Search

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).)

Objective: Dienogest (DNG) 2 mg (Visanne) was launched for endometriosis treatment in Europe in 2010. The Visanne Post-approval Observational Study (VIPOS) was designed to assess the safety of DNG 2 mg/day compared to other hormonal endometriosis treatments, focusing especially on clinically relevant depression and anemia., Study Design: Large, prospective, non-interventional, active surveillance study in six European countries. Participants were recruited via gynecologists or specialized centers routinely prescribing endometriosis medication. Self-administered questionnaires during study entry and follow-up collected information on baseline characteristics, health status and endometriosis treatment. Patient-reported anemia and depression cases were validated by health care professionals. Inferential statistics were based on Cox proportional hazards models and crude and adjusted hazard ratios (HR) between cohorts were calculated (including 95% confidence intervals [CI]). Adjustment for potential confounding was performed by including predefined prognostic factors as covariates in the Cox models., Results: Out of 26,430 participants, 11.4% used DNG, 12.8% used other approved endometriosis medications (OAED) and 75.7% used hormonal treatments not approved but frequently used for endometriosis treatment (NAED). At baseline, DNG users more frequently reported a surgically confirmed endometriosis diagnosis, severe endometriosis-associated pain and a history of depression, compared to the other cohorts. Baseline characteristics showed large inter-country variability. Overall, the number of confirmed anemia and depression events were substantially lower than expected. The adjusted HRs for anemia were 1.1 (95% CI, 0.4-2.6) for DNG vs OAED and 1.3 (95% CI, 0.7-2.4) for DNG vs NAED. The adjusted HRs for new or worsening depression were 1.8 (95% CI, 0.3-9.4) for DNG vs OAED and 1.5 (95% CI, 0.8-2.8) for DNG vs NAED., Conclusion: The main limitations encountered (low number of confirmed events and considerable inter-country variability) made a robust statistical analysis and a solid interpretation of the results challenging. However, no safety signal regarding anemia for DNG users could be detected, whereas a slight increase in depression risk cannot be excluded but might be explained by baseline severity of endometriosis or unknown country-specific confounding variables. VIPOS reflected routine use of hormonal endometriosis medications and provided real-world insights into endometriosis management in Europe., (Copyright © 2020 Elsevier B.V. All rights reserved.)

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.

Objectives: The objective of this analysis was to identify intra-uterine devices (IUD) perforations detected from 12 to 60 months following IUD insertion, and to combine this information with (our previously published) data about perforations detected in the first 12 months to calculate cumulative perforation rates., Methods and Materials: Prospective, non-interventional cohort study with new users of levonorgestrel-releasing intra-uterine systems (LNG-IUS) and copper-IUD. The original cohort included 61,448 women followed for 12 months. Of these, we had sufficient resources to perform an additional follow-up and analysis at 60 months in 39,009 women. Inclusion criteria for this analysis was insertion prior to 31 July 2010. All potential cases were validated via the health care professional or medical records. Crude and adjusted relative risks were calculated using a logistic regression model., Results: We identified 23 additional perforations (19 LNG-IUS and 4 copper-IUD) more than 12 months after insertion. Added to perforations detected at 12 months, the overall perforation rate was 2.1 per 1000 insertions (95% CI: 1.6-2.8) for LNG-IUS users (40 + 19 perforations/27,630 insertions) and 1.6 per 1000 insertions (95% CI: 0.9-2.5) for copper-IUD users (14 + 4 perforations/11,379 insertions). LNG-IUS users had a borderline higher risk of perforation compared with copper-IUD users (ORadj 1.7; 95% CI: 1.0-2.8). Forty-five (58%) of the 77 perforations were associated with suspected risk factors. Breastfeeding (RR 4.9, 95% CI: 3.0-7.8) and time since delivery (RR 3.0, CI: 1.5-5.4) remained significant risk factors in perforations detected after 12 months. No perforations resulted in serious injury to intra-abdominal or pelvic structures., Conclusions: The incidence of uterine perforations in this study was low, although higher than the commonly reported rate. Approximately one third of perforations are detected 12 months after insertion. Clinical sequalae of perforations are generally mild and associated with a very low risk of injury to intra-abdominal and pelvic structures. Implications Uterine perforation is a rare risk associated with intra-uterine device use. Late diagnosed perforations can occur, although women can be reassured that the morbidity associated with detection and removal is low.

Objectives: The objectives were to identify and compare the incidence of uterine perforation and other medically adverse events associated with levonorgestrel-releasing intrauterine systems (LNG-IUSs, releasing 20 mcg LNG daily) and copper intrauterine devices (IUDs) under routine conditions of use in a study population representative of typical users., Methods and Materials: This is a multinational, prospective, non-interventional cohort study with new users of LNG-IUSs and copper IUDs. In addition to a baseline questionnaire, women and their treating health care professional completed a single follow-up questionnaire after 12 months. All patient-reported outcomes were validated by the treating physicians., Results: A total of 61,448 women in six European countries were followed between 2006 and 2013 for more than 68,000 women-years of observation (70% LNG, 30% copper devices). Overall, 81 uterine perforations were reported: 61 for LNG-IUSs [1.4 per 1000 insertions (95% confidence interval {CI}: 1.1-1.8)] and 20 for copper IUDs [1.1 per 1000 insertions (95% CI: 0.7-1.7)], for an adjusted risk ratio (RRadj) of 1.6 (95% CI: 1.0-2.7) when adjusted for age, body mass index, breastfeeding at time of insertion and parity. Breastfeeding at time of insertion was associated with a sixfold increase (RR 6.1, 95% CI: 3.9-9.6), with no differences between LNG and copper IUD users. Sixty-three of the total 81 perforations were associated with previously suspected risk factors (e.g., breastfeeding, time since last delivery ≤36 weeks). No perforations led to serious illness or to injury of intra-abdominal or pelvic structures., Conclusions: Uterine perforation incidence in this study was low, with a benign clinical course thereafter. The LNG-IUSs and copper IUDs did not have clinically important differences in perforation rates., Implications: The European Active Surveillance Study on Intrauterine Devices is the first large-scale, prospective, non-interventional study to compare the perforation risk in LNG-IUS and copper IUD users. It is the first to examine the independent roles that breastfeeding status and postpartum status have on perforation risk. Conducted during routine clinical practice, the findings are generalizable to broader populations., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: The objective was to measure the rate of unintended pregnancies in women using levonorgestrel-releasing intrauterine systems (LNG IUSs, releasing 20 mcg LNG daily) and copper intrauterine devices (IUDs) in a typical population of IUD users and to describe associated complications., Methods: A multinational, prospective, non-interventional cohort study of new users of LNG IUS and copper IUDs was performed. Following a baseline survey, study participants and their physicians completed one follow-up questionnaire after 12 months. A multifaceted four-level follow-up procedure minimized loss to follow-up. Patient-reported outcomes were validated by the treating physicians., Results: A total of 61,448 women with a newly inserted IUD were enrolled in six European countries between 2006 and 2012. The copper IUD cohort contained more than 30 different types. Validated 1-year follow-up information for 58,324 users between 18 and 50 years of age (70% using LNG IUS, 30% using copper IUDs) was collected. A total of 118 contraceptive failures occurred (26 LNG, 92 copper). Both types of IUD were highly effective, with overall Pearl indices of 0.06 [95% confidence interval (CI): 0.04-0.09] and 0.52 (95% CI: 0.42-0.64) for LNG IUS and copper IUDs, respectively. The adjusted hazard ratio for LNG IUS vs. copper IUDs was 0.16 (95% CI: 0.10-0.25). Tenty-one pregnancies (7 LNG IUS, 14 copper IUD) were ectopic, yielding an adjusted hazard ratio for ectopic pregnancy of 0.26 (95% CI: 0.10-0.66)., Conclusions: The contraceptive failure rate was low with both IUDs. However, the LNG IUS was associated with a significantly lower risk of pregnancy, including ectopic pregnancy, than the copper IUDs., Implications: To our knowledge, this is the first large-scale, multinational, prospective epidemiological study to measure and compare the contraceptive effectiveness of LNG IUSs and copper IUDs during routine clinical practice. Clinicians and patients should be aware of differences in rates of unintended pregnancies and associated complications in relation to IUD us., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: An ad hoc peer-review committee was jointly appointed by Drug Authorities and Industry in Germany, Austria and Switzerland in 1999/2000 to review the evidence for a causal relation between phenacetin-free analgesics and nephropathy. The committee found the evidence as inconclusive and requested a new case-control study of adequate design., Methods: We performed a population-based case-control study with incident cases of end-stage renal disease (ESRD) under the age of 50 years and four age and sex-matched neighborhood controls in 170 dialysis centers (153 in Germany, and 17 in Austria) from January 1, 2001 to December 31, 2004. Data on lifetime medical history, risk factors, treatment, job exposure and intake of analgesics were obtained in a standardized face-to-face interview using memory aids to enhance accuracy. Study design, study performance, analysis plan, and study report were approved by an independent international advisory committee and by the Drug Authorities involved. Unconditional logistic regression analyses were performed., Results: The analysis included 907 cases and 3,622 controls who had never used phenacetin-containing analgesics in their lifetime. The use of high cumulative lifetime dose (3rd tertile) of analgesics in the period up to five years before dialysis was not associated with later ESRD. Adjusted odds ratios with 95% confidence intervals were 0.8 (0.7 - 1.0) and 1.0 (0.8 - 1.3) for ever- compared with no or low use and high use compared with low use, respectively. The same results were found for all analgesics and for mono-, and combination preparations with and without caffeine. No increased risk was shown in analyses stratifying for dose and duration. Dose-response analyses showed that analgesic use was not associated with an increased risk for ESRD up to 3.5 kg cumulative lifetime dose (98 % of the cases with ESRD). While the large subgroup of users with a lifetime dose up to 0.5 kg (278 cases and 1365 controls) showed a significantly decreased risk, a tiny subgroup of extreme users with over 3.5 kg lifetime use (19 cases and 11 controls) showed a significant risk increase. The detailed evaluation of 22 cases and 19 controls with over 2.5 kg lifetime use recommended by the regulatory advisors showed an impressive excess of other conditions than analgesics triggering the evolution of ESRD in cases compared with controls., Conclusion: We found no clinically meaningful evidence for an increased risk of ESRD associated with use of phenacetin-free analgesics in single or combined formulation. The apparent risk increase shown in a small subgroup with extreme lifetime dose of analgesics is most likely an indirect, non-causal association. This hypothesis, however, cannot be confirmed or refuted within our case-control study. Overall, our results lend support to the mounting evidence that phenacetin-free analgesics do not induce ESRD and that the notion of "analgesic nephropathy" needs to be re-evaluated.

Introduction: There is no doubt, oral contraceptives are a safe, reversible and commonly used method of contraception. Ever use is about 80 % in developed countries and current use of OCs about 40 %. Almost all information about prevalence of OC use came from cross-sectional studies and did not distinguish between high- and low-dose OCs. This paper deals with the prevalence of OC use as it was observed during lifetime of a large cohort of German women by calendar year and estrogen content., Methods: The prevalence of OC use between 1980 to 1999 was analysed on occasion of an interim analysis of the German cohort study on women's health. This analysis is based on more than 10 000 women with about 390 000 women-years of observation., Results: The proportion of women under the age of 50, that ever used OCs, increased steeply from 1980, i. e. from 62 % (1980) to about 90 % from 1996 onward. The proportion of current users in a given calendar year rose from 44 % (1980) to 49 % (1991-95) and dropped after the "pill crisis 1995". The percentage of current users who used high-estrogen-dose OCs dropped from 32 % (1980) to 5 % (1999). In contrast, the percentage of users of low-dose OCs of the 2nd generation steeply increased as was the percentage of users of the 3rd generation pills, however the latter dropped after 1995., Conclusion: The high acceptance of oral contraceptives despite many "pill crises" underlines the continuously high appreciation of their efficacy on the one hand, but underscores also the high responsibility of physicians and industry concerning surveillance or reduction of discussed side effects.