Klaas Heinemann

The Menopause Rating Scale (MRS) scale: a methodological review.

AbstractBackgroundThis paper compiles data from different sources to get a first comprehensive picture of psychometric and other methodological characteristics of the Menopause Rating Scale (MRS) scale. The scale was designed and standardized as a self-administered scale to (a) to assess symptoms/complaints of aging women under different conditions, (b) to evaluate the severity of symptoms over time, and (c) to measure changes pre- and postmenopause replacement therapy. The scale became widespread used (available in 10 languages).MethodA large multinational survey (9 countries in 4 continents) from 2001/ 2002 is the basis for in depth analyses on reliability and validity of the MRS. Additional small convenience samples were used to get first impressions about test-retest reliability. The data were centrally analyzed. Data from a postmarketing HRT study were used to estimate discriminative validity.ResultsReliability measures (consistency and test-retest stability) were found to be good across countries, although the sample size for test-retest reliability was small. Validity: The internal structure of the MRS across countries was astonishingly similar to conclude that the scale really measures the same phenomenon in symptomatic women. The sub-scores and total score correlations were high (0.7–0.9) but lower among the sub-scales (0.5–0.7). This however suggests that the subscales are not fully independent.Norm values from different populations were presented showing that a direct comparison between Europe and North America is possible, but caution recommended with comparisons of data from Latin America and Indonesia. But this will not affect intra-individual comparisons within clinical trials.The comparison with the Kupperman Index showed sufficiently good correlations, illustrating an adept criterion-oriented validity. The same is true for the comparison with the generic quality-of-life scale SF-36 where also a sufficiently close association has been shown.ConclusionThe currently available methodological evidence points towards a high quality of the MRS scale to measure and to compare HRQoL of aging women in different regions and over time, it suggests a high reliability and high validity as far as the process of construct validation could be completed yet.

Risk of uterine perforation with levonorgestrel-releasing and copper intrauterine devices in the European Active Surveillance Study on Intrauterine Devices

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.

Cardiovascular risk associated with the use of an etonogestrel-containing vaginal ring.

OBJECTIVE: To compare the risks of short-term and long-term use of an etonogestrel-containing and ethinylestradiol-containing vaginal ring and combined oral contraceptive pills (OCPs) in a routine clinical study population. METHODS: This was a prospective, controlled, noninterventional cohort study performed in the United States and five European countries with the following two cohorts: new users of the vaginal ring and new users of combined OCPs (starters, switchers, or restarters). The study population included 33,295 users of the vaginal ring or combined OCPs recruited by 1,661 study centers. Follow-up of study participants occurred for 2 to 4 years. Main clinical outcomes of interest were cardiovascular outcomes, particularly venous and arterial thromboembolism. These outcomes were validated by attending physicians and further adjudicated by an independent board. Comprehensive follow-up ensured low loss to follow-up. Statistical analyses were based on Cox regression models. Primary statistical variable was the venous thromboembolic hazard ratio (HR) for the vaginal ring compared with combined OCPs. RESULTS: Study participants were followed-up for 66,489 woman-years. Loss to follow-up was 2.9%. The venous thromboembolism incidence rates for the vaginal ring users and combined OCPs users were 8.3 and 9.2 per 10,000 woman-years, respectively. Cox regression analysis yielded crude and adjusted HRs for the vaginal ring users compared with combined OCPs users of 0.9 and 0.8 for venous thromboembolism (95% confidence intervals [CIs] 0.5–1.6 and 0.5–1.5) and 0.8 and 0.7 (95% CIs 0.2–2.5 and 0.2–2.3) for arterial thromboembolism, respectively. CONCLUSION: Vaginal ring use and combined OCP use were associated with a similar venous and arterial thromboembolic risk during routine clinical use. LEVEL OF EVIDENCE: II

Comparative contraceptive effectiveness of levonorgestrel-releasing and copper intrauterine devices: the European Active Surveillance Study for Intrauterine Devices.

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.

Premenstrual symptoms – severity, duration and typology: an international cross-sectional study

Objectives Determine womens experiences of premenstrual symptoms. Study design Cross-sectional survey. Sample In all, 4085 women aged 14–49 years recruited by random telephone digit dialing in France, Germany, Hungary, Italy, Spain, UK, Brazil and Mexico. Main outcome measures Telephone interview checklist of 23 premenstrual symptoms, sociodemographic variables and lifestyle variables. Results The most prevalent symptoms were abdominal bloating, cramps or abdominal pain, breast tenderness, irritability and mood swings. Severity of symptoms is directly proportional to duration (R = 0.79). Hierarchical clustering found the following mental and physical domains and a typology: ‘Mild’ type (40.8%) with minimal symptoms; ‘Moderate M’ type (28.7%) with moderately severe, mostly mental symptoms; ‘Moderate P’ type (21.9%) with moderately severe, mostly physical symptoms; and ‘Severe’ type (8.6%) with severe intensity of both mental and physical symptoms. Multiple stepwise regression found significant effects on symptom duration severity index of age (linear and quadratic effects), current smoking and country. Conclusions Further research is needed on the impact of premenstrual symptoms on quality of life, and whether a brief symptom list could be developed as a valid and reliable tool globally.

Epidemiology of premenstrual symptoms and disorders.

The aim of this paper is to review published literature on the types and prevalences of premenstrual disorders and symptoms, and effects of these on activities of daily life and other parameters of burden of illness. The method involved review of the pertinent published literature. Premenstrual disorders vary in prevalence according to the definition or categorization. The most severe disorder being premenstrual dysphoric disorder (PMDD) affects 3–8% of women of reproductive age. This disorder focuses on psychological symptoms whereas global studies show that the most prevalent premenstrual symptoms are physical. Both psychological and physical symptoms affect womens activities of daily life. A considerable burden of illness has been shown to be associated with moderate to severe premenstrual disorders. In conclusion, premenstrual symptoms are a frequent source of concern to women during their reproductive lives and moderate to severe symptoms impact on their quality of lives.

Benign gynecological tumors: estimated incidence. Results of the German Cohort Study on Women's Health.

OBJECTIVE To analyze the lifetime incidence of benign gynecological tumors. STUDY DESIGN The German Cohort Study on Womens Health was launched in 1998 as historic cohort study with prospective follow up. The study ascertained self-reported information on tumors by calendar time. The incidence of benign gynecological tumors was calculated from the data of the first cohort period. RESULTS The cohort comprised 396000 women-years of observation and 1676 benign tumors were observed. This lead to incidence estimates of 27.0, 18.6, and 23.3 per 100000 women-years of observation for all benign tumors of the uterus, ovary, and breast respectively. CONCLUSION In absence of other data, it is reasonable to use incidence rates generated by a large cohort of German women as a best estimate for the population up to 65 years of age.

The effect of premenstrual symptoms on activities of daily life

OBJECTIVE To assess impact of premenstrual symptoms on activities of womens daily lives (ADL). DESIGN Cross-sectional population-based survey. SETTING Market research company. PATIENT(S) A total of 4,085 women aged 14-50 years recruited by random telephone digit dialing in France, Germany, Hungary, Italy, Spain, the United Kingdom, Brazil, and Mexico. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) A telephone interview checklist of 23 premenstrual symptoms, sociodemographic and lifestyle variables, and ADL effects (global question and seven areas). Stepwise regression measured the effect of premenstrual symptoms and sociodemographic factors on ADL. RESULT(S) Symptoms and symptom domains (physical and mental) had similar negative effects on ADL. Activities of daily life were predominantly affected by symptom severity. Income level, age, and country also significantly affected ADL. In all, 2,638 women (64.6%) were minimally affected in ADL, 981 (24%) were moderately affected, and 454 (11.1%) were severely affected. CONCLUSION(S) Both physical and mental premenstrual symptoms have significant impact on quality of life, assessed as ADL. Up to 35% of women of reproductive age in Europe and Latin America were moderately or severely affected in ADL by cyclical premenstrual symptoms.

Intercountry Assessment of the Impact of Severe Premenstrual Disorders on Work and Daily Activities

We explored the effects of premenstrual symptoms in women suffering from moderate-to-severe premenstrual syndrome/premenstrual dysphoric disorder (PMS/PMDD) on work productivity, absenteeism, and daily life activities in a large, worldwide exploratory study. Women aged 15–45 years from 19 countries in North America, Latin America, Europe, Asia, and Australia were screened for suspected PMS and PMDD and invited to participate in this 2-month web-based survey. Overall, 4,032 women completed all administered questionnaires and represent the analysis set. Women suffering from moderate-to-severe PMS/PMDD had increased work absenteeism and work productivity impairment due to premenstrual symptoms relative to those with mild PMS/no perceived symptoms.

Global study of women's experiences of premenstrual symptoms and their effects on daily life

Objectives. To determine cross-cultural and other effects on womens experiences of premenstrual symptoms and their impact on activities of daily life (ADL). Study design. Cross-sectional survey. Sample. A total of 7226 women aged 15–49 recruited by random sampling with approximately 400 each from France, Germany, Hungary, Italy, Spain, UK, Brazil, Mexico, Hong Kong, Pakistan and Thailand. Approximately 1000 women in Japan and Korea and 500 Australian women were found using Internet panels. Main outcome measures. Questionnaire of 23 premenstrual symptoms, sociodemographic and lifestyle variables, ADL and womens knowledge of premenstrual terms. Results. The most prevalent symptoms were abdominal bloating, cramps or abdominal pain, irritability, mastalgia and joint/muscle/back pains. Severity of symptoms was directly proportional to duration (number of affected cycles) (R — 0.78). A linear model found that symptom prevalence (duration × severity) was associated with age (linear and quadratic effects), parity, current smoking and country. Premenstrual physical and mental symptom domains had similar negative effects on ADL. Impact on ADL was affected by education and exercise participation. Womens knowledge of the terms premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD) varied by symptom intensity, age, education and country. Conclusions. Four of the five most prevalent premenstrual symptoms were physical. There was a great deal of similarities of womens experiences of these symptoms across countries and regions. Womens knowledge of PMS terms is highly dependent on the country in which they live.