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Thomas Strowitzki,1 Thomas Faustmann,2 Christoph Gerlinger,3,4 Ulrike Schumacher,5,6 Christiane Ahlers,7 Christian Seitz8 1Department of Gynecological Endocrinology and Reproductive Medicine, University of Heidelberg, Heidelberg, Germany; 2Bayer Pharma AG, Global Medical Affairs Women’s Healthcare, Berlin, Germany; 3Bayer Pharma AG, Global Research and Development Statistics, Berlin, Germany; 4Department of Gynecology, Obstetrics, and Reproductive Medicine, University Medical School of Saarland, Homburg/Saar, Germany; 5Jenapharm GmbH & Co KG, Medical Affairs Support, Jena, Germany; 6Center for Clinical Studies, Universitätsklinikum Jena, Jena, Germany; 7Bayer Pharma AG, Global Integrated Analysis and Lifecycle Management Statistics, Wuppertal, Germany; 8Bayer Pharma AG, Global Clinical Development Therapeutic Area Primary Care and Women’s Healthcare, Berlin, Germany Background: In four randomized, controlled, European trials, dienogest 2 mg once daily demonstrated significant efficacy for lesion reduction and reduction in pain intensity in endometriosis. We describe a pooled analysis of the safety and tolerability data from these trials to confirm and further characterize the safety profile of dienogest in the treatment of endometriosis.Methods: All 332 women treated with dienogest 2 mg who participated in the four clinical trials were included in the pooled analyses for safety assessments, including adverse events, laboratory tests, vital signs, body weight, and bleeding patterns. Safety variables were analyzed using descriptive statistics.Results: Pooled analyses of this large patient population confirmed that dienogest 2 mg is well tolerated, with a favorable safety profile extending over a period up to 65 weeks in women with endometriosis. The most common adverse drug reactions were headache, breast discomfort, depressed mood, and acne, each occurring in

In this study, a spatiotemporal characterization of forced and unforced flows of a conical swirler is performed based on particle image velocimetry (PIV) and laser Doppler anemometry (LDA). The measurements are performed at a Reynolds number of 33,000 and a swirl number of 0.71. Axisymmetric forcing is applied to approximate the effects of thermoacoustic instabilities on the flow field at the burner inlet and outlet. The actuation frequencies are set at the natural flow frequency (Strouhal number [St.sub.f] [approximately equal to] 0.92) and two higher frequencies ([St.sub.f] [approximately equal to] 1.3 and 1.55) that are not harmonically related to the natural frequency. Phase-averaged measurement are used as a first step to visualize the coherent flow structures. Second, proper orthogonal decomposition (POD) is applied to the PIV data to characterize the effect of the actuation on the fluctuating flow. Measurements indicate a typical natural flow instability of helical nature in the unforced case. The associated induced pressure and flow oscillations travel upstream to the swirler inlet where generally fuel is injected. This observation is of critical importance with respect to the stability of the combustion. Harmonic actuation at different frequencies and amplitudes does not affect the mean velocity profile at the outlet, while the coherent velocity fluctuations are strongly influenced at both the inlet and outlet. On one hand, the dominant helical mode is replaced by an axisymmetric vortex ring if the flow is forced at the natural flow frequency. On the other hand, the natural flow frequency prevails at the outlet under forcing at higher frequencies and POD analysis indicates that the helical structure is still present. The presented results give new insight into the flow dynamics of a swirling flow burner under strong forcing. [DOI: 10.1115/1.2982139] Keywords: swirling flows, PIV, LDA, POD, coherent structures, flow instability, flow forcing

Objective: To evaluate the efficacy and safety of 2 doses of vilaprisan vs. placebo in participants with symptomatic endometriosis., Design: Multicenter, randomized, double-blind, placebo-controlled, parallel-group phase 2b trial (NCT03573336). The initially planned sample size was 315 patients. Recruitment was paused to assess long-term toxicity findings in rodents; although the findings were assessed as likely to be of limited clinical relevance in humans, the study was closed by the sponsor. During the pause, enrolled patients completed 3 or 6 months of treatment per their assigned regimen., Setting: University hospitals, a regional hospital, and a private clinic., Patients: Premenopausal adults with confirmed endometriosis and moderate-to-severe pelvic pain (≥4/10 on a numerical rating scale) were enrolled. Inclusion required protocol adherence, including ≥24 diary entries, and an average pain score of ≥3.5., Intervention: Participants were randomly assigned 1:1:1 to receive vilaprisan (2 mg), vilaprisan (4 mg), or placebo., Main Outcome Measures: The primary outcome was a change in the 7-day mean "worst pain" (per the endometriosis symptom diary item 1) from baseline to month 3. All analyses were descriptive only., Results: Eight participants were randomly assigned to treatment before the study pause: 6 received vilaprisan (4 mg, n = 4 and 2 mg, n = 2), and 2 received placebo. The 6 vilaprisan recipients experienced an improvement in endometriosis-associated pelvic pain, whereas the 2 placebo recipients experienced no change or increased pain; all 8 participants had decreased use of pain medication. Bleeding intensity decreased from baseline in the vilaprisan group., Conclusion: The study findings suggest that vilaprisan may improve outcomes in patients with endometriosis. Further studies in larger populations would be needed to accurately assess treatment effects., Clinical Trial Registration Number: NCT03573336., Competing Interests: H.S.T. reports having served as an investigator for previous Bayer-sponsored studies and also reports funding from Abbvie and consulting fees from Organon outside the submitted. L.D. reports having served as a full-time employee of Bayer at the time of the study and also reports funding from Bayer for the submitted work and funding and stock options from Bayer outside the submitted work. J.H. reports having served as an investigator for previous Bayer-sponsored studies and also reports funding from Bayer for the submitted work. P.O. reports having served as an investigator for previous Bayer-sponsored studies and also reports to the advisory board for Ryeqo outside of the submitted work. K.T. reports having served as an investigator for previous Bayer-sponsored studies and reports stock options to the Austrian Society of OBGYN outside the submitted work. R.W. reports having served as an investigator for previous Bayer-sponsored studies and also reports consulting fees from Gedeon Richter; honoraria from Gedeon Richter and Intuitive; patents for noninvasive diagnosis of endometriosis; and stock options from Novartis outside the submitted work. T.F. reports having served as a full-time employee of Bayer at the time of the study. E.G.W. reports being a full-time employee of Bayer. X.R. reports being a full-time employee of Bayer. C.S. reports being a full-time employee of Bayer. C.S. also reports funding from Bayer AG Berlin, Germany, for the submitted work; patents on use issued by vilaprisan; and stock options issued by Bayer AG outside the submitted work., (© 2024 The Authors.)

Objective: Vilaprisan is a highly potent selective progesterone receptor modulator shown to reduce heavy menstrual bleeding, induce amenorrhea, and diminish uterine fibroid volume in phase 2 studies. The objective of ASTEROID 3 was to demonstrate the superiority of vilaprisan compared with placebo in the treatment of heavy menstrual bleeding in women with uterine fibroids., Design: Randomized, double-blind, placebo-controlled, multicenter phase 3 study., Setting: Hospitals and medical centers., Patient(s): Women with ≥1 uterine fibroid of ≥3 cm and heavy menstrual bleeding of >80 mL/cycle., Intervention(s): Women were randomly assigned to 1 of 4 treatment arms, which were planned to comprise 2 treatment periods of 12 weeks, each with vilaprisan (2 mg/d) or placebo that were continuous or separated by a break of one bleed., Main Outcome Measure(s): Amenorrhea (primary end point; <2 mL in the last 28 days of treatment) and heavy menstrual bleeding response (key secondary end point; <80 mL/cycle and >50% reduction in bleeding from baseline) were measured with the alkaline hematin method. Change in volume of the 3 largest fibroids from baseline to end of treatment was assessed by ultrasound. Safety was monitored throughout the study., Result(s): Overall, 75 women completed the first 12 weeks of treatment. Statistically significant and clinically meaningful differences were observed between the vilaprisan- and placebo-treated groups in both the full analysis and per-protocol sets. In the per-protocol set (n = 36 and n = 12 for the vilaprisan and placebo groups, respectively), amenorrhea was observed more frequently in women treated with vilaprisan than in those who received placebo (83.3% vs. 0%, P<.0001), with a median time to onset of 3 days in the vilaprisan group. Similarly, more vilaprisan- than placebo-treated women achieved a response in heavy menstrual bleeding (91.7% vs. 25.0%, P<.0001). Serious adverse events were reported for 22 (27.8%) of 79 women and were evenly distributed among the 4 groups receiving vilaprisan and/or placebo. None of these events led to study discontinuation or were related to the liver, and no new safety findings were identified compared with the earlier phase 2 ASTEROID studies., Conclusion(s): Vilaprisan is efficacious and well tolerated over 12 weeks in the treatment of heavy menstrual bleeding associated with uterine fibroids. Further investigations of the long-term efficacy and safety of vilaprisan are warranted., Clinical Trial Registration Number: NCT03400943 (ClinicalTrials.gov)., Competing Interests: Declaration of interest A.A-H. reports funding from National Institutes of Health; consulting fees from AbbVie, Bayer, ObsEva, and Myovant Sciences; and a patent for novel diagnostics and therapeutics for uterine sarcoma (US Patent No. 9,790,562 B2) outside the submitted work. Y.F.Z. has nothing to report. E.G-W., S.P., and C.S. are employees of Bayer AG; T.F. is a former employee of Bayer AG. K.L. is an employee of Bayer Nordic SE., (Copyright © 2023 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Endometriosis is a chronic disease that requires a suitable, lifelong treatment. To our knowledge, the Visanne Post-approval Observational Study (VIPOS) is to date the largest real-world, non-interventional study investigating hormonal management of endometriosis. We describe women's experiences of endometriosis in the real world by considering their symptoms and the diagnostic process in their healthcare setting. Overall, 27,840 women were enrolled from six European countries via networks of gynecologists or specialized centers. Of these, 87.8% of women were diagnosed based on clinical symptoms; the greatest and lowest proportions of women were in Russia (94.1%) and Germany (61.9%), respectively. Most women (82.8%) experienced at least one of the triad of endometriosis-associated pain symptoms: pelvic pain, pain after/during sexual intercourse, and painful menstrual periods. The most frequently reported endometriosis-associated symptoms were painful periods (61.8%), heavy/irregular bleeding (50.8%), and pelvic pain (37.2%). Women reported that endometriosis impacted their mood; 55.6% reported feeling "down", depressed, or hopeless, and 53.2% reported feeling like a failure or having let down family/friends. VIPOS broadens our understanding of endometriosis based on real-world data by exploring the heterogeneity of symptoms women with endometriosis experience and the differences in diagnostic approaches between European countries.Trial registration: ClinicalTrials.gov, NCT01266421; registered 24 December 2010. Registered in the European Union electronic Register of Post-Authorisation Studies as number 1613., (© 2021. The Author(s).)

Since its introduction in 1990, the levonorgestrel-releasing intrauterine system (LNG-IUS) has played a key role in shaping the healthcare landscape of women. Here we explore the development of the first LNG-IUS (Mirena®) and the early clinical trials that demonstrated its potential. We highlight the contraceptive and therapeutic benefits of Mirena®, and discuss how clinical practice has been changed since the introduction of LNG-IUS and other long-acting reversible contraceptive methods. The history of Mirena® is rich in innovation and has also paved the way to the development of smaller intrauterine systems with lower hormone doses. Along with Mirena®, these newer LNG-IUS contribute to improving contraceptive choices for women, allowing them to select the option that is right for them and that meets their needs no matter their age, parity or circumstances., (© 2021 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Objective: To assess the efficacy of vilaprisan compared with placebo in the management of the symptoms of uterine fibroids (UF), with a secondary objective to provide a descriptive comparison with ulipristal acetate., Study Design: The randomized, parallel-group, double-blind, placebo- and active-controlled, multicenter ASTEROID 2 trial assessed the efficacy and safety of vilaprisan versus placebo and ulipristal acetate for two 12-week treatment periods in women with ≥1 UF experiencing heavy menstrual bleeding (HMB). The primary endpoint compared the efficacy of vilaprisan with placebo at 12 weeks, assessed as the absence of bleeding/spotting by bleeding diary. Secondary endpoints compared the efficacy of vilaprisan with ulipristal acetate. Results of the first 12-week treatment period are reported here., Results: Women (mean age 42.5 years) were enrolled from 1 June 2015. At baseline, mean menstrual blood loss per 28 days was 214.1 mL and the volume of the three largest UF was 106.2 mL. In total, 155 women completed the initial 12-week treatment period. Complete absence of bleeding/spotting until the end of the 12-week treatment period was achieved by 62.9 % of women receiving vilaprisan versus 0.0 % with placebo (p < .001); 55.4 % of women treated with ulipristal acetate reported absence of bleeding/spotting. The predefined HMB response (<80 mL and >50 % reduction from baseline during the last 28 days of treatment) was observed in 95.7 % of subjects treated with vilaprisan and 86.5 % of subjects treated with ulipristal acetate. Vilaprisan and ulipristal acetate treatment reduced the sum of the volume of the three largest UF by 29.9 % and 23.8 %, respectively, whereas an increase of 6.3 % was observed in the placebo group. No safety concerns, including multiple laboratory parameters, were identified., Conclusion: Daily administration of vilaprisan 2 mg induced amenorrhea, controlled bleeding, decreased UF size, and was well tolerated in women with HMB associated with UF., Clinical Trial Registration: ClinicalTrials.gov number: NCT02465814 https://clinicaltrials.gov/ct2/show/NCT02465814., (Copyright © 2020. Published by Elsevier B.V.)

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.

Purpose: Evidence from real-world settings is important to provide an accurate picture of health care delivery. We investigated use of long-acting reversible contraception (LARC) in women aged 15-49 years. Materials and methods: Two surveys, one of women and one of health care professionals (HCPs), were conducted in parallel across seven countries. Participating women completed an online survey to assess contraceptive awareness, current method of contraception, age, and experience with current contraceptive method. HCPs participated in an online survey to provide practice-level information and three anonymous charts of hormonal LARC users. Results: Of 6903 women who completed the survey, 3225 provided information about their current primary contraception method. Overall, 16% used LARC methods, while 52% used oral contraceptives (OCs). Of hormonal intrauterine system users, 72% described their experience as 'very favourable', compared with only 53% of women using OCs. Anonymous patient records ( n  = 1605) were provided by 550 HCPs who completed the online survey. Most women (64%) had used short-acting reversible contraception before switching to LARC. Physicians perceived 56-84% of LARC users to be highly satisfied with their current form of contraception. Conclusions: Although usage of LARC was low, most women using LARC were highly satisfied with their method of contraception.

Objective: To evaluate the efficacy and safety of a new, low-dose levonorgestrel intrauterine contraceptive system (LNG-IUS 12) for up to 5 years of use., Study Design: In this Phase III study, 2885 nulliparous and parous women aged 18-35 years were randomized to LNG-IUS 8 or LNG-IUS 12 for 3 years. After 3 years, women using LNG-IUS 12 could continue for up to 2 additional years (5 years total). The primary outcome was occurrence of pregnancy (Pearl Index). Secondary outcomes included safety, bleeding, dysmenorrhea, discontinuations, and user satisfaction., Results: From August 2007 through May 2008, out of 2885 women who were enrolled, 1453 were randomized to LNG-IUS 12. Placement was attempted in 1452/1453 (full analysis set). Mean age at baseline was 27.1 years; 39.5% were nulliparous. The cumulative 5-year Pearl Index (PI) was 0.29; the 5-year cumulative failure rate was 1.4%. The 5-year PI for ectopic pregnancy was 0.18. Over 5 years, 55.3% of women reported study drug-related treatment-emergent adverse events (TEAEs). Crude incidences of pelvic inflammatory disease, uterine perforation, and complete/partial LNG-IUS 12 expulsion were 0.6%, 0.2%, and 3.7%, respectively. Women using LNG-IUS 12 generally experienced less frequent bleeding over time. The incidence of amenorrhea during the last 90-day reference interval (end of Year 5) was 22.6%. Overall, 870 (59.9%) and 550 (37.9%) women completed 3 and 5 years of treatment, respectively; 77.8% of women who entered the extension phase completed 5 years of use. Over 5 years, 22.6% discontinued due to TEAEs, including 13 women who discontinued due to pregnancy; 76 discontinued due to bleeding problems including amenorrhea; and 163 discontinued due to desire for pregnancy, 71.2% of whom conceived within 12 months., Conclusion: In this study including parous and nulliparous women, LNG-IUS 12 was highly effective over 5 years of use and associated with a favorable safety profile. LNG-IUS 12 offers women a low-dose contraceptive option for up to 5 years., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Dienogest offers pharmacological advantages for the effective treatment of endometriosis and for use in contraception and hormone replacement therapy. This pharmacodynamic study investigated the ovulation-inhibiting effects of dienogest monotherapy in healthy women. Dienogest was administered at 0.5, 1, 2, or 3 mg daily for up to 72 days to women aged 18 to 35 years (n = 102). Ovarian activity was assessed pretreatment and during 2 treatment periods (days 0-36 and days 37-72) by the Hoogland score, based on follicle size and serum estradiol and progesterone levels. Additional hormonal parameters and endometrial thickness were assessed. Hoogland scoring indicated ovulation in all women pretreatment, decreasing to 3 of 21, 1 of 23, 0 of 20, and 0 of 23 women in the 0.5-, 1-, 2-, and 3-mg groups, respectively (per-protocol set). Maximum serum estradiol concentrations were similar to pretreatment levels in the 0.5- or 1-mg group and decreased moderately (within physiologic levels) in the 2- or 3-mg group. Endometrial thickness was reduced by all dienogest doses. Hormonal changes during follow-up indicated resumption of ovulation in most women, shortly after treatment cessation. Dienogest ≥2 mg daily provides moderate suppression of estradiol production and reliable ovulation inhibition, which reverses rapidly after treatment cessation.

Objective: To analyze the secondary efficacy and safety outcomes from a recent trial comparing dienogest (DNG) with leuprolide acetate (LA) in women with endometriosis., Methods: A 24-week, open-label, randomized, multicenter study of DNG versus LA in women with endometriosis-related pain was assessed for outcomes such as responder rates (using predefined thresholds of pain relief), changes in single symptoms/signs and sum scores from the Biberoglu and Behrman (B&B) scale, clinical laboratory parameters, and measures of quality of life., Results: Dienogest was non-inferior to LA for treatment response using all predefined thresholds of pain relief and provided equivalent improvements in B&B symptoms and signs. No clinically relevant changes in laboratory parameters were observed during DNG treatment, whereas estrogen levels decreased in the LA group. Compared with LA, DNG was associated with pronounced improvements in specific quality-of-life measures., Conclusion: The analyses provide supportive evidence that the efficacy of DNG is equivalent to that of LA for treating endometriosis symptoms, with specific quality-of-life benefits and a favorable safety profile., (Copyright © 2012 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.)

Approaches to the treatment of endometriosis vary worldwide, but studies comparing endometriosis medications in different ethnic groups are rare. A systematic literature search identified two studies directly comparing dienogest (DNG) versus gonadotropin-releasing hormone (GnRH) analogues in European and Japanese populations. Meta-analysis of visual analogue scale scores revealed no heterogeneity in response between the trials, indicating equivalent efficacy of DNG and GnRH analogues for endometriosis-related pain across populations. DNG was significantly superior to GnRH analogues for bone mineral density change in both trials, but significant heterogeneity between the studies may indicate ethnic differences in physiology.

Purpose: To investigate the efficacy and safety of dienogest as a long-term treatment in endometriosis, with follow-up after treatment discontinuation. The study included women with endometriosis, who had previously completed a 12-week, placebo-controlled study of dienogest, who participated in an open-label extension study for up to 53 weeks. Thereafter, a patient subgroup was evaluated in a 24-week follow-up after treatment discontinuation., Methods: A multicenter study performed in Germany, Italy and Ukraine. Women with endometriosis were enrolled at completion of the placebo-controlled study (n = 168). All women received dienogest (2 mg once daily, orally) and changes in pelvic pain (on a visual analog scale), bleeding pattern, adverse events and laboratory parameters were evaluated during and after treatment., Results: The completion rate among women who entered the open-label extension study was 90.5% (n = 152). A significant decrease in pelvic pain was shown during continued dienogest treatment (P < 0.001). The mean frequency and intensity of bleeding progressively decreased. Adverse events, rated generally mild or moderate, led to withdrawal in four patients (2.4%). No clinically relevant changes in laboratory parameters were observed. During treatment-free follow-up (n = 34), the reduction in pelvic pain persisted, while bleeding frequency and intensity returned to normal patterns., Conclusions: Long-term dienogest showed a favorable efficacy and safety profile, with progressive decreases in pain and bleeding irregularities during continued treatment; the decrease of pelvic pain persisted for at least 24 weeks after treatment cessation.

Background: When comparing active treatments, a non-inferiority (or one-sided equivalence) study design is often used. This design requires the definition of a non-inferiority margin, the threshold value of clinical relevance. In recent studies, a non-inferiority margin of 15 mm has been used for the change in endometriosis-associated pelvic pain (EAPP) on a visual analog scale (VAS). However, this value was derived from other chronic painful conditions and its validation in EAPP was lacking., Methods: Data were analyzed from two placebo-controlled studies of active treatments in endometriosis, including 281 patients with laparoscopically-confirmed endometriosis and moderate-to-severe EAPP. Patients recorded EAPP on a VAS at baseline and the end of treatment. Patients also assessed their satisfaction with treatment on a modified Clinical Global Impression scale. Changes in VAS score were compared with patients' self-assessments to derive an empirically validated non-inferiority margin. This anchor-based value was compared to a non-inferiority margin derived using the conventional half standard deviation rule for minimal clinically important difference (MCID) in patient-reported outcomes., Results: Anchor-based and distribution-based MCIDs were-7.8 mm and-8.6 mm, respectively., Conclusions: An empirically validated non-inferiority margin of 10 mm for EAPP measured on a VAS is appropriate to compare treatments in endometriosis.

Objective: To investigate the efficacy and safety of oral dienogest 2mg compared with placebo in the treatment of endometriosis-associated pelvic pain (EAPP)., Study Design: This was a 12-week, randomized, double-blind, placebo-controlled, multicenter (n=33) study in Germany, Italy, and Ukraine of 198 women aged 18-45 years with laparoscopically confirmed endometriosis and EAPP score > or =30 mm on a visual analog scale (VAS). Dienogest 2mg or placebo was administered orally once daily. The primary efficacy variable was absolute change in EAPP from baseline to Week 12, as determined by the target variables of change in VAS score and change in intake of supportive analgesic medication (ibuprofen) for pelvic pain., Results: Mean reductions in VAS score between baseline and Week 12 in the full analysis set were 27.4 mm and 15.1mm in the dienogest and placebo groups, respectively-a significant score difference of 12.3 mm in favor of dienogest (P<0.0001). Changes in intake of supportive analgesic medication were modest in both groups. The primary efficacy measure of absolute change in EAPP demonstrated the superiority of dienogest over placebo. Dienogest was generally well tolerated and few adverse events were associated with therapy., Conclusions: Dienogest at a dose of 2mg daily for 12 weeks was significantly more effective than placebo for reducing EAPP., (Copyright 2010 Elsevier Ireland Ltd. All rights reserved.)

Hormone replacement therapy (HRT) remains the most effective treatment for menopausal symptom relief, and may provide cardiovascular benefits in younger women initiating treatment soon after menopause. However, large surveys indicate that many symptomatic women refuse or discontinue HRT prematurely owing to fear of weight gain. A continuous combined HRT containing 17beta-estradiol (E(2)) 1 mg plus drospirenone (DRSP) 2 mg is effective in relieving menopausal symptoms and preventing postmenopausal osteoporosis. DRSP is a unique synthetic progestogen with a pharmacological profile similar to that of natural progesterone, including antialdosterone activity, a property not exhibited by other synthetic progestogens. DRSP can therefore reduce estrogen-related sodium and water retention in postmenopausal women receiving HRT via the renin-angiotensin-aldosterone system, which regulates sodium and water balance. This may translate into weight benefits. Pooled data from two placebo-controlled clinical trials (n = 333) indicated statistically significant weight loss of -1.5 kg at 6 and 12 months in postmenopausal women receiving E(2)/DRSP vs. placebo (p < 0.001). In a third randomized controlled trial (n = 1147), women receiving E(2)/DRSP maintained or lost weight, whereas weight increases were observed in women receiving E(2) monotherapy (p < 0.0125). E(2)/DRSP could help maintain or even slightly decrease body weight during treatment, potentially improving HRT acceptance and compliance.