease in both lesion size and VAS scores was found statistically significant (p < 0,05). Dienogest, which is frequently used in the medical treatment of pelvic and ovarian endometriosis, reduces pain minimally in cesarean scar endometriosis but does not provide a change in lesion size. Therefore, surgical treatment of cesarean scar endometriosis seems to be more effective in reducing pain and decreasing the size of the lesions. [ABSTRACT FROM AUTHOR]

Synopsis: Dienogest appears not to have any adverse breast effects on women of reproductive age. [ABSTRACT FROM AUTHOR]

Objective: To compare the efficacy of dienogest and GnRH-a after endometriosis surgery. Methods: Patients with endometriosis who were admitted to our hospital from December 2020 to March 2022 were randomly collected. A total of 81 patients were collected and divided into 40 cases in the control group and 41 cases in the observation group. Among them, the control group was treated with GnRH-a drug, and the observation group was treated with dienogest (DNG). Results: The study found that the therapeutic effects of the two drugs were basically the same in patients with endometriosis. The VAS and Kupperman scores of the control group were 0.78 ± 0.8, 3.9 ± 1.84, P < 0.05, respectively; the VAS and Kupperman scores of the observation group were 0.73 ± 0.78, 1.55, respectively ± 1.24, P < 0.05, the difference was statistically significant.In the case of postoperative recurrence, the observation group was better than the control group, with 8 cases of recurrence in the control group and 2 cases of recurrence in the observation group, P < 0.05. Conclusion: In the comparison of postoperative efficacy of the two drugs on patients with endometriosis, dienogest is better than GnRH-a adjuvant drug in postoperative recurrence, and has a good improvement and application, which is worthy of further promotion in clinical practice. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to investigate whether serum leucine‐rich α2‐glycoprotein (LRG) is a useful diagnostic biomarker for endometriosis, including the evaluation of treatment efficacy and exploration of LRG production in endometriotic lesions. Methods: Forty‐three women with endometriomas were compared to 22 women with benign ovarian cysts and 30 women who underwent assisted reproduction as controls. Changes in serum LRG levels were assessed before and after surgery, and during dienogest treatment. LRG expression in endometriotic tissue samples was evaluated using immunoblotting. Results: Serum LRG levels in the endometrioma group (80.0 ± 36.3 μg/mL) were significantly higher than those in the benign ovarian cyst (65.1 ± 27.0 μg/mL, p = 0.0265) and control (57.8 ± 22.3 μg/mL, p = 0.0028) groups. Serum LRG levels after endometrioma surgery were significantly lower than preoperative levels (p = 0.0484). Serum LRG levels consistently decreased during dienogest treatment. LRG expression levels were significantly higher in endometriotic tissues than in the normal endometrium. Conclusion: Serum LRG, possibly derived from local and systemic origins, could be used as a potential biomarker for the diagnosis and treatment of endometriosis. Serum leucine‐rich a2‐glycoprotein (LRG) levels in the endometrioma group were significantly higher than those in the benign ovarian cyst and control groups. In addition, serum LRG levels decreased after the surgery and during the dienogest treatment. Therefore, serum LRG can be used as a potential biomarker for diagnosis and treatment response in endometriosis. [ABSTRACT FROM AUTHOR]

Cloacal exstrophy (CE) is a rare congenital disease that requires multiple surgeries for complex gastrointestinal and genitourinary anomalies. Long-term complications are not uncommon; however, they are poorly reported. Pyosalpinx is sometimes encountered during CE management in adolescents and young adults. A 28-year-old woman with a history of CE presented with fever, lower abdominal pain, and vomiting and was diagnosed with left pyosalpinx. Computed tomography-guided drainage and intravenous antibiotic administration were successful; however, she had 2 readmissions for recurrent pyosalpinx 1 week after discharge and again 4 months later. She was administered Dienogest, a synthetic progestin, to prevent recurrent pyosalpinx and had no recurrence for 8 months. Dienogest is a conservative treatment choice for preventing the recurrence of pyosalpinx for patients with CE. [ABSTRACT FROM AUTHOR]

We developed and validated a liquid chromatography high-resolution mass spectrometry method for the absolute quantification of 51 steroids for clinical analysis of human serum and, for the first time, peritoneal fluid. Data acquisition was performed in both targeted and untargeted mode simultaneously, thus allowing the accurate and precise quantification of the main components of the classical steroid pathways (17 steroids) as well as the analysis of 34 additional non-classical steroids. For targeted analysis, validation was performed according to FDA guidelines, resulting, among other parameters, in accuracy < 13% RSD and precision < 10% relative error, for both inter- and intra-day validation runs. By establishing steroid-specific response factors, the calibration curves of the targeted analytes can be extended to untargeted analytes. This approach opens novel possibilities for the post hoc analysis of clinical samples as the data can be examined for virtually any steroid even after data acquisition, enabling facile absolute quantification once a standard becomes available. We demonstrate the applicability of the approach to evaluate the differences in steroid content between peripheral serum and peritoneal fluid across the menstrual cycle phases, as well as the effect of the synthetic gestagen dienogest on the steroid metabolome. [ABSTRACT FROM AUTHOR]

Introduction: Contraceptives containing ethinylestradiol (EE) induce changes in the coagulation system and are associated with a risk of venous thromboembolism. However, studies comparing the effects of combined oral contraceptives containing EE and low-potency estrogens (ie, estradiol [E2 ] and estradiol valerate [EV]) on coagulation biomarkers are limited. This study represents secondary outcomes of a randomized trial comparing combined oral contraceptives containing EV + dienogest (DNG), EE + DNG, and DNG alone on selected coagulation biomarkers. We could compare the specific effects of the different estrogen components owing to the inclusion of preparations containing the same progestin.Material and Methods: We enrolled 59 healthy, 18- to 35-year-old, non-smoking women, of whom three discontinued. The participants were randomly allocated to 9 weeks of continuous treatment with EV 2 mg + DNG 2-3 mg (n = 20), EE 0.03 mg + DNG 2 mg (n = 20), or DNG 2 mg (n = 19). Blood samples were collected at baseline and after 9 weeks. We assessed coagulation in vitro by thrombin generation using the Calibrated Automated Thrombogram. Thrombin generation was evaluated by lag time, time to thrombin peak, thrombin peak, and endogenous thrombin potential in response to tissue factor (1 pm). In vivo coagulation assessment was based on levels of prothrombin fragment 1 + 2 (F1 + 2) (thrombin generation) and D-dimer (fibrin turnover).Clinical Trial Registration: NCT02352090.Results: Lag time and time to thrombin peak remained unaltered after exposure to EV + DNG, whereas EE + DNG shortened both lag time (mean percentage change -24%, 95% confidence interval [CI] -32% to -15%; p < 0.01) and time to thrombin peak (-26%, 95% CI -37% to -16%; p < 0.01). EV + DNG induced lower thrombin peak and endogenous thrombin potential than EE + DNG (peak; +45%, 95% CI 22%-67% vs +147%,95% CI 96%-198%; p < 0.01, and endogenous thrombin potential; +26%, 95% CI 15%-38% vs +64%, 95% CI 51%-76%; p < 0.01). Median F1 + 2 levels remained unchanged with EV + DNG (p = 0.22) but increased within normal ranges with EE + DNG (from 152 pmol/L, 95% CI 127-206] pmol/L to 194 pmol/L, 95% CI 149-250 pmol/L, p = 0.04). The within-group change in D-dimer levels was not significant in any of the groups. DNG alone did not affect these biomarkers.Conclusions: Both in vitro and in vivo thrombin generation was lower after exposure to EV + DNG compared with EE + DNG. The lower thrombin generation measures after treatment with EV + DNG indicate less enhancement of coagulation potential and suggest that EV may be favorable to EE as a component of combined oral contraceptives. [ABSTRACT FROM AUTHOR]

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

Bleeding irregularities are one of the major reasons for discontinuation of oral contraceptives (OCs), and therefore clinicians need to set expectations during consultations. In this review we provide an overview of bleeding data of recently marketed cyclic combined OCs (COCs) and one progestin-only pill (POP). We evaluated data from phase 3 trials (≥12 months) used to gain regulatory approval. Overall, each type of OC has its own specific bleeding pattern. These patterns however were assessed by using different bleeding definitions, which hampers comparisons between products. In COCs, the estrogen balances the effects of the progestin on the endometrium, resulting in a regular bleeding pattern. However, this balance seems lost if a too low dose of ethinylestradiol (EE) (e.g., 10 µg in EE/norethindrone acetate 1 mg) is used in an attempt to lower the risk of venous thromboembolism. Replacement of EE by 17β-estradiol (E2) or E2 valerate could lead to suboptimal bleeding profile due to destabilization of the endometrium. Replacement of EE with estetrol (E4) 15 mg in the combination with drospirenone (DRSP) 3 mg is associated with a predictable and regular scheduled bleeding profile, while the POP containing DRSP 4 mg in a 24/4 regimen is associated with a higher rate of unscheduled and absence of scheduled bleeding than combined products. [ABSTRACT FROM AUTHOR]

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

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

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

Background: The aim of this study was to investigate whether the prevalence and the therapy patterns of endometriosis differ in 2010 and 2019. Materials and Methods: This retrospective cross-sectional study was based on the data from the IQVIA Disease Analyzer database and included women with at least one visit to one of the 136 private gynecologist practices in Germany in 2010 or 2019. The prevalence of endometriosis as well as prevalence of each endometriosis therapy such as Dienogest, other Progestins than Dienogest, and Gonadotropin-Releasing Hormones, was calculated in both years. Results: The present study included 346,249 women documented in 2010 and 343,486 women documented in 2019. The prevalence of endometriosis increased from 0.53% in 2010 to 0.66% in 2019 (P<0.001). The proportion of endometriosis patients treated with Dienogest increased significantly between 2010 and 2019 (18.1 vs. 35.0%). The proportion of women prescribed other Progestins than Dienogest has not significantly changed between 2010 and 2019 (8.4 vs. 8.3%). Gonadotropin-releasing hormones were prescribed only rarely in both 2010 and 2019, with a significant decrease in prescriptions between these two years (3.7 vs. 2.0%). Conclusion: There were significant changes in the prevalence and medical therapeutic patterns of endometriosis in 2010 versus 2019 reflecting changes in therapy guidelines and possibly in diagnostic methods. [ABSTRACT FROM AUTHOR]

Objective: Metabolic effects of dienogest (DNG) may lead to unintended lipid levels, which may predispose to cardiovascular diseases. The main objective of this study was to reveal effects of DNG only treatment on lipid profile. Methods: Thirty three otherwise healthy women with diagnosed endometriosis were started on 2 mg dienogest/day oral treatment. Blood samples were taken before and after 6 months of therapy to measure triglycerides (TG) low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and total cholesterol levels. Exclusion criteria were withdrawal from DNG treatment, pregnancy, women with incomplete medical records or who were lost to follow-up, allergies for DNG, need for laparoscopy during the 6-month of medical treatment, having familial lipid disorders, and body mass index (BMI) >30 kg/m2. Results: There was no significant difference regarding total cholesterol, HDL, and LDL levels between the blood samples taken before and after DNG treatment. However, TG levels were significantly higher at 6th-month blood samples than the pre-DNG blood samples (94 vs. 75, p=0.03). The mean age was 31.4±4.8 years, gravidity was 1.8±1.3, parity was 1.6±1.1, and BMI was 24.6±1.8 (kg/m²). Conclusion: Our results suggest that DNG treatment increases TG levels. The metabolic effects of DNG should be clarified as being widely used among women as a progestin-only regimen. Alterations in lipid metabolism may affect the use of this drug in patients with metabolic syndrome or hyperlipidemia. [ABSTRACT FROM AUTHOR]

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

40 歳以上の子宮内膜症に対する薬物療法について，progestin 製剤および GnRH antagonist 製剤の有 用性につき検討した．薬物療法が必要な 40 歳以上の患者 40 例を対象とし，A: dienogest（D）を投与 した群（22 例），および B: GnRH antagonist（G）を投与した群（18 例）に分け，治療開始後 3，6 ヵ月の後の下腹痛の改善度，血中 estradiol 値の変動および不正子宮出血の出現頻度につき比較検討し た．下腹痛は，両群ともに改善していた．血中 estradiol 値は B 群で有意に低下していた（p＜0.05）． A 群では 22 例中 6 例（27.3％）に不正子宮出血が出現したが，B 群では 1 例も出現しなかった．卵 巣欠落症状は両群とも発生しなかった．40 歳以降の子宮内膜症に対しては，D のみではなく G の間 隔を空けた投与法も有用である． [ABSTRACT FROM AUTHOR]

Purpose: To investigate the histological efficacy of ranibizumab and zoledronic acid in an experimentally induced endometriosis model as compared with danazol, buserelin acetate and dienogest. Methods: Endometrial implants were introduced in 52 female Wistar albino rats, which were then randomly divided into six groups. The animals were, respectively, given dienogest, danazol, buserelin acetate, zoledronic acid, ranibizumab and 0.9% NaCl. After 4 weeks, the volumes and histopathological properties of the implants were evaluated and the implants were excised completely at the third laparotomy. A histopathological scoring system was used to evaluate the preservation of epithelia. Endometrial explants were evaluated immunohistochemically. Results: Among the groups, the histological score was significantly lower in the zoledronic acid and ranibizumab groups compared with the controls (p < 0.001). There were no significant differences regarding ellipsoidal volume levels between groups (p > 0.05). However, there was a statistically significant difference regarding cell numbers according to the degree of Bcl-2, NF-κB, and CD31 staining (p < 0.001). There was no statistically significant difference in Bcl-2, CD31, or NF-κB staining in the binary comparisons between the other groups (p > 0.05). For Bcl-2 staining, the staining rate of the group treated with zoledronic acid was significantly lower compared with the dienogest and danazol groups (p < 0.05). The staining rates of CD31 and NF-κB were significantly lower in the zoledronic acid and ranibizumab groups compared with the controls (p < 0.05). Conclusion: According to these results, zoledronic acid and ranibizumab may be putative candidates for the treatment of endometriosis. [ABSTRACT FROM AUTHOR]

Objective: To compare the effects of dienogest and a combined oral contraceptive pill (COCP) after laparoscopic surgery on pain and quality of life in women with severe endometriosis. Methods: A randomized double‐blind pilot study was conducted from March 2018 to March 2020 in women with severe endometriosis confirmed by laparoscopic surgery. A total of 108 patients who had undergone laparoscopic surgery received dienogest, COCP, or placebo daily for 6 months. Primary and secondary outcomes were compared between the three groups. Results: Treatment with dienogest or COCP was associated with improved self‐reported pain after 6 months of treatment, as evidenced by significantly lower scores for pelvic pain and dyspareunia compared with placebo (P < 0.05). Significant differences in overall quality of life score were observed over 6 months in the dienogest, COCP, and placebo groups (mean difference 22.00, 23.45, and 6.45 points, respectively; P < 0.001). Post‐hoc analysis revealed a significant difference in overall quality of life score between the placebo group and the dienogest (P < 0.001) and COCP groups (P = 0.004). Conclusion: Postoperative administration of dienogest or COCP reduced endometriosis‐associated pain and improved quality of life in women with severe endometriosis. Clinical trials registration: https://en.irct.ir/trial/43070. Synopsis: Postoperative administration of dienogest or the combined oral contraceptive pill is an effective treatment with few adverse effects, reduced endometriosis‐associated pain, and improved quality of life. [ABSTRACT FROM AUTHOR]

Introduction: Women with endometriosis require individualized, long-term treatment. Analyzing prescription choices, medication switches, discontinuations, and breaks can describe real-world treatment patterns and optimize pathways for women. To our knowledge, the Vi sanne P ost-approval O bservational S tudy (VIPOS) is the largest real-world, non-interventional study examining the safety of hormonal treatments for the routine clinical management of endometriosis. We present data from VIPOS on endometriosis drug utilization patterns, including treatment discontinuation due to treatment failure. Methods: VIPOS was a prospective, long-term, controlled, non-interventional cohort study in six European countries (Germany, Switzerland, Russia, Poland, Ukraine, and Hungary) conducted between 2010 and 2018. Women self-reported medical and gynecological history and symptoms and treatment information via comprehensive questionnaires. Results: Overall, 27,840 women were enrolled via gynecologists or specialized centers. Inter-country variance in treatment prescription patterns suggests the influence of differential management strategies and guidelines on prescribing behavior and diagnostic methods. Most enrolled women were receiving combined hormonal contraceptives. Women receiving dienogest 2 mg or gonadotropin-releasing hormone agonists more often had a surgical diagnosis of endometriosis compared to other treatments, while most women receiving combined hormonal contraceptives, other progestins or danazol had a symptom-based diagnosis. Although treatment changes during follow-up were common, only 4733 discontinuations out of 42,342 treatment starts were reported due to side effects or treatment ineffectiveness. Conclusion: VIPOS provides valuable insights into the considerable inter-country variance in endometriosis treatment prescription and potential role of differing management guidelines and practices strategies. Findings presented here suggest the need greater alignment of clinical practice to optimize patient management. [ABSTRACT FROM AUTHOR]

Objective: To compare the efficacy of dienogest with the combined oral contraceptive pill (COC) Yasmin for the control of endometriosis-associated pelvic pain.Study Design: Seventy women with endometriosis-associated chronic pelvic pain, dysmenorrhoea or both for >6 months were randomized to either dienogest (Visanne) 2 mg/day or monophasic COC (Yasmin, 0.03 mg ethinyl estradiol and 3 mg drospirenone) for 24 weeks. The primary efficacy variable was change in non-cyclic pelvic pain and dysmenorrhoea from baseline to end of treatment, assessed using a visual analogue scale (VAS). The secondary efficacy variable was change in the Biberoglu and Behrman (B&B) scale scores for chronic pelvic pain, dysmenorrhoea and dyspareunia. Health-related quality of life (HRQoL) was evaluated using the Endometriosis Health Profile-30 (EHP-30) questionnaire at baseline and 24 weeks. Safety variables included incidence of side-effects, bleeding pattern and treatment tolerability.Results: Both treatments improved the mean VAS score for endometriosis-associated pelvic pain significantly: mean difference 6.0 [95% confidence interval (CI) 4.9-7.1; p < 0.0001] in the dienogest group and 4.54 (95% CI 3.1-5.9; p < 0.0001) in the COC group; the difference between them was not significant (p = 0.111). Similarly, both dienogest and COC improved HRQoL in various core and modular segments of the EHP-30 questionnaire with comparable requirements for supplemental pain medication (p = 0.782 and 0.258 at 12 and 24 weeks, respectively), and redistribution of the B&B severity profile for chronic pelvic pain (p = 0.052 and 0.526 at 12 and 24 weeks, respectively), dysmenorrhoea (p = 0.521 and 1 at 12 and 24 weeks, respectively) and dyspareunia (p = 0.376 and 0.835, respectively). Nevertheless, dienogest was associated with fewer side-effects, and hence had a better safety and tolerability profile than COC.Conclusions: Dienogest (2 mg/day) is comparable to the COC Yasmin for the relief of endometriosis-associated pelvic pain and improvement in HRQoL.Clinical Trial Registration: Clinicaltrials.gov under number NCT04256200; date of registration 15/1/2020 (registered retrospectively). [ABSTRACT FROM AUTHOR]