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    Endometriosis: the effects of dienogest. Ferrero Simone,Remorgida Valentino,Venturini Pier Luigi,Bizzarri Nicolò BMJ clinical evidence INTRODUCTION:Ectopic endometrial tissue is found in 2% to 6% of women of reproductive age, in up to 60% of those with dysmenorrhoea, and in up to 30% of women with subfertility, with a peak incidence at around 40 years of age. However, symptoms may not correlate with laparoscopic findings. METHODS AND OUTCOMES:We conducted a systematic review and aimed to answer the following clinical question: What are the effects of dienogest for the treatment of endometriosis? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2014 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS:Five studies were included. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS:In this systematic review we present information relating to the effectiveness and safety of the following interventions: dienogest versus placebo or no treatment; dienogest versus gonadorelin analogues; dienogest versus combined oral contraceptives; dienogest versus other progestogens.
    Exploratory study of pre-surgical medications with dienogest or leuprorelin in laparoscopic cystectomy of endometrial cysts. Takenaka Motoki,Yano Ryuichiro,Hiraku Yuka,Shibata Mayuko,Hatano Kayoko,Yamamoto Shiori,Sato Kazuki,Yamamoto Kazushige,Morishige Ken-ichiro The journal of obstetrics and gynaecology research AIM:The aim of this study was to compare the effects of pre-surgical medication with dienogest or leuprorelin on post-surgical ovarian function. MATERIAL AND METHODS:We conducted an exploratory study in two centers in Japan that comprised 30 patients with ovarian endometrial cysts for whom surgical excision was planned. Patients were enrolled and divided into pre-surgical medication groups with dienogest or leuprorelin for 12 weeks. Thereafter, patients were treated by laparoscopic cystectomy. The primary outcome was ovarian function post-surgery, as assessed by serum anti-Müllerian hormone (AMH) level, antral follicle count (AFC) and resumption of menses. Secondary outcome was the effect of pre-surgical medication, as assessed by the size of endometrial cysts and visual analog scale (VAS) score. Serum AMH, AFC, size of endometrial cysts, and VAS scores were measured at baseline (before medication), after medication (1 day before surgery), and at 4 and 12 weeks post-surgery. RESULTS:Serum AMH levels did not change after pre-surgical medication with either dienogest or leuprorelin. Although AMH decreased after surgery, it recovered by 12 weeks post-surgery in both groups with no statistically significant difference. Mean AFC did not change after surgery in either group. Menses returned by 12 weeks post-surgery in all patients except for those who were pregnant. The rate of reduction of endometrial cyst volume did not differ between the groups. Both dienogest and leuprorelin were associated with substantial reductions in VAS scores. CONCLUSION:There were no statistically significant differences between pre-surgical medication with dienogest and leuprorelin in post-surgical ovarian function. Both medications were effective in reducing endometrial cyst volume and VAS score. 10.1111/jog.12701
    Evaluation of the efficacy, safety, and clinically recommended dose of dienogest in the treatment of primary dysmenorrhea: a randomized, double-blind, multicenter, placebo-controlled study. Osuga Yutaka,Hayashi Koichi,Kanda Shingo Fertility and sterility OBJECTIVE:To evaluate the efficacy, safety, and clinically recommended dose of dienogest (DNG; 0.5 mg/d, 1 mg/d, and 2 mg/d) in the treatment of primary dysmenorrhea. DESIGN:A phase II, randomized, double-blind, multicenter, placebo-controlled study. SETTING:Twenty study sites. PATIENTS:A total of 235 patients with primary dysmenorrhea. INTERVENTION(S):Patients were randomized to receive orally a placebo, DNG (0.5 mg/d, 1 mg/d, or 2 mg/d) or ethinylestradiol 0.02 mg/drospirenone 3 mg (an open-label reference drug) for 12 weeks. MAIN OUTCOME MEASURE(S):The primary endpoint was the change from baseline in the dysmenorrhea score at week 12 of treatment. The secondary endpoint was the change from baseline in the visual analogue scale at week 12 of treatment. Subjects were assessed for lower abdominal pain and/or low back pain. RESULTS:All DNG arms were superior to the placebo arm in terms of the change from baseline in the dysmenorrhea score. The results suggest an equal or greater effect of DNG 1 and 2 mg/d in relieving pain, when compared to the reference drug. In the safety profile of DNG, including irregular uterine bleeding, there was no obvious difference among the doses of DNG. A significant decrease in the serum estradiol concentration compared to that in the placebo arm was not observed in the DNG 1 mg/d arm but was observed in the DNG 2 mg/d arm. CONCLUSION(S):The results suggest that DNG at a dose of 1 mg/d is an effective and well-tolerated treatment for primary dysmenorrhea. TRIAL REGISTRATION:JapicCTI-152977 (en). 10.1016/j.fertnstert.2019.09.014
    Recurrence of uterine adenomyosis after administration of gonadotropin-releasing hormone agonist and the efficacy of dienogest. Matsushima Takashi,Akira Shigeo,Yoneyama Koichi,Takeshita Toshiyuki Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology This study elucidated the degree of adenomyosis recurrence following gonadotropin-releasing hormone agonist (GnRHa) discontinuation and dienogest efficiency for recurrent adenomyosis. This retrospective cohort study included 30 patients, divided into a group of patients whose progress was observed without providing additional therapy following GnRHa administration for six months (Group G) and a group of patients administered dienogest for six months following six months of GnRHa administration (Group D). Menorrhagia, dysmenorrhea, chronic pelvic pain, abdominal fullness, and uterine volume were recorded prior to treatment, six months after the start of therapy (6 M), and 12 months after the start of therapy (12 M). In Group G ( = 15), although all subjective symptoms disappeared at 6 M, nearly all symptoms recurred at 12 M. Uterine volume significantly decreased from 341.0 cm to 156.0 cm at 6 M ( = .001) and significantly increased again to 282.3 cm at 12 M ( = .003). In Group D ( = 15), all subjective symptoms disappeared at 6 M, and only abdominal fullness returned in a significant number of patients (5 of 5;  = .021) at 12 M. Uterine volume decreased significantly at 6 M ( = .003) and significantly increased again from 162.5 cm to 205.6 cm at 12 M ( = .006). Subjective symptoms, except for abdominal fullness, did not recur when dienogest was administered after GnRHa. 10.1080/09513590.2019.1683818
    Safety and Effectiveness of Dienogest (Visanne®) for Treatment of Endometriosis: A Large Prospective Cohort Study. Cho BaikSeol,Roh Ju-Won,Park Jonghoon,Jeong Kyungah,Kim Tae-Hee,Kim Yun Sook,Kwon Yong-Soon,Cho Chi-Heum,Park Sung Ho,Kim Sung Hoon Reproductive sciences (Thousand Oaks, Calif.) Dienogest (DNG) is a progestin with highly selective progesterone activity and known to be effective in the treatment of endometriosis. This prospective cohort study in patients who had been treated with DNG 2 mg (Visanne) for endometriosis was conducted to assess the safety and effectiveness of DNG in a large Korean cohort. This study included 3356 patients with endometriosis from 73 centers in Korea. All patients were treated with DNG 2 mg daily and were followed up for at least 6 months after initial visit. Any adverse events were recorded including severity, onset/closing date, outcomes, treatments, and the causality with DNG. Effectiveness of DNG was measured by changes in visual analogue scale (VAS) from baseline at the end of follow-up. The mean age of the subjects was 34.96 years, and the mean duration of treatment was 285.44 days. Incidence of adverse drug reaction (ADR) was 13.27% (413/3113). The most frequently reported ADR were "abnormal uterine bleeding" 4.14% (129/3113), "increased weight" 2.57% (80/3113), and "headache" 1.22% (38/3113). The number of patients (%) with favorable bleeding patterns was observed to increase as the duration of treatment increases. Amenorrhea was observed in 29.63%, 41.25%, 46.26%, and 53.20% of patients at 3 months, 6 months, 12 months, and more than 12 months follow-up period, respectively. The mean (±SD) VAS change from baseline at the last follow-up visit was -28.19 ± 28.39 mm (P value < 0.0001). This large cohort study confirms, in routine clinical practice, that DNG is safe and effective for treatment of endometriosis. 10.1007/s43032-019-00094-5
    A multicenter, randomized, placebo-controlled, double-blind, comparative study of dienogest at 1 mg/day in patients with primary and secondary dysmenorrhea. Osuga Yutaka,Hayashi Koichi,Kanda Shingo Fertility and sterility OBJECTIVE:To evaluate the efficacy and safety of dienogest (DNG), a progestational 19-norsteroid, in patients with primary and secondary dysmenorrhea. DESIGN:Phase III, randomized, double-blind, multicenter, placebo-controlled study. SETTING:Clinical study sites in Japan. PATIENT(S):Ninety-four women with dysmenorrhea. INTERVENTION(S):Random assignment to receive DNG (1 mg/day, orally) or placebo for 12 weeks; patients treated for anemia before randomization in cases of complicated anemia. MAIN OUTCOME MEASURE(S):Change in the dysmenorrhea score from baseline to week 12 of treatment with visual analog scale used for pain assessment. RESULT(S):The DNG group was superior to the placebo group in terms of the change from baseline in the dysmenorrhea score at week 12 of treatment in patients with dysmenorrhea. In both primary and secondary dysmenorrhea, the DNG group was superior to the placebo group for each diagnostic category. The mean serum estradiol concentrations were similar between the DNG and the placebo groups. Although the incidence of irregular uterine bleeding was higher in the DNG group, there were no severe or serious events. Most events of genital bleeding were spotting or breakthrough bleeding, suggesting DNG was well tolerated. CONCLUSION(S):In both primary and secondary dysmenorrhea, DNG at 1 mg/day relieved pain and was well tolerated. CLINICAL TRIAL REGISTRATION NUMBER:JapicCTI-173547(en). 10.1016/j.fertnstert.2019.11.010
    Endometrial preparation with Dienogest before hysteroscopic surgery: a systematic review. Laganà Antonio Simone,Vitale Salvatore Giovanni,Muscia Vincenzo,Rossetti Paola,Buscema Massimo,Triolo Onofrio,Rapisarda Agnese Maria Chiara,Giunta Loretta,Palmara Vittorio,Granese Roberta,Frangež Helena Ban,Romano Andrea Archives of gynecology and obstetrics PURPOSE:Hysteroscopic surgery is considered the gold standard for the minimal invasive treatment of many endouterine diseases such as endometrial polyps or submucous myomas. Recently, many studies have evaluated the effect of preoperative administration of a number of drugs to reduce endometrial thickness and achieve important intraoperative advantages. The purpose of this systematic review is to summarize the available evidence about the use of Dienogest, an orally administrable progestin, for endometrial preparation before hysteroscopic surgery. METHODS:All studies published on this topic and indexed on PubMed/MEDLINE, Embase or Google scholar databases were retrieved and analysed. RESULTS:We retrieved five studies about this topic. Considered together, the published data analyses allow us to conclude that Dienogest is effective in reducing the thickness of the endometrium, the severity of bleeding and also of operative time, with a lower number of side effects compared with other pharmacological preparations or no treatment. CONCLUSION:Administration of Dienogest may be an effective and safe treatment for endometrial thinning before operative hysteroscopy. However, this conclusion is based on few reports and further studies to prove or disprove it are warranted. 10.1007/s00404-016-4244-1
    Efficacy of dienogest in thinning the endometrium before hysteroscopic surgery. Kodama Michiko,Onoue Masayo,Otsuka Hirofumi,Yada-Hashimoto Namiko,Saeki Noriatsu,Kodama Takahiro,Wakasa Tomoko,Funato Takao Journal of minimally invasive gynecology STUDY OBJECTIVE:To investigate the efficacy of administration of dienogest to thin the endometrium before hysteroscopic surgery and to evaluate the surgical outcome. DESIGN:Retrospective clinical study (Canadian Task Force classification III). SETTING:Community hospital. PATIENTS:Twenty-six patients who underwent hysteroscopic surgery for treatment of endometrial polyps or submucous myomas <25 mm. INTERVENTIONS:Before hysteroscopic surgery, 13 patients (dienogest group) received 2 mg dienogest orally for 2 weeks, and 13 patients (GnRH group) received a gonadotropin-releasing hormone agonist subcutaneously 1 to 3 times every 4 weeks, and 4 of those received hormone therapy after surgery. Endometrial thickness, serum estradiol and progesterone concentrations, duration of surgery, weight of tissue removed, surgical field visualization, and time to resumption of spontaneous menstruation were recorded. MEASUREMENTS AND MAIN RESULTS:Endometrial thickness decreased from approximately 7.0 mm to 3.9 mm in the dienogest group. Duration of surgery and weight of tissue removed were similar between groups. The surgical field was clearly visualized in 12 patients in each group. Spontaneous menstruation resumed at approximately 22.0 days after hysteroscopic surgery in the dienogest group; in contrast, no resumption of spontaneous menstruation was observed within the first postoperative month in the GnRH group. No patients had perioperative complications, and none exhibited any residual tumor. CONCLUSION:Administration of dienogest for 2 weeks thinned the endometrium and yielded favorable surgical outcomes, similar to those with GnRH agonists. Administration of dienogest may be an effective and convenient treatment before hysteroscopy. 10.1016/j.jmig.2013.04.020
    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. Seo Jong-Wook,Lee Dong-Yun,Kim Sung Eun,Yoon Byung-Koo,Choi DooSeok European journal of obstetrics, gynecology, and reproductive biology OBJECTIVE:The 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. METHODS:This 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. RESULTS:Baseline 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. CONCLUSION:Our 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. 10.1016/j.ejogrb.2019.02.032
    Efficacy of dienogest in the treatment of symptomatic adenomyosis: a pilot study. Hirata Tetsuya,Izumi Gentaro,Takamura Masashi,Saito Ako,Nakazawa Akari,Harada Miyuki,Hirota Yasushi,Koga Kaori,Fujii Tomoyuki,Osuga Yutaka Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology Adenomyosis is a common disorder in premenopausal women that causes dysmenorrhea, pelvic pain and menorrhagia. Considering that adenomyosis is an estrogen-dependent disease, the medical treatment is based on this hormone. Effective and well-tolerated medical treatments for symptomatic adenomyosis are needed. Dienogest, an oral progestin, has been extensively investigated in the treatment of endometriosis. In this report, we present the results on the efficacy and safety of dienogest in the treatment of symptomatic adenomyosis. Seventeen patients with symptomatic adenomyosis were included in this study, of which 15 continued dienogest for up to 24 weeks. Dienogest significantly reduced adenomyosis-associated pelvic pain as well as serum CA-125 and CA19-9 levels. It also demonstrated a modest suppression of estradiol (>50 pg/ mL), which is consistent with the findings of other reports. During treatment, five patients experienced worsening anemia because of metrorrhagia, which is the most frequent adverse effect associated with dienogest. This report suggests that dienogest is an effective and well-tolerated therapy for symptomatic adenomyosis. 10.3109/09513590.2014.926882
    Medical treatment of ovarian endometriomas: a prospective evaluation of the effect of dienogest on ovarian reserve, cyst diameter, and associated pain. Muzii Ludovico,Galati Giulia,Di Tucci Chiara,Di Feliciantonio Mara,Perniola Giorgia,Di Donato Violante,Benedetti Panici Pierluigi,Vignali Michele Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology The aim of the present study was to evaluate the effect of medical treatment of ovarian endometriomas on cyst diameter, associated pain, and ovarian reserve as measured with antral follicle count (AFC) and anti-Mullerian hormone (AMH). In this prospective study, 32 patients with unilateral endometrioma associated with pelvic pain, underwent 6-month medical treatment with dienogest. Before treatment, and at the end of 6 months of treatment, patients underwent evaluation of endometrioma diameter and AFC at transvaginal ultrasonography, measurement of AMH, and evaluation of associated pain. Mean cyst diameter was 4.0 ± 1.3 cm at baseline, and 2.4 ± 1.2 cm after 6 months of treatment ( < .0001), for a reduction in diameter of 40% and a reduction in volume of 79%. Mean visual analog scale score at enrollment was 6.3 ± 2.0, with a significant improvement at 6 months (0.9 ± 1.0,  < .0001). AFC for the affected ovary improved from 4.2 ± 2.8 at baseline, to 8.6 ± 4.2 cm after 6 months (+105%;  < .0001). AMH did not change significantly from baseline (3.40 ± 2.32 ng/mL) to end of treatment (2.80 ± 1.90 ng/mL, -18%,  = .27). Medical treatment with dienogest significantly reduces endometrioma diameter and associated pain, whereas the ovarian reserve appears to be preserved, with a significant improvement of AFC and no significant change in AMH. 10.1080/09513590.2019.1640199
    Effect of Dienogest therapy on the size of the endometrioma. Vignali Michele,Belloni Gaia Maria,Pietropaolo Giuliana,Barbasetti Di Prun Allegra,Barbera Valeria,Angioni Stefano,Pino Ida Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology Studies have been published on the efficacy of Dienogest in the management of pain symptoms in endometriosis. Nonetheless, few data are available on the reducing effect on endometrioma's size. The aim of the study was to evaluate if Dienogest could determine significant changes in size, as well as in symptoms. In this prospective observational study, patients were enrolled with pain symptoms and at least one endometrioma diagnosed via TV-US. The volume of the endometrioma and pain symptoms was measured according to the LxDxWx0.5233 formula and VAS, respectively. Dienogest 2 mg was administered daily. Follow-up visits were scheduled after 6 and 12 months of treatment to assess changes in patients' symptoms and endometrioma's volume. Seventy patients were enrolled, 63 patients completed a 6-month treatment. The reduction of the mean volume after 6 months was 66.71%. Fifty-eight patients completed the 12 month-treatment. The reduction of the mean volume after 12 months was 76.19%. Dysmenorrhea showed a 74.05% reduction after 6 months and a 96.55% reduction after 12 months. Patients reported a reduction in dyspareunia and chronic pelvic pain of 42.71% and 48.91% after 6 months and 51.93% and 59.96% after 12 months, respectively. Dienogest leads to a statistically significant reduction of endometrioma's volume and pain symptoms. 10.1080/09513590.2020.1725965
    Dienogest treatment after ovarian endometrioma removal in infertile women prior to IVF. Muller Valeria,Kogan Igor,Yarmolinskaya Maria,Niauri Dariko,Gzgzyan Alexandr,Aylamazyan Edward Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology BACKGROUND:Severe forms of genital endometriosis are known to be associated with infertility and its subsequent treatment failure. Both gonadotropin-releasing hormone analogs (a-GnRH) and dienogest have been suggested as additional hormone therapy for patients with endometriomas. However, the result of hormonal suppression before an in vitro fertilization (IVF) cycle remains undetermined. MATERIALS AND METHODS:A prospective cohort study of 144 infertile women planning IVF after laparoscopic surgery of ovarian endometriomas was conducted at our department in 2012-2015. Patients were divided into three groups: group I (N = 38) with dienogest course, group II (N = 70) with a-GnRH group III (N = 70) without any hormonal therapy within 6 months preceding IVF. RESULTS:The study groups did not differ by removed endometriomas size and ovarian reserve indicators. The gonadotropin dose per Cycle was higher, while the number of retrieved oocytes was lower in group III patients (p < .001). In women with dienogest pretreatment, clinical pregnancy rate was 2.5 times (44.7% versus 16.7%, p = .012) and delivery rate - three times higher (36.8% versus 11.1%, p = .013) as compared with those from group III. CONCLUSIONS:The present study confirms the necessity of pre-cycle medical interventions in women with ovarian forms of endometriosis undergoing IVF. We suggest dienogest to be possibly more efficient treatment option for this kind of patients. 10.1080/09513590.2017.1415676
    Relief of uterine bleeding by cyclic administration of dienogest for endometriosis. Yanase Toru,Tsuneki Ikunosuke,Tamura Masaki,Kurabayashi Takumi Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology OBJECTIVE:This study assessed the relief of uterine bleeding and clinical symptoms during cyclic administration of dienogest for the treatment of endometriosis. METHODS:In total, 25 patients undergoing ovarian cyst enucleation and given dienogest participated in this study. Dienogest 2 mg/day was administered for 3 weeks, and the drug was then withdrawn for 1 week (cyclic administration of dienogest). This 4-week cycle was repeated six times. Patients' records were prospectively analyzed for the number of days on which any uterine bleeding occurred, as well as menstrual pain before and after the start of dienogest administration were evaluated with a view to using the data obtained herein as the basis. RESULTS:During the period of cyclic administration of dienogest, uterine bleeding occurred on 5.8 to 7.7 days per 4-week period on an average through cycles. Of uterine bleeding episodes, menstruation-like uterine bleeding was present in about 80% of patients. The visual analog scale (VAS) value for menstrual pain significantly decreased from 3.8 before dienogest administration after surgery to 1.5 at the completion of cycle 1, VAS remained low thereafter. CONCLUSION:These results raise the possibility that cyclic administration of dienogest may relieve lessen uterine bleeding, a major adverse event and menstrual pain. 10.3109/09513590.2014.943717
    Comparison of dienogest versus triptorelin acetate in premenopausal women with adenomyosis: a prospective clinical trial. Fawzy Muhammad,Mesbah Yasser Archives of gynecology and obstetrics PURPOSE:To compare the efficacy of the oral dienogest versus triptorelin acetate injection for treatment of premenopausal menorrhagia and pelvic pains in women with uterine adenomyosis. METHODS:A total of 41 patients with adenomyosis suffering from pelvic pains and menorrhagia were recruited. First group was managed with oral dienogest (2 mg/day, orally) while the second group received triptorelin acetate (3.75 mg/4 weeks, subcutaneous injection) for 16 weeks. Outpatient follow-up was undertaken after 8 weeks but mean values were calculated at baseline and after 16 weeks (end of treatment). RESULTS:A total of 41 women were allocated to treatment with dienogest (n = 22) or triptorelin acetate (n = 19); 19 (86.4 %) and 18 (94.7 %) % of the respective groups completed the trial. Significant reductions in pelvic pains after 16 weeks treatment were obtained in both groups demonstrating the equivalence of dienogest relative to triptorelin acetate. Triptorelin acetate was more effective in controlling of menorrhagia and reduction of uterine volume. CONCLUSIONS:Dienogest may be a valuable alternative to depot triptorelin acetate for treatment of premenopausal pelvic pains in women with uterine adenomyosis. 10.1007/s00404-015-3755-5
    Gonadotropin-releasing hormone agonist with add-back treatment is as effective and tolerable as dienogest in preventing pain recurrence after laparoscopic surgery for endometriosis. Lee Dong-Yun,Lee Jee-Yeon,Seo Jong-Wook,Yoon Byung-Koo,Choi DooSeok Archives of gynecology and obstetrics PURPOSE:This study was performed to compare the efficacy and tolerability of GnRH agonist with add-back therapy versus dienogest treatment for preventing pelvic pain recurrence after laparoscopic surgery for endometriosis. METHODS:Sixty-four reproductive-aged women who underwent laparoscopic surgery for endometriosis received post-operative medical treatment with either GnRH agonist plus 17β-estradiol and norethisterone acetate (n = 28) or dienogest (n = 36) for 6 months. The pre- to post-treatment changes in pain were assessed using a visual analogue scale, and changes in quality-of-life and menopausal symptoms were measured by questionnaire. RESULTS:Visual analogue scale pain score decreased significantly for both treatments with no significant differences between groups. Neither physical, psychological, social, and environmental components of quality-of-life nor menopausal rating scale score were significantly different between the two groups. Bone mineral density at the lumbar spine declined significantly in both treatment groups (-2.5 % for GnRH agonist plus add-back and -2.3 % for dienogest), with no significant difference between the two groups. CONCLUSION:GnRH agonist and add-back therapy using 17β-estradiol and norethisterone acetate are as effective and tolerable as dienogest for the prevention of pelvic pain recurrence after laparoscopic surgery for endometriosis. 10.1007/s00404-016-4184-9
    Is dienogest the best medical treatment for ovarian endometriomas? Results of a multicentric case control study. Angioni Stefano,Pontis Alessandro,Malune Maria E,Cela Vito,Luisi Stefano,Litta Pietro,Vignali Michele,Nappi Luigi Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology Ovarian endometriomas are common manifestations of endometriosis. Surgical excision has been shown to potentially decrease ovarian reserves. In this prospective study, we included 81 patients with ovarian endometriosis. 40 were treated with 2 mg of dienogest daily (DNG) and 41 were treated with cyclic oral estro-progestins (ethinyl estradiol 30 mcg [EE] plus dienogest 2 mg) (DNG + EE). Aim of the study was the effect of the treatment on the size of the endometriotic cysts. Further, in the symptomatic patients, follow-up included an evaluation of chronic pain before and during treatment. Both treatments were able to significantly decrease the pain in symptomatic patients with no statistical differences. The mean visual analog scale score at enrollment was 65 ± 14 and 70 ± 18, and there was significant improvement (19 ± 15,  < .001, DNG; 18 ± 12,  < .001, DNG + EE). The size of the endometrioma cysts were significantly reduced in the DNG group. The mean cyst diameter was 52 ± 22 mm at baseline and 32 ± 12 mm after six months of treatment ( < .001), yielding a 75% volume reduction in DNG group. The decrease in the size of endometrioma cysts observed in the women treated with only progestin could be noteworthy, as it may reduce the negative impacts on the affected ovary and avoid surgery. 10.1080/09513590.2019.1640674
    Short-term histopathological effects of dienogest therapy on ovarian endometriomas: in vivo, nonrandomized, controlled trial. Mabrouk Mohamed,Paradisi Roberto,Arena Alessandro,Del Forno Simona,Matteucci Carlotta,Zannoni Letizia,Caprara Giacomo,Seracchioli Renato Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology Ovarian endometriosis is a common gynecological disorder. To date, progestins are recommended as the first-line medical treatment for symptomatic ovarian endometriosis. The aim of this study was to evaluate the main histopathological effects of short-term dienogest therapy in patients with ovarian endometriomas scheduled for surgery. A prospective, nonrandomized controlled trial, including 70 symptomatic women with single ovarian endometriotic cyst (diameter between 30-50 mm) was conducted. Women scheduled for surgery were divided into two groups, depending on the treatment established at enrollment: 36 women received progestin therapy with dienogest (P group) and 34 women received no therapy (C group). At histopathological examination necrosis, inflammation, decidualization, glandular atrophy and angiogenesis were blindly evaluated. At tissue level, decidualization was significantly more frequent in P group compared to C group (p = .001). A nonsignificant tendency (p = .29) towards a slight decreased inflammation in P group was found. No significant differences were observed between the two groups in terms of necrosis, glandular atrophy and angiogenesis. The study suggests that high decidualization rate and the tendency to reduced inflammatory reaction in the short-term administration of dienogest might contribute to its therapeutic efficacy. 10.1080/09513590.2017.1405932
    Efficacy and safety of dienogest in patients with endometriosis: A single-center observational study over 12 months. Park So Yun,Kim Sung Hoon,Chae Hee Dong,Kim Chung-Hoon,Kang Byung Moon Clinical and experimental reproductive medicine OBJECTIVE:To evaluate the efficacy and safety of dienogest treatment in patients who had received dienogest for 12 months or more to treat endometriosis. METHODS:We analyzed the clinical data of 188 women with endometriosis who had been treated with 2 mg of dienogest once a day for 12 months or more at a single institute. We evaluated changes in endometriosis-associated pain and endometrioma size, recurrence rate, and adverse events following dienogest administration. Bone mineral density (BMD) was measured in patients who were prescribed dienogest for more than 18 months. RESULTS:Pain was significantly reduced at 12 months after dienogest medication. In those treated with dienogest due to recurrent endometrioma, the size of the endometrioma was significantly decreased at the 12-month and 18-month follow-ups. We found only one case of sonographic recurrence during dienogest administration among those who were treated postoperatively to prevent recurrence (1 of 114, 0.9%). The most common adverse drug reaction was uterine bleeding (3.2%), and other adverse events were generally tolerable and associated with low discontinuation rates (5.2%). Among the 50 patients in whom BMD was measured, 10 patients (20%) had a Z-score below the expected range for age. CONCLUSION:The administration of dienogest for a year or more seems to be highly effective in preventing recurrence after surgery, reducing endometriosis-associated pain, and decreasing the size of recurrent endometrioma, with a favorable safety and tolerability profile. However, BMD should be checked in patients on long-term medication due to possible bone loss in some women. 10.5653/cerm.2016.43.4.215
    Use of dienogest in endometriosis: a narrative literature review and expert commentary. Murji Ally,Biberoğlu Kutay,Leng Jinhua,Mueller Michael D,Römer Thomas,Vignali Michele,Yarmolinskaya Maria Current medical research and opinion Endometriosis affects up to 10% of women of reproductive age, and the main goal of treatment is to relieve symptoms. Progestins have been the mainstay of endometriosis suppression, of which dienogest has become an important option in many parts of the world. This is an expert literature review, with recommendations on the use of dienogest in the context of various clinical considerations when treating endometriosis. A search of PubMed was conducted for papers published between 2007 and 2019 on the use of dienogest in endometriosis. Experts reviewed these and included those they considered most relevant in clinical practice, according to their own clinical experience.: Evidence regarding the long-term use (>15 months) of dienogest for the management of endometriosis is presented, with experts concluding that the efficacy of dienogest should be assessed primarily on its impact on pain and quality of life. Fertility preservation, the option to avoid or delay surgery, and managing bleeding irregularities that can occur with this treatment are also considered. Counseling women on potential bleeding risks before starting treatment may be helpful, and evidence suggests that few women discontinue treatment for this reason, with the benefits of treatment outweighing any impact of bleeding irregularities. Overall, the evidence demonstrates that dienogest offers an effective and tolerable alternative or adjunct to surgery and provides many advantages over combined hormonal contraceptives for the treatment of endometriosis. It is important that treatment guidelines are followed and care is tailored to the woman's individual needs and desires. 10.1080/03007995.2020.1744120
    Efficacy of dienogest in improving pain in women with endometriosis: a 12-month single-center experience. Maiorana A,Incandela Domenico,Parazzini F,Alio W,Mercurio A,Giambanco L,Alio L Archives of gynecology and obstetrics PURPOSE:Dienogest has recently been marketed as a medical treatment for endometriosis. Given the recent introduction on the market of Dienogest, little data are available regarding its effectiveness in routine clinical practice. METHODS:The study is an observational, single-center, cohort study. Eligible was women with a surgical diagnosis of endometriosis dating back <24 months or a clinical/instrumental diagnosis of endometriosis and endometriosis-associated pelvic pain score of at least 40 mm on a 100-mm visual analog scale (VAS) at start of treatment and who had been taking Dienogest 2 mg once daily treatment at the time of study entry for no more than 30 days, consecutively observed between September 2013 to September 2014. In accordance with routine practice, women came back for clinical assessment and evaluation of pain after 1 (V1), 3 (V2), and 12 (V3) months. RESULTS:A total of 132 women were enrolled in the study. A total of 21 of the enrolled patients were released from the study during follow-up due to adverse effects. The mean pelvic pain VAS score at baseline was 8.9 (SD 1.3). The corresponding values were 6.7 (SD 3.2) and 5.7 (SD 3.7) for dyspareunia and dyschezia. The mean VAS scores progressively and significantly decreased to 0.9 (SD 1.6) for pelvic pain, 1.4 (SD 2.1) for dyspareunia and 0.2 (SD 0.9) for dyschezia, respectively, 12 months after start of treatment. CONCLUSION:This study confirms that in routine clinical practice, Dienogest 2 mg is an effective and well-tolerated treatment for endometriosis-related pain in women with endometriosis. 10.1007/s00404-017-4442-5
    Postoperative administration of dienogest for suppressing recurrence of disease and relieving pain in subjects with ovarian endometriomas. Adachi Kazushige,Takahashi Kayo,Nakamura Koji,Otake Akiko,Sasamoto Naoko,Miyoshi Yukari,Shioji Mitsunori,Yamamoto Yoshimitsu,Fujitani Mayumi,Wakimoto Akinori,Tokuhira Atsushi,Kobayashi Eiji,Yoshimura Akihiko,Sawada Kenjiro,Kimura Tadashi Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology To assess the effect of dienogest on recurrence of ovarian endometriomas and severity of pain after laparoscopic surgery, a retrospective study of 81 patients was performed at three institutions in Osaka, Japan. Patients had a six-month minimum follow-up after laparoscopic surgery for ovarian endometriomas performed between June 2012 and August 2014. Patients who chose to receive 2 mg dienogest daily and those who were managed expectantly postoperatively were included. Recurrence was defined as the presence of endometriomas of more than 2 cm. A visual analog scale (VAS) was used to score the intensity of pelvic pain. The cumulative recurrence rate and absolute VAS score changes between the baseline and at 6, 12, 18 and 24 months after the start of administration were evaluated in both groups. The recurrence rate was 16.5% and 24.0% in the expectant management group at 12 and 24 months, respectively. No recurrences occurred in the dienogest treatment group. The rate of VAS score reduction was significantly higher in the dienogest than in the expectant management group. Dienogest is effective on the recurrence of ovarian endometrioma and relieving pelvic pain after laparoscopic surgery. 10.3109/09513590.2016.1147547
    Dienogest 2 mg Daily in the Treatment of Adolescents with Clinically Suspected Endometriosis: The VISanne Study to Assess Safety in ADOlescents. Ebert Andreas D,Dong Liying,Merz Martin,Kirsch Bodo,Francuski Maja,Böttcher Bettina,Roman Horace,Suvitie Pia,Hlavackova Olga,Gude Kerstin,Seitz Christian Journal of pediatric and adolescent gynecology STUDY OBJECTIVE:To study the safety and efficacy of dienogest 2 mg in adolescents with suspected endometriosis. DESIGN:A 52-week, open-label, single-arm study. SETTING:In 21 study centers, in 6 European countries. PARTICIPANTS:Adolescents aged 12 to younger than 18 years with clinically suspected or laparoscopically confirmed endometriosis. INTERVENTIONS:Dienogest 2 mg once daily. MAIN OUTCOME MEASURES:The primary end point was relative change in lumbar spine (L2-L4) bone mineral density (BMD) measured using dual-energy x-ray absorptiometry. A key secondary end point was change in endometriosis-associated pain assessed using a visual analogue scale. RESULTS:Of 120 patients screened, 111 comprised the full-analysis set (ie, patients who took ≥1 dose of study drug and had ≥1 post-treatment observation) and 97 (87.4%) completed the study. Mean lumbar BMD at baseline was 1.1046 (SD, 0.1550) g/cm. At the end of dienogest treatment (EOT; defined as at 52 weeks or premature study discontinuation), mean relative change in BMD from baseline was -1.2% (SD, 2.3%; n = 103). Follow-up measurement 6 months after EOT in the subgroup with decreased BMD at EOT (n = 60) showed partial recovery in lumbar BMD (mean change from baseline: -2.3% at EOT, -0.6% 6 months after EOT). Mean endometriosis-associated pain score was 64.3 (SD, 19.1) mm at baseline and decreased to 9.0 (SD, 13.9) mm by week 48. CONCLUSION:In adolescents with suspected endometriosis, dienogest 2 mg for 52 weeks was associated with a decrease in lumbar BMD, followed by partial recovery after treatment discontinuation. Endometriosis-associated pain was substantially reduced during treatment. Because bone accretion is critical during adolescence, results of the VISanne study to assess safety in ADOlescents (VISADO) study highlights the need for tailored treatment in this population, taking into account the expected efficacy on endometriosis-associated pain and an individual's risk factors for osteoporosis. 10.1016/j.jpag.2017.01.014
    Norethindrone acetate or dienogest for the treatment of symptomatic endometriosis: a before and after study. Vercellini Paolo,Bracco Benedetta,Mosconi Paola,Roberto Anna,Alberico Daniela,Dhouha Dridi,Somigliana Edgardo Fertility and sterility OBJECTIVE:To assess the proportion of patients satisfied with their treatment before and after a systematic change from norethindrone acetate to dienogest as the first-line progestin for symptomatic endometriosis. DESIGN:Before and after study. SETTING:Academic department. PATIENT(S):The last 90 new consecutive endometriosis patients in whom norethindrone acetate was used, and the first 90 new consecutive endometriosis patients in whom dienogest was used. INTERVENTION(S):Norethindrone acetate at the oral dose of 2.5 mg once a day until June 6, 2013, then dienogest at the oral dose of 2 mg once a day thereafter. MAIN OUTCOME MEASURE(S):Degree of satisfaction with treatment after 6 months of progestin therapy and assessment of any variations in pain symptoms, psychological status, sexual function, or health-related quality of life associated with the introduction of dienogest. RESULT(S):The proportion of satisfied plus very satisfied women after 6 months of treatment was 71% in the "before" period (norethindrone acetate) and 72% in the "after" period (dienogest). The implementation of dienogest was not associated with statistically significant ameliorations in overall pain relief, psychological status, sexual functioning, or health-related quality of life. Treatment was well tolerated by 58% of norethindrone acetate users compared with 80% of dienogest users. After dienogest implementation, the absolute risk reduction in the occurrence of any side effect was 13.9% (95% confidence interval, 0.8%-28.6%). CONCLUSION(S):Considering the large difference in the cost of the two drugs, dienogest should be suggested selectively in women who do not tolerate norethindrone acetate. 10.1016/j.fertnstert.2015.11.016
    Clinical experience of long-term use of dienogest after surgery for ovarian endometrioma. Chandra Anjali,Rho A Mi,Jeong Kyungah,Yu Taeri,Jeon Ji Hyun,Park So Yun,Lee Sa Ra,Moon Hye-Sung,Chung Hye Won Obstetrics & gynecology science Objective:Endometriosis is a common and recurring gynecologic disease which have afflicting females of reproductive age. We investigated the efficacy of long-term, post-operative use of dienogest for ovarian endometrioma. Methods:We studied 203 patients who had undergone laparoscopic or robotic surgery for ovarian endometrioma, and were administrated dienogest 2 mg/day beginning in July of 2013, and continuing. We evaluated side effects of dienogest and ultrasonography was performed every 6 months to detect potential recurrence of endometrioma (2 cm) in these post-surgical patients. Results:The follow-up observation periods were 30.2±20.9 months from surgery. The mean age was 34.1±7.2 years old. The mean diameter of pre-operative endometrioma was 5.6±3.0 cm. One hundred eighty-two (89.7%) women received dienogest continuously for 12.0±7.1 months. Of the subjects, 21 (10.3%) patients discontinued dienogest at 2.4±1.0 months. The most common side effect when dienogest was discontinued was abnormal uterine bleeding. The occurrence rate of vaginal bleeding was 15.8%, a number which did not differ significantly in patients with/without post-operative gonadotropin releasing hormone agonist administration. The other side effects were gastrointestinal trouble including constipation, acne, headache, depression, hot flush, weight gain, and edema. However, no serious adverse events or side effects were documented and recurrent endometriomas were diagnosed in 3 patients (1.5%). Conclusion:The data indicates that dienogest was both tolerable and safe for long-term use as prophylaxis in an effort to obviate the recurrence of ovarian endometrioma post-operatively, as well as potential need for surgical re-intervention. 10.5468/ogs.2018.61.1.111
    Dienogest as preoperative treatment of submucous myomas for hysteroscopic surgery: a prospective, randomized study. Laganà Antonio Simone,Giacobbe Valentina,Triolo Onofrio,Granese Roberta,Ban Frangež Helena,Vrtačnik-Bokal Eda,Ietto Chiara,Palmara Vittorio Italo Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology The aim of this single-center, prospective, randomized, parallel-group study was to compare Dienogest and Danazol as endometrial preparation in patients who have to undergo hysteroscopic surgery for submucous myomas. We enrolled 80 consecutive eligible patients, in reproductive age, affected by submucous myomas. Pre- and posttreatment characterization of endometrium was performed by hysteroscopic visual observation and histologic confirmation. The enrolled patients were randomly assigned to two groups: 40 were treated with 2 mg of Dienogest/die, 40 with 100 mg of Danazol/die, both orally for 5 weeks, starting on day 1 of menstruation. Posttreatment comparison of endometrial patterns showed a significant more marked effect of Dienogest, respect to Danazol, in atrophying endometrium ("normotrophic non-responders" versus "hypotrophic"-"atrophic", p = 0.028). Intraoperative data showed no significant difference between the two groups for cervical dilatation time (p = 0.326), while in the Dienogest group, we found a significant reduction of operative time (p = 0.001), infusion volume (p = 0.001), and severity of bleeding (p = 0.042). Moreover, Dienogest caused less side effects (p = 0.008). According to our data analysis, Dienogest, respect to Danazol, is more effective for the preparation of the endometrium in patients who have to undergo hysteroscopic surgery for submucous myomas, and causes less side effects. 10.3109/09513590.2015.1128409
    Dienogest and deep infiltrating endometriosis: The remission of symptoms is not related to endometriosis nodule remission. Leonardo-Pinto Joao Paulo,Benetti-Pinto Cristina Laguna,Cursino Kleber,Yela Daniela Angerame European journal of obstetrics, gynecology, and reproductive biology OBJECTIVE:To evaluate the effectiveness of dienogest in controlling pain caused by deep infiltrating endometriosis (DIE), its influence on the quality of live (QoL) of women affected by the disease, and the effect of the drug on the volume of endometriotic lesions. STUDY DESIGN:A prospective cohort study including 30 women with a sonographic diagnosis of DIE (intestinal and posterior fornix) treated with dienogest 2mg per day for 12 months. We evaluated the pain symptoms and the volume of the intestinal and posterior fornix lesions before and after 12 months of use of dienogest. To perform the statistical analysis, we used the Wilcoxon signed-rank test, and the relationship between the data was tested using the Spearman correlation coefficient. RESULTS:Women were on average 36.13±6.24years old. Pain symptoms most commonly reported were dyspareunia (83.3%), dysmenorrhea (73.3%), and pelvic pain (66.7%). After 12 months of treatment with dienogest, there was significant improvement of various symptoms (dyspareunia p=0.0093, dysmenorrhea p<0.0001; pelvic pain p=0.0007; and bowel pain p<0.0001), without a reduction in the volume of endometriotic nodules. There were significant improvements in the parameters that comprise the QoL (physical p<0.0001; p=0.0007 psychological) and the self-assessment of QoL (p=0.0069) and health (p=0.0001). CONCLUSION:Dienogest is an effective medication to control symptoms of pain related to DIE, even without reducing the volume of DIE nodules. 10.1016/j.ejogrb.2017.02.015
    Dienogest compared with gonadotropin-releasing hormone agonist after conservative surgery for endometriosis. Takaesu Yotaro,Nishi Hirotaka,Kojima Junya,Sasaki Toru,Nagamitsu Yuzo,Kato Rina,Isaka Keiichi The journal of obstetrics and gynaecology research AIM:Although there are various hormone therapies, including gonadotropin-releasing hormone agonist, danazol, levonorgestrel-releasing intrauterine system, dienogest, and low-dose estrogen progestin, no consensus opinion has been reached in terms of which medication should be used and for how long it should be administered. We aimed to determine whether dienogest or goserelin is the better postoperative therapy to prevent recurrence of endometriosis. METHODS:A prospective cohort randomized study were conducted, including 198 patients diagnosed as having endometriosis. A total of 111 patients were randomly assigned into two groups: the dienogest-administered group (n = 56) and the goserelin-administered group (n = 55). Patients were followed for 24 months after laparoscopic surgery. Those who gave consent but desired no postoperative therapy were assigned to the non-treatment group (n = 79). Recurrence, side-effects, degrees of menstrual pain and chronic pelvic pain measured by the Visual Analogue Scale were compared among the three groups: the dienogest, goserelin, and non-treatment groups. RESULTS:No significant difference was observed in the postoperative recurrence rate between the dienogest and goserelin groups. No significant difference was found in the recurrence rate between the goserelin group and non-treatment group; however, a significant difference was found in the recurrence rate between the dienogest group and the non-treatment group (P = 0.027). Menstrual pain and chronic pelvic pain were significantly improved in both treatment groups. Side-effects were markedly observed in the goserelin group as compared with the dienogest group. CONCLUSION:Dienogest is available for prolonged administration of more than 6 months, so it is more useful than goserelin, which is available only for short-term administration. 10.1111/jog.13023
    Dienogest and the Risk of Endometriosis Recurrence Following Surgery: A Systematic Review and Meta-analysis. Zakhari Andrew,Edwards Darl,Ryu Michelle,Matelski John J,Bougie Olga,Murji Ally Journal of minimally invasive gynecology STUDY OBJECTIVE:To determine whether dienogest therapy after endometriosis surgery reduces the risk of endometriosis recurrence compared with expectant management. DATA SOURCES:Ovid MEDLINE, Ovid EMBASE, PubMed, Cochrane Central Register of Controlled Trials, Web of Science, LILACS, clinicaltrials.gov, and International Standard Randomized Controlled Trial Number Registry were searched from inception to March 2019 for observational and randomized controlled trials. METHODS OF STUDY SELECTION:The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. Medical Subject Heading terms and keywords such as "dienogest," "endometriosis," and "recurrence" were used to identify relevant studies. TABULATION, INTEGRATION, AND RESULTS:The search yielded 328 studies, 10 of which were eligible for inclusion, representing 1184 patients treated with dienogest and 846 expectantly managed controls. Among these studies, 9 looked exclusively at endometrioma recurrence, whereas 1 used reappearance of symptoms as evidence of disease recurrence. Data on both incidence of and time to recurrence of endometriosis were extracted. The incidence rate of endometriosis recurrence in patients treated with dienogest was 2 per 100 women over a mean follow-up of 29 months (95% confidence interval [CI], 1.43-3.11) versus 29 per 100 women managed expectantly over a mean follow-up of 36 months (95% CI, 25.66-31.74). The likelihood of recurrence was significantly reduced with postoperative dienogest (log odds -1.96, CI, -2.53 to -1.38, p <.001). CONCLUSION:Patients receiving dienogest after conservative surgery for endometriosis had significantly lower risk of postoperative disease recurrence than those who were expectantly managed. 10.1016/j.jmig.2020.05.007
    Efficacy of dienogest treatment of clinical symptoms of rectovaginal endometriosis. Papíková Z,Hudeček R,Ventruba P,Szypulová M Ceska gynekologie OBJECTIVE:The aim of this prospective, unicentric, cohort study was to evaluate the effect of dienogest use in the therapy of symptomatic endometriosis of rectovaginal septum in patients of fertile age. STUDY DESIGN:Prospective, unicentric, cohort study. SETTING:Department of Obstetrics and Gynaecology, Brno University Hospital and Masaryk University Medical School, Brno. MATERIAL AND METHODS:Prospective analysis of the group of 32 patients in reproductive age who have previously been diagnosed with endometriosis of rectovaginal septum. These patients were treated conservatively with dienogest 2 mg per day during a 24-week period. Through questionnaires and clinical assessment, we have studied the presence of symptoms like dyspareunia, diffuse pelvic pain, Biberoglu-Behrman(B-B) score assessment and subjective pain perception using Visual Analogue Scale (VAS) of pain. Data were collected at the beginning of therapy, after 4, 12 and 24 weeks of dienogest use. RESULTS:Continual use of dienogest during the 24-week period diminishes symptoms of dyspareunia by 62% (p.
    Dienogest Versus Leuprolide Acetate for Recurrent Pelvic Pain Following Laparoscopic Treatment of Endometriosis. Abdou Ahmed Mahmoud,Ammar Islam Mohamed Magdi,Alnemr Amr Abd Almohsen,Abdelrhman Amr Ahmed Journal of obstetrics and gynaecology of India Objective: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. Design:Prospective randomized trial. Setting:Zagazig University hospitals, Egypt. Patients:Two hundred and forty-two patients with recurrent pelvic pain following laparoscopic surgery for endometriosis. Intervention:Dienogest (2 mg/day, orally) or depot LA (3.75 mg/4 weeks, intramuscularly) for 12 weeks. Main Outcome Measures:A visual analogue scale was used to test the intensity of pain before and after the end of treatment. Results: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 ± 3.08 mm, respectively) and in LA group (26.2 ± 3.01, 19.5 ± 3.01 and 17.9 ± 2.9 mm, 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). Conclusion: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. 10.1007/s13224-018-1119-3
    Combination of microwave endometrial ablation and postoperative dienogest administration is effective for treating symptomatic adenomyosis. Ota Kuniaki,Takahashi Toshifumi,Shiraishi Satoru,Mizunuma Hideki The journal of obstetrics and gynaecology research AIM:Menorrhagia and dysmenorrhea are common symptoms. Uterine adenomyosis is one of the causes of menorrhagia and dysmenorrhea. These symptoms often decrease the quality of life in women. Microwave endometrial ablation (MEA) is a recently developed procedure that enables endometrial ablation. Dienogest has long been used to suppress endometrium development and reduce adenomyosis-related dysmenorrhea. However, some cases could be resistant to dienogest. In this study, we evaluated the efficacy of a combination of MEA and postoperative dienogest in reducing adenomyosis-related dysmenorrhea and menorrhagia. METHODS:Ten patients with hormone treatment-resistant symptomatic adenomyosis underwent MEA and were administered oral dienogest after the procedure. The primary endpoints were reduction in pain recurrence and anemia. The secondary endpoint was a change in the adenomyosis lesion and its symptomatic recurrence. RESULTS:Statistically significant improvements were seen in the visual analog scale score and hemoglobin levels in women post-treatment. The difference in myometrial thickness pre- and post-MEA was statistically significant. There were no cases of symptomatic recurrence. CONCLUSION:The combination of MEA and postoperative dienogest is useful for treating uterine adenomyosis with menorrhagia and dysmenorrhea. 10.1111/jog.13720
    Dienogest for Treatment of Endometriosis in Chinese Women: A Placebo-Controlled, Randomized, Double-Blind Phase 3 Study. Lang Jinghe,Yu Qi,Zhang Shulan,Li Huajun,Gude Kerstin,von Ludwig Christiane,Ren Xiaowei,Dong Liying Journal of women's health (2002) BACKGROUND:Dienogest is a progestin with demonstrated efficacy in the treatment of endometriosis in European women. The objective of this study was to evaluate the efficacy and safety of dienogest in Chinese women. PATIENTS AND METHODS:This 24-week, randomized, double-blind, placebo-controlled multicenter (n = 23) study evaluated the efficacy and safety of 2 mg dienogest once daily in 255 Chinese women aged 18-45 years with laparoscopically diagnosed endometriosis and an endometriosis-associated pelvic pain (EAPP) score ≥30 mm on a 0-100 mm visual analog scale. The primary efficacy variable was absolute change in EAPP from baseline to week 24. Secondary efficacy variables included proportions of responders and intake of supportive analgesic medication. Safety variables included adverse events (AEs), laboratory parameters, and bleeding patterns. Bone mineral density (BMD) was evaluated in a subset of 140 women. RESULTS:After 24 weeks of treatment, the difference between treatment arms for mean reduction in EAPP was statistically significant in favor of dienogest (-24.54 mm; 95% CI -29.93 to -19.15; p < 0.0001). Secondary efficacy analyses supported the significant superiority of dienogest over placebo. Dienogest was well tolerated, with few AEs associated with therapy. Dienogest had no effect on BMD levels after 24 weeks of treatment. CONCLUSIONS:Dienogest 2 mg once daily for 24 weeks was superior to placebo in reducing EAPP and was safe and well tolerated in Chinese women with endometriosis. The results are consistent with studies previously conducted in European women. 10.1089/jwh.2017.6399
    Effectiveness of dienogest in improving quality of life in Asian women with endometriosis (ENVISIOeN): interim results from a prospective cohort study under real-life clinical practice. Techatraisak Kitirat,Hestiantoro Andon,Ruey Soon,Banal-Silao Maria Jesusa,Kim Mee-Ran,Seong Seok Ju,Thaufik Syarief,Ahlers Christiane,Shin So Young,Lee Byung Seok BMC women's health BACKGROUND:Dienogest has been shown to substantially improve endometriosis-associated symptoms such as debilitating chronic pelvic pain, and in turn, health-related quality of life (HRQoL). To date, there is no data on patient-reported outcomes reflecting the real-world practice in Asia where endometriosis is a relevant health, social and economic burden. This non-interventional, multi-center, prospective study aims to investigate the influence of dienogest on HRQoL. METHODS:Asian women received dienogest (2 mg/daily) and were followed for 24 months. The effectiveness of dienogest to improve HRQoL and endometriosis-associated pelvic pain (EAPP) was assessed by patient-reported outcomes. HRQoL, especially the "pain" domain as primary endpoint, was evaluated with the Endometriosis Health Profile-30 (EHP-30) questionnaire. The numeric rating scale served to determine changes in the severity of EAPP. Within the presented interim analysis (data cut-off: 2017-11-27), the mean changes in EHP-30 and EAPP scores from baseline to 6 months upon availability of the data were evaluated. Treatment-emergent adverse events (TEAEs) and bleeding profiles were documented. RESULTS:Dienogest therapy decreased EHP-30 scores in all assessed domains (score 0-100, lower scores indicate better HRQoL). Primarily, the "pain" domain was improved in 78.4% of patients. EAPP was reduced (score 0-10, lower scores reflect less pain), highlighted by a mean reduction of the pain score by - 4.5 points. Patients with a higher EAPP score at baseline had an increased response to dienogest (- 6.2 points mean change) compared to patients with low baseline EAPP severity (- 1.4 points mean change). Both surgically and clinically diagnosed patients described comparable pain reduction, as well as women with or without prior treatment. Drug-related TEAEs were documented for 31.5% of patients, with amenorrhoea (5.9%) and metrorrhagia (5.1%) being the most common events. The bleeding pattern was changed upon dienogest, characterized by decreased normal bleeding (84.2 to 28.8%) and increased amenorrhea (3.2 to 42.9%) at 6 months. CONCLUSION:The data indicate an amelioration of HRQoL and EAPP upon dienogest therapy. No new safety signals were observed. Therefore, its use as first-line therapy for long-term management of debilitating and chronic endometriosis-associated pain represents an interesting option that remains to be further investigated. TRIAL REGISTRATION:Name of registry: Clinical Trials Clinicaltrials.gov registration number: NCT02425462 Registration date: 2015-04-24. Registration timing: prospective. 10.1186/s12905-019-0758-6
    Safety of Dienogest and Other Hormonal Treatments for Endometriosis in Real-World Clinical Practice (VIPOS): A Large Noninterventional Study. Heinemann Klaas,Imthurn Bruno,Marions Lena,Gerlinger Christoph,Becker Kerstin,Moehner Sabine,Faustmann Thomas Advances in therapy INTRODUCTION:Endometriosis is a common gynecologic disease associated with a significant burden on women's health and healthcare systems. Currently approved hormonal treatments for endometriosis can be effective in controlling symptoms, but may have clinically relevant side effects that limit their long-term use. Dienogest 2 mg (Visanne; Bayer AG, Berlin, Germany) is a 19-nortestosterone derivative that significantly reduces menstrual bleeding, dysmenorrhea, premenstrual pain, dyspareunia, and pelvic pain in women with endometriosis. Although dienogest 2 mg has demonstrated efficacy in clinical trials, data regarding long-term and real-world use are limited. METHODS:To our knowledge, the Visanne Post-approval Observational Study (VIPOS) is the largest real-world, noninterventional study performed examining the safety of dienogest and other hormonal treatments for the management of endometriosis in routine clinical practice. Patients self-reported medical and gynecologic history and symptoms and treatment information. Primary clinical outcomes were clinically validated and subject to independent blinded adjudication. Loss to follow-up was minimized through active contact with participating women at 6 months post-enrollment and annually thereafter to ensure almost all clinically relevant outcomes were captured. PLANNED OUTCOMES:VIPOS planned to enroll approximately 25,000 women initiating a new treatment for endometriosis, including those prescribed dienogest 2 mg/day and other hormonal medications for endometriosis (approved or nonapproved), from approximately 1000 centers in six European countries. The main clinical outcomes of interest for follow-up are anemia requiring medical intervention, de novo or clinically worsening depression, and treatment-failure patterns that result in drug discontinuation. Additional analyses will characterize the baseline risk factors of medically managed patients with endometriosis and assess treatment utilization patterns. VIPOS was designed to provide real-world information on endometriosis treatment and associated clinical outcomes, while not affecting the prescribing physician's decisions or the classification of patient diagnoses. TRIAL REGISTRATION:European Union Electronic Register of Post-Authorisation Studies (EU PAS) no. 1613, Clinicaltrials.gov: NCT01266421. 10.1007/s12325-020-01331-z
    Long-term dienogest administration in patients with symptomatic adenomyosis. Neriishi Kazuaki,Hirata Tetsuya,Fukuda Shinya,Izumi Gentaro,Nakazawa Akari,Yamamoto Naoko,Harada Miyuki,Hirota Yaushi,Koga Kaori,Wada-Hiraike Osamu,Fujii Tomoyuki,Osuga Yutaka The journal of obstetrics and gynaecology research AIM:Adenomyosis is a common gynecological disorder that causes dysmenorrhea, hypermenorrhea and metrorrhagia. Previously, we reported that 24 weeks of dienogest treatment is highly effective for pain in symptomatic adenomyosis. Up to present, there is no report that describes treatment of adenomyosis with long-term dienogest administration for more than 2 years. In this retrospective cohort study, we investigated the course of long-term dienogest treatment in patients with symptomatic adenomyosis. METHODS:This is a retrospective cohort study. Dienogest was continuously administered at a dose of 2 mg daily for patients with symptomatic adenomyosis. The outcome of long-term administration of dienogest was investigated, and the characteristics of patients were compared between discontinued cases and long-term administration cases. RESULTS:Two patients were excluded from this study because of transfer to another hospital or discontinuation due to infertility treatment. Twelve of 18 patients (66.7%) received dienogest until menopause or for a period of >80 months. Four cases (22.2%) discontinued dienogest treatment because of severe metrorrhagia. In the discontinued cases because of severe metrorrhagia, the pain score for dysmenorrhea and serum CA125 level at baseline significantly elevated, and the hemoglobin level at baseline and the frequency of type 2 adenomyosis significantly decreased, compared to those with long-term use. Moreover, long-term dienogest use did not decrease the serum estradiol level. CONCLUSION:Our report suggests that dienogest is tolerable for long-term use until menopause and can be an alternative treatment option in some patients, especially those with type 2 adenomyosis, to avoid hysterectomy. 10.1111/jog.13674
    Long-term treatment of endometriosis with dienogest: retrospective analysis of efficacy and safety in clinical practice. Römer Thomas Archives of gynecology and obstetrics PURPOSE:Endometriosis is a debilitating disease with high recurrence rates requiring long-term management. Progestins such as dienogest are used empirically when first symptoms occur and post-surgery to reduce recurrence. This retrospective, practice-based study assessed the efficacy and safety of dienogest in women with endometriosis treated for at least 60 months. METHODS:37 women (age 39 ± 8 years) with laparoscopically diagnosed endometriosis received dienogest 2 mg orally once daily. Endometriosis-associated pelvic pain (EAPP) was measured on a 0-100 mm visual analog scale at baseline and every 12 months. Laboratory measures of lipid and liver metabolism, hemostatic and hormonal parameters were investigated in a subgroup of 15 women. Adverse events including bleeding disturbances and depressive symptoms were recorded. RESULTS:In 22 women, dienogest was begun after laparoscopy; median EAPP score was 70 mm pre-surgery and 10, 10, 20, 20, and 20 mm, respectively, after 12, 24, 36, 48, and 60 months of dienogest treatment. Another 15 women began dienogest without prior surgery; median EAPP score was 80 mm pretreatment and 20, 20, 30, 30, and 30 mm, respectively, after 12, 24, 36, 48, and 60 months. All laboratory parameters remained within the normal range. Mean serum estradiol was 28 ± 12 pg/ml after 60 months. Seven women experienced spotting episodes and four women presented with phases of depressed mood, which could all be clinically managed. CONCLUSIONS:Long-term (60-month) treatment with dienogest 2 mg once-daily in women with endometriosis effectively reduced EAPP and avoided pain recurrence post-surgery. Dienogest was well tolerated and adverse effects were clinically managed. 10.1007/s00404-018-4864-8
    Dienogest for Treatment of Endometriosis in Women: A 28-Week, Open-Label, Extension Study. Yu Qi,Zhang Shulan,Li Huajun,Wang Ping,Zvolanek Michal,Ren Xiaowei,Dong Liying,Lang Jinghe Journal of women's health (2002) BACKGROUND:Dienogest provided significantly greater reduction in endometriosis-associated pelvic pain (EAPP) than placebo in a 24-week, randomized, double-blind study of Chinese women with endometriosis. The current open-label extension study investigated the efficacy and safety of dienogest for 28 additional weeks in this population. PATIENTS AND METHODS:Women with endometriosis were eligible to enroll at completion of the 24-week, placebo-controlled study (n = 220). All women, regardless of prior study treatment, received dienogest 2 mg once daily for up to 28 weeks. Absolute change in EAPP from baseline on a 1-100 mm visual analog scale (VAS), bleeding pattern, adverse events (AEs), laboratory parameters, and bone mineral density (BMD) were evaluated. RESULTS:The open-label study was completed by 203 (92.3%) women. At the end of open-label study, mean (SD) change from baseline in EAPP score on VAS was -43.1 mm (26.54 mm) and -39.8 mm (31.15 mm) in the prior-dienogest and prior-placebo groups, respectively. Other assessments confirmed that dienogest maintained or enhanced efficacy after 28 weeks of additional treatment. Dienogest initiation was associated with longer, but fewer, spotting/bleeding episodes. Bleeding frequency and intensity decreased progressively during continued treatment. Treatment-emergent AEs, generally mild or moderate, led to withdrawal in 2 (0.9%) patients during the open-label study. Dienogest had no effect on BMD. CONCLUSIONS:Dienogest 2 mg once daily is effective and safe in the long-term management of EAPP in Chinese women with endometriosis, with progressive decreases in EAPP and bleeding irregularities during continued treatment. Efficacy and safety results of this study were consistent with previous studies in Caucasian patients. 10.1089/jwh.2018.7084
    Symptom-alleviating effect and adverse effect of dienogest in Korean women with endometriosis. Jeong Seon Hwa,Lee Dayong,Kim Seul Ki,Jee Byung Chul Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology The purpose was to evaluate the effects of dienogest on Korean women with endometriosis. A cross-sectional questionnaire-based survey was conducted for 100 premenopausal women. They had taken or were taking 2 mg of dienogest daily. We assessed the pelvic pain score and quality-of-life (QOL) score before and after taking dienogest as well as the prevalence of short-term (≤12 weeks) and long-term adverse effects (>52 weeks). Patients were classified into three groups: dienogest treatment immediately following surgery (A), dienogest treatment for a recurrence of endometriosis after surgery (B), or dienogest treatment without any surgery (C). In groups A and C, the median pain score (from 5 to 0,  <.001; from 7 to 1.5,  <.001) and median QOL score (from 10 to 5,  = .002; from 7.5 to 6.5,  = .008) were significantly decreased. Irregular bleeding and decreased menstrual flow were more prevalent in patients with dienogest intake of fewer than 12 weeks, while amenorrhea, weight gain, hair loss, and dorsal pain were more prevalent in patients with dienogest treatment of over 52 weeks. Accordingly, proper counseling is necessary when prescribing dienogest. 10.1080/09513590.2018.1469610