Dienogest Research Articles

Long-Term Administration of Dienogest for the Treatment of Pain and Intestinal Symptoms in Patients with Rectosigmoid Endometriosis

Background: Rectosigmoid endometriosis is a severe form of deep endometriosis, which may be responsible for pain symptoms and a wide range of intestinal complains such as diarrhea, constipation, and abdominal cramping. The primary objective of this study was to evaluate the efficacy of long-term therapy with dienogest (DNG), a fourth-generation progestin, for ameliorating quality of life, pain, and intestinal symptoms of patients affected by rectosigmoid endometriosis. Methods: A retrospective analysis of a prospectively collected database was done on patients with endometriotic nodules infiltrating at least the muscular layer of the rectosigmoid wall with an estimated colorectal stenosis <60%. The diagnosis of rectosigmoid endometriosis was based on transvaginal ultrasonography. Patients accepting to participate in the study received continuous oral treatment with DNG at the dose of 2 mg/day. Results: At the end of the first year of treatment, a significant decrease in dysmenorrhea (P < 0.001), chronic pelvic pain (P < 0.001), dyspareunia (P < 0.001), dyschezia (P < 0.001), and in intestinal symptoms (P < 0.001) was observed. A progressive increase of the Endometriosis Health Profile-30 (EHP-30) and Gastrointestinal Quality of Life Index (GIQLI) scores was observed in the first two years of therapy (P < 0.001 and P < 0.001, respectively). Improvements of patients’ symptoms and quality of life were maintained until the end of the study. The regimen was well tolerated, and the frequency and amount of irregular bleeding decreased as treatment progressed. Conclusion: The current study confirms the efficacy of long-term therapy with DNG for treating symptoms caused by rectosigmoid endometriosis.

Effects of new generation progestins, including as mixtures and in combination with other classes of steroid hormones, on zebrafish early life stages

Fish are exposed to progestins and steroid mixtures in contaminated waters but the ecotoxicological implications are not sufficiently known. Here we analyze effects of the new generation progestin dienogest (DNG) followed by investigating effects of mixtures of new generation progestins containing DNG, cyproterone acetate and drospirenone and the hormone progesterone. Furthermore, effects of this mixture were studied after adding 17β-estradiol (E2) and clobetasol propionate (CLO) in zebrafish embryos and larvae at concentrations between 0.01 and 10 μg/L. DNG showed only very minor transcriptional alterations among the 24 assessed genes with downregulation of the fshb transcript only. The progestin mixture caused weak induction of the lhb, cyp2k22 and sult2st3 transcripts. Addition of E2 to the mixture caused strong induction vtg1, cyp19b, esr1 and lhb, as well as downregulation of fshb from 0.01 μg/L onwards. Besides altering the same transcripts, addition of CLO altered glucocorticoid regulated genes mmp-9, mmp-13, g6pca, fkbp5 and irg1l. While each steroid class exhibited its specific activity independently in the mixture, sult2st3 and cyp2k22 were regulated by both E2 and CLO. Furthermore, CLO alone and in mixtures decreased spontaneous muscle contractions, increased heartrate and induced edema. Our study highlights the prominent effects of E2 and CLO in environmental steroid mixtures, while new generation progestins show relatively low activity.

The clinical outcome of Dienogest treatment followed by in vitro fertilization and embryo transfer in infertile women with endometriosis

BackgroundEndometriosis is considered to be the most intractable cause of female infertility. Administering any type of treatment for endometriosis before in vitro fertilization and embryo transfer (IVF-ET) is an important strategy for improving the IVF-ET outcomes for infertile women with endometriosis. In fact, treatment with a gonadotropin-releasing hormone (GnRH) agonist just before IVF-ET has been reported to improve the clinical outcome in endometriosis patients. However, the benefit of Dienogest (DNG), a synthetic progestin, treatment just before IVF-ET remains unclear.MethodsSixty-eight infertile women with Stage III or IV endometriosis (ovarian endometrial cyst < 4 cm) were recruited for this study. The subjects were divided into 2 groups: a DNG group (n = 33) and a control group (n = 35). DNG was administered orally every day for 12 weeks prior to the conventional IVF-ET cycle in the DNG group. Standard controlled ovarian hyperstimulation with the GnRH agonist long protocol was performed in the control group. The numbers of mature follicles and retrieved oocytes, fertilization rates, implantation rates, and clinical pregnancy rate were compared between the two groups. In addition, the concentrations of inflammatory cytokines, oxidative stress markers, and antioxidants in follicular fluids were also measured.ResultsThe numbers of growing follicles, retrieved oocytes, fertilized oocytes, and blastocysts were significantly lower in the DNG group than in the control group. The fertilization and blastocyst rates were also lower in the DNG group than in the control group. Although there was no significant difference in the implantation rate between the groups, the cumulative pregnancy rate and live birth rate were lower in the DNG group than in the control group. There was no significant difference in the abortion rate. Our results failed to show that DNG reduces the inflammatory cytokine levels and oxidative stress in follicular fluids.ConclusionsAdministering DNG treatment just before IVF-ET did not provide any benefits to improve the clinical outcomes for infertile women with endometriosis.

Subtype I (intrinsic) adenomyosis is an independent risk factor for dienogest-related serious unpredictable bleeding in patients with symptomatic adenomyosis

We aimed to retrospectively analyze the risk factors of a continuous dienogest (DNG) therapy for serious unpredictable bleeding in patients with symptomatic adenomyosis. This is a retrospective study based on data extracted from medical records of 84 women treated with 2 mg of DNG orally each day between 2008 and 2017. 47 subjects were excluded from the original analyses due to an inadequate subcategorization into subtype I and subtype II and a lack of hemoglobin levels. The influence of various independent variables on serious unpredictable bleeding was assessed. Of the 37 eligible patients who received the continuous DNG therapy, 14 patients experienced serious unpredictable bleeding. Univariate analysis revealed that the serious bleeding group had subtype I adenomyosis (P = 0.027). There was no correlation between age, parity, minimum hemoglobin level before treatment, previous endometrial curettage, and duration of DNG administration, or uterine or adenomyosis size and the serious bleeding. A DNG-related serious unpredictable bleeding is associated with the structural type of adenomyosis (subtype I) in patients with symptomatic adenomyosis.

1355 To Evaluate the Difference of the Efficacy of Usual Cyclic Low-Dose Monophasic Oral Contraceptive (OC) Versus Dienogest (DNG) Hormonal Therapy in the Recurrence of after Laparoscopic Excision of Ovarian Endometrioma

Study Objective To evaluate the efficacy of usual cyclic low-dose monophasic oral contraceptive (OC) use versus dienogest (DNG) in the recurrence of endometrioma after surgery. Design Retrospectively reviewed. Setting 155 patients aged from 20 years old to 40 years old who underwent laparoscopic excision of ovarian endometriomas in the department of obstetrics and gynecology of Toho University sakura medical center between April 2009 and March 2015. Patients or Participants All patients were reproductive-aged women with regular menstruation and did not want to get pregnant promptly after surgery. Interventions In the presence of endometrioma, cystectomy was performed and resection of all visible endometriosis was performed with the use of standard laparoscopic equipment. Following surgery, patients chose to receive OC, DNG for 1 year or no medication. The patients were evaluated at 3-month intervals during the following years after surgery. The recurrence rate was observed at 36 months postoperatively. Measurements and Main Results A significant reduction in recurrence rate was evident in OC and DNG users versus nonusers at 36 months postoperatively. Postoperative DNG use dramatically decreased the risk of ovarian endometrioma recurrence. Overall, there were no differences between the no recurrence and recurrence groups in terms of age, BMI, or tumor size. It was also noted that most of the OC user recurrent endometriomas were bilateral, multilocular, associated with DIE and stage IV by rASRM classification. Conclusion A significant reduction in recurrence rate was evident in OC and DNG users postoperative hormonal therapy. The stage and severity of endometriosis was significant higher in OC user recurrence group. Therefore, DNG therapy is the best option for prevention of recurrence.

Effects of dienogest on breast : MCF cell line data

Dienogest (DNG) is a widely used progestin which is safe and effective for long-term management of endometriosis. However, its association to breast cells remains to be elucidated. We perform this study to investigate whether in vitro treatment of DNG can cause any biologic changes on MCF cell line (human estrogen receptor (ER)-positive breast cancer cell line) experiments. A laboratory study. Following in vitro culture of MCF cells, we treated those cells and compared cell viability and the expression of several markers have shown to be increased in breast cancer cells between with estradiol alone and estradiol with DNG. Cell viability was measured utilizing MTT(3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and the expression of PCNA (proliferating cell nuclear antigen) and PAK4 (p21 activated kinase 4) was measured by western blot analyses. VEGF (vascular endothelial growth factor) and IL (interleukin)-32 were analyzed by ELISA, and MMP2 (matrix metalloproteinase 2) activity was assayed by zymography. In vitro treatment of MCF7 cells led to an increased cell viability by estradiol alone and decreased by both estradiol and DNG after 24 and 48-hour culture. The expression of PCNA after 48 hours showed the same result. VEGF and IL-32 were also significantly increased with estradiol and decreased following DNG treatment. However, there was no significant changes in MMP2 activity and PAK4 expression. These findings suggest that DNG may have inhibitory effects on carcinogenesis of breast cells by suppressing specific biologic changes treated by estradiol. However, further study is necessary using normal human breast cells.

Effects of long-term treatment with Dienogest on the quality of life and sexual function of women affected by endometriosis-associated pelvic pain.

PurposeThe aim of this prospective study was to evaluate quality of life (QoL) and sexual function of women affected by endometriosis pain treated with Dienogest (DNG) for 24 months.Patients and methodsFifty-four women constituted the study group and were given DNG 2 mg/daily; 38 women were given non-steroidal anti-inflammatory drugs (NSAIDs) and constituted the control group. To define endometriosis-associated pelvic pain, dysmenorrhea and dyspareunia the Visual Analogic Scale (VAS) was used. The Short Form-36 (SF-36), the Female Sexual Function Index (FSFI) and the Female Sexual Distress Scale (FSDS) were used to assess the QoL, sexual function and the sexual distress, respectively. The study included five follow-ups at 3, 6, 12, 18 and 24 months.ResultsSlight improvements in chronic pelvic pain, dysmenorrhea and dyspareunia were observed in the study group at 3 months (p<0.05) and improved more from 6 to 24 months of DNG treatment (p<0.001). QoL improved with a similar trend: at 3 months the improvement was significant in several categories (p<0.05), and from 6 to 24 months in all categories (p<0.001). The FSFI score did not change at the 3 month follow-up (p=not significant [NS]) but it improved from 6 to 24 months (p<0.001). A similar trend was observed for the FSDS score (p<0.001). No change was observed in the control group (p=NS).ConclusionLong-term treatment with DNG 2 mg once-daily in women with endometriosis-associated pelvic pain may have positive effects on the QoL and sexual life, confirming the observations of the previous study on the first 6 months of treatment.

Effects of long-term use of dienogest after surgery on bone mineral density in patients with ovarian endometrioma

Objective: The current treatment strategy for endometriosis includes the long-term medical suppression after surgery to prevent the recurrence of symptoms and lesions. Several studies have demonstrated the efficacy, safety and tolerability of dienogest (DNG) for the treatment of endometriosis. As DNG inhibits ovulation, there could be concern about its negative effect on bone health, especially with long-term use. This study was performed to evaluate the effects of long-term postoperative use of DNG on bone mineral density (BMD) in patients with ovarian endometrioma.

Contraception with estradiol valerate and dienogest: adherence to the method.

Purpose: The aim of the study was to examine the discontinuation rate of hormonal contraception with estradiol valerate (E2V) and dienogest (DNG).Patients and methods: We collected data at the Family Planning Clinics of the Departments of Obstetrics and Gynecology of Pisa and Cagliari. We included in the analysis 354 consecutive women using oral contraceptive pills containing E2V and DNG. We analyzed the rate and the reason for discontinuation, classifying the reasons in 5 categories: 1) minor side effects, 2) adverse events, 3) other events not directly caused by the drug or conditions for which the pill could represent a risk factor, 4) no compliance with the method and 5) no further need.Results: Of the 354 women examined, 50.8% had discontinued E2V/DNG pill. Excluding women who stopped the pill because of no further need (10.5%), 27.4% discontinued because of minor side effects, 1.7% discontinued for adverse events, 9.9% because of other events not directly caused by the drug or conditions for which the pill could represent a risk factor and 1.4% because of difficulties with compliance. Irregular bleedings were the main reasons reported for discontinuation. The time to discontinuation for irregular bleedings was significantly (p<0.02) longer in adults than in adolescents and slightly but not significantly longer in women who received information about this possible effect.Conclusion: Unacceptable cycle control was the principal cause of discontinuation of pill with E2V and DNG. An appropriate information about this possible effect may improve adherence to this combined oral contraceptive.

Overview of the therapeutic possibilities of combined oral contraceptive containing estradiol valerate and dienogest

Taking into account that the frequency of abortions in Russia today remains quite high, the strategy of fertility regulation through the provision of contraceptive advice to women of various ages comes to the fore. It has been proven that combined oral contraceptives are the most effective method of preventing unwanted pregnancies. An innovative combination of oral contraceptives containing estradiol valerate (EV) and dienogest (DNG) dynamically provides effective inhibition of ovulation and sufficient cycle control. DNG/EV has high efficacy, acceptability and tolerability and can be successfully used in sexually active women in need of contraception, regardless of their age. Like any modern contraceptive, this drug possesses a whole arsenal of pronounced therapeutic possibilities, which can be used in real clinical practice. In addition, the combination of EV and DNG is highly effective in the therapy of menorrhagia. The percentage of patients who had successful treatment and resulted in a decrease in menstrual blood loss was high. The effectiveness of the drug is confirmed by the bleeding of withdrawal at the end of the first treatment cycle and continues to increase gradually with further administration.

Comparison of long-term use of combined oral contraceptive after gonadotropin-releasing hormone agonist plus add-back therapy versus dienogest to prevent recurrence of ovarian endometrioma after surgery

ObjectiveThe aim of this study was to compare long-term use of combined oral contraceptive (COC) after gonadotropin-releasing hormone (GnRH) agonist plus add-back therapy with dienogest (DNG) treatment as medical treatments after surgery for ovarian endometrioma. MethodsThis prospective cohort study analyzed 52 reproductive-aged women who underwent surgery for ovarian endometrioma and received postoperative medical treatment with either COC after GnRH agonist (n = 20) or DNG (n = 32) for 24 months. Changes in quality-of-life (QOL) and bone mineral density (BMD) were compared according to treatment. In addition, recurrence of pain and lesions were compared. ResultsBaseline characteristics did not differ in demographic profiles and factors associated with endometriosis or QOL. During 24 months of treatment, no differences in any component of QOL were found between the two groups. BMD at the lumbar spine significantly decreased after the first 6 months of treatment in both COC after GnRH agonist (−3.5%) and DNG (−2.3%) groups, but the groups did not differ statistically. After 6 months, further decrease in BMD was not observed until 24 months in both groups. In addition, no cases of pain or endometrioma recurrence were found. ConclusionOur results suggest that long-term use of COC after GnRH agonist plus add-back therapy is comparable to dienogest as a long-term postoperative medical treatment for endometriosis.

Combined oral contraceptives with natural estrogen and sexual function: the optimal method of contraception for women of different ages

Background. Combined oral contraceptives (COCs) are the most common method of prevention of unwanted pregnancies in women from the early reproductive period to perimenopause, therefore their impact on quality of life, sexual function and general well-being remains the subject of active discussion. Some studies revealed various manifestations of sexual dysfunction in patients receiving COCs, therefore such questions, as well as the advantages / disadvantages of individual components (their type and dose) of drugs, are of interest to the clinician. Aim. Assess mechanisms of influence of COCs on female sexual function. Materials and methods. In order to write this review domestic and foreign publications were searched in Russian and international search systems (PubMed, elibrary, etc.) for the last 2-15 years. Relevant articles from the peer-reviewed literature were included. Results. Many studies proved a beneficial effect of estradiol valerate (E2V) which is estrogen identical to natural one in a combination with dienogest (DNG) which is 4th generation progestin in a dynamic dosing regimen on quality of life and sexual function. This beneficial effect is achieved due to combined effects of both components of the drug as well as its reception mode. Conclusion. The combination of estradiol valerate (E2V) which is estrogen identical to natural one with dienogest (DNG) which is 4th generation progestin may be the optimal method of contraception for women of any age, including the young, with decreased libido while taking other COCs.

When Solving Dyspareunia Is Not Enough to Restore Sexual Function in Women With Deep Infiltrating Endometriosis Treated With Dienogest

The aim of the study was to evaluate dyspareunia and sexual function (SF) in women with deep infiltrating endometriosis (DIE) who were treated with dienogest (DNG) for 12 months. The prospective cohort study took place at the University of Campinas, Brazil, and included 30 women with sonographic diagnosis of DIE and sexual dysfunction treated with 2 mg/daily DNG for 12 months. SF parameters were assessed by the Female Sexual Function Index (FSFI) before and after treatment, and dyspareunia was quantified through the visual analog scale (VAS) during the follow-ups performed every three months. Statistical analysis was performed by ANOVA test and through the use of software SAS, Version 9.4. Women were on average 36.13 ± 6.24 years old, and all of them showed sexual dysfunction (FSFI =17.6 ± 5.7) before DNG; 88.3% had dyspareunia as the main symptom related to DIE (VAS before: 5.3 ± 3.1). At the end of the treatment, dyspareunia showed a decrease of intensity (VAS after: 3.7 ± 3.3; p = .0093) and an improvement on FSFI index was accomplished (p = .0023); however, it did not restore SF completely, considering the FSFI cutoff < 26.55. Long-term treatment for DIE with DNG has provided a decrease in dyspareunia and also an enhancement of SF, although SF has not been restored to normal levels.

Effectiveness of Dienogest for Treatment of Recurrent Endometriosis: Multicenter Data.

This study aimed to assess whether dienogest (DNG) is also effective in patients with recurrent endometriosis based on multicenter data of 121 women who were clinically diagnosed as having recurrent endometriosis and treated for more than 24 weeks with DNG (2 mg daily). We evaluated the changes in endometriosis-associated pain scores (visual analog scale [VAS]), serum cancer antigen 125 (CA-125) levels, and endometrioma sizes following DNG medication in these women along with adverse events associated with DNG medication. The mean duration of DNG treatment was 57.80 (24.08) weeks, and during continuation of DNG, the mean VAS score was 5.03 (1.73) at baseline and significantly decreased to 2.46 (1.32) at 24 weeks after taking DNG. In subgroup analysis, the trend of pain-related symptoms was compared between the symptom-only recurrence group and the recurrent endometrioma group. In both groups, the pain scores decreased significantly during the first 24 weeks but remained relatively unchanged thereafter. Moreover, the size of recurrent endometriomas and CA-125 levels also decreased significantly compared to baseline. The mean size of recurrent endometriomas was 3.77 (1.59) cm in diameter and decreased to 2.74 (1.53) cm after 24 weeks of DNG treatment ( P for trend < .001). The mean CA-125 level was 80.04 U/mL at baseline and significantly decreased to 33.11 U/mL after taking DNG for 24 weeks and lasted until 72 weeks ( P for trend = .0288). Overall, 51 (42.15%) patients reported adverse events, and the most common one was irregular bleeding pattern (29.75%, 36/121). In conclusion, DNG was found to be effective in reducing the size of endometriomas and provided symptomatic relief in this cohort of women with recurrent endometriosis.

ASSESSMENT OF EFFICIENCY OF ANTI-RELAPSE THERAPY WITH DIENOGEST AFTER SURGERY TREATMENT OF WOMEN WITH COLORECTAL ENDOMETRIOSIS

Purpose of research. To analyze reproductive outcomes and relapses of endometriosis in women after surgical treatment of colorectal endometriosis depending on hormonal therapy.Materials and methods. The article includes data on reproductive outcomes and recurrence of endometriosis in women undergoing surgical treatment for colorectal endometriosis in the surgical department of Kulakov National Medical Research Centre for Obstetrics, Gynaecology and Perinatology from 2014 to 2016. As an anti-relapse therapy, the first group of women received dienogest (DNG) at a dose of 2 mg/day, the second group included women who received a combined oral contraceptive containing DNG 2 mg + ethinyl estradiol (EE) 0.03 mg for the period of rehabilitation or prior to planning of pregnancy. The comparison group consisted of women who did not receive hormonal drugs in the postoperative period. Data on side effects and tolerability of the drug are also described.Results. During the follow up period from 12 to 48 months, 51 patients were selected for this study, 14 patients were included in the first group, 18 patients were in the second group, 19 patients were in the comparison group. There were no differences in the overall rate of pregnancy depending on the choice of tactics of postoperative management. The highest number of pregnancies (92.3%) occurred during the first year after surgery, which suggests the effect of the duration of hormone therapy on the probability of pregnancy. The lowest number of relapses was registered in the group of long-term monotherapy of DNG. In the group of DNG monotherapy a greater number of side effects were noted, which in most cases did not cause significant discomfort to patients.Conclusion. Long-term administration of DNG at a dose of 2 mg/day after surgical treatment of colorectal endometriosis is an effective means of preventing relapses with good tolerability. However, in some women planning a pregnancy, it may be rational to abandon hormone therapy in favor of earlier pregnancy planning.

Effects of different progestins on prostaglandin biosynthesis in human endometrial explants

ObjectiveTo compare the effects of chlormadinone acetate (CMA), dienogest (DNG) and drospirenone (DRSP) on prostaglandin biosynthesis in a human endometrial explants model. Study designHuman endometrial explants obtained by aspiration curettage and human endometrial YHES cells were stimulated with interleukin-1β (IL-1β) and exposed to CMA, DNG, DRSP or dexamethasone (DEX; YHES cells). Cellular messenger RNA (mRNA) levels of cyclooxygenase-2 (COX-2) were analyzed by reverse-transcription quantitative real-time polymerase chain reaction. Concentrations of prostaglandin F2α (PGF2α) in culture supernatants were measured by enzyme-linked immunosorbent assay. ResultsCMA exerted after IL-1β stimulation a stronger down-regulation of COX-2 mRNA compared to DNG and DRSP in human explants (−55% vs. −40% and 46%, respectively). The effect of CMA on COX-2 mRNA was significantly stronger (p=.025) than that of DNG. Moreover, the effect of CMA was independent from cycle phase or presence of endometriosis. In order to evaluate the impact of the investigated progestins on effector molecules, PGF2α release was determined in supernatants. Again, CMA reduced the PGF2α release significantly by an average of −60% (p<.01). In contrast, no significant reduction was found for DNG and DRSP. In YHES cells, only DEX but not the progestins under study exerted a significant down-regulating effect (−79%, p<.01) on COX-2 mRNA after IL-1β stimulation. ConclusionAmong the tested progestins, CMA displayed the most consistent suppression of prostaglandin biosynthesis in human endometrial explants. ImplicationAmong three tested progestins, chlormadinone acetate had the most consistent suppressive effect on prostaglandins in endometrial explants. These findings support clinical observations about the efficacy of chlormadinone acetate in dysmenorrhea treatment.

Comparison of dienogest effects upon 3,3′–diindolylmethane supplementation in models of endometriosis and clinical cases

Dienogest (DNG) administration is a well-established treatment for endometriosis but bleeding irregularities remain its main disadvantage. Changes in diet, mainly to vegetable consumption, are beneficial in the treatment of estrogen-related pathologies but their use for endometriosis has been poorly studied. In this study, addition of the phytochemical 3,3′-diindolylmethane (DIM) to DNG therapy has been investigated in in vitro and ex vivo models for endometriosis and in a small cohort of women with endometriosis. Endometrial Ishikawa cells were treated with DNG or DIM at dosages from 10−10 M to 10−5 M for up to 72 h. Cell proliferation was measured by assessing BrdU incorporation. Endometrial tissue from women with endometriosis and controls was incubated with DNG or a combination of DNG and DIM. Tissue viability was determined using a modified colorimetric MTS assay. 17β-estradiol secretion was quantified by an electro-chemiluminescence immunoassay. Finally, DNG as monotherapy or in combination with DIM was randomly administered to women with endometriosis (n = 8) over 3 months. Bleeding patterns and associated pelvic pain were assessed by Visual Analogue Scale (VAS). DNG and DIM significantly reduced cell proliferation in Ishikawa cells. Ex vivo, DIM reduced viability and estradiol secretion specifically in endometriotic but not in normal endometrial tissue. This effect was enhanced by combination with DNG. Endometriosis associated pelvic pain was significantly reduced in patients taking the DNG-DIM combination therapy compared to those taking DNG alone. Bleeding pattern (number and duration of episodes) was significantly improved by addition of DIM to the DNG treatment. In conclusion, addition of DIM enhances effects of DNG ex vivo and may ameliorate bleeding patterns in endometriosis patients.

Efficacy and Safety of Estradiol Valerate/Dienogest for the Management of Heavy Menstrual Bleeding: A Multicenter, Double-Blind, Randomized, Placebo-Controlled, Phase III Clinical Trial.

To investigate the efficacy and safety of estradiol valerate (EV)/dienogest (DNG) for the management of heavy menstrual bleeding (HMB) in Asian and non-Asian women desiring contraception. In this multicenter, double-blind, phase III study, women were randomized 2:1 to receive EV/DNG or placebo tablets daily for seven 28-day cycles. The primary endpoint was the absolute change in menstrual blood loss (MBL) volume between the run-in and efficacy phases (90 days each). Secondary endpoints included the proportion of women with successful treatment (i.e., no episodes of MBL ≥80 mL and a decrease of <50% in MBL), percent change in MBL from the run-in phase, and change in hemoglobin and serum ferritin levels. Adverse events (AEs) were monitored throughout the study. Of the 341 women (mean age 34.7 ± 7.7 years; 309 Asians, 32 non-Asians) randomized, 270 completed the study. Mean reduction in MBL volume from run-in phase was significantly greater with EV/DNG than placebo (366.75 mL vs. 149.14 mL; p < 0.0001), with ∼52% and 12% of women, respectively, experiencing successful treatment. Percent decrease in MBL volume from the run-in phase was significantly greater with EV/DNG than placebo (63.5% vs. 24.8%; p < 0.0001). Hemoglobin and serum ferritin levels were increased with EV/DNG compared with placebo. Study drug-related AEs were reported in 16.3% and 8.2% of women with EV/DNG and placebo, respectively, none of which were of severe intensity. EV/DNG may be a safe and effective option in the treatment of HMB in Asian and non-Asian women who desire contraception.

Dienogest Versus Leuprolide Acetate for Recurrent Pelvic Pain Following Laparoscopic Treatment of Endometriosis.

To compare the efficacy and safety of dienogest (DNG) with depot leuprolide acetate (LA) in patients with recurrent pelvic pain following laparoscopic surgery for endometriosis. Prospective randomized trial. Zagazig University hospitals, Egypt. Two hundred and forty-two patients with recurrent pelvic pain following laparoscopic surgery for endometriosis. Dienogest (2mg/day, orally) or depot LA (3.75mg/4weeks, intramuscularly) for 12weeks. A visual analogue scale was used to test the intensity of pain before and after the end of treatment. There was highly significant reduction in pelvic pain, back pain and dyspareunia in both groups with mean of difference in dienogest group (28.7 ± 5.3, 19.0 ± 4.3 and 20.0 ± 3.08mm, respectively) and in LA group (26.2 ± 3.01, 19.5 ± 3.01 and 17.9 ± 2.9mm, respectively). The most frequent drug-related adverse effects in dienogest group were vaginal bleeding and weight gain (64.5 and 10.8%, respectively) which were significantly higher than LA group (21.5 and 3.3%, respectively). While the most frequent drug-related adverse effects in LA group were hot flushes and vaginal dryness (46.3 and 15.7%, respectively) which were significantly higher than dienogest group (15.7 and 3.3%, respectively). Daily dienogest is as effective as depot LA for relieving endometriosis-associated pelvic pain, low back pain and dyspareunia. In addition, dienogest has acceptable safety, tolerability and lower incidence of hot flushes. Thus, it may offer an effective and well-tolerated treatment in endometriosis.

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

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