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.

Tradução e adaptação transcultural para o português brasileiro da Scale for Quality of Sexual Function (QSF) / Translation and cross-cultural adaptation into Brazilian Portuguese of the Scale for Quality of Sexual Function (QSF)

INTRODUÇÃO: Apesar do papel fundamental da função sexual na qualidade de vida da população, há uma escassez na literatura brasileira de instrumentos específicos para sua avaliação e que possam ser utilizados tanto para homens quanto para mulheres. A adaptação da Scale for Quality of Sexual Function (QSF), uma escala unissex, é um passo importante na obtenção de instrumentos que permitam a comparação de resultados entre diferentes populações. OBJETIVO: Descrever o processo de tradução e adaptação semântica da QSF para o português brasileiro. MÉTODOS: A adaptação do instrumento envolveu cinco fases: 1) duas traduções independentes, 2) uma versão de consenso realizada por tradutores e especialistas, 3) avaliação da versão gerada por mais um especialista que não participou das etapas anteriores, 4) retrotradução com avaliação do autor da escala original e, por fim, 5) aplicação da versão obtida em um grupo experimental. RESULTADOS: São descritas todas as etapas de adaptação do instrumento. A participação de especialistas tanto da área de saúde mental quanto de sexualidade humana, desde a primeira fase do processo, contribuiu para discussões amplas, que permitiram a melhor adequação dos itens, tanto conceitual quanto culturalmente. Participaram da aplicação experimental sujeitos de diferentes níveis de escolaridade de ambos os sexos, não sendo detectadas dificuldades na compreensão dos itens. CONCLUSÃO: Por meio dos procedimentos adotados, foi possível elaborar uma versão da QSF em português brasileiro.

INTRODUCTION: Despite the important role played by sexual function in quality of life, there is a scarcity of instruments in the Brazilian literature specifically designed to assess this aspect, and especially of instruments that can be used with both men and women. The adaptation of the Scale for Quality of Sexual Function (QSF), a unisex scale, is an important step in the production of instruments that allow to compare results obtained in different populations. OBJECTIVE: To describe the translation and semantic adaptation of the QSF into Brazilian Portuguese. METHODS: Instrument adaptation involved five phases: 1) two independent translations, 2) a consensual version produced by translators and experts, 3) evaluation of this version by a different expert, not involved in the previous phases, 4) back translation with evaluation by the author of the original scale, and, finally, 5) application of the final Brazilian Portuguese version in a experimental group. RESULTS: All stages of the adaptation process are described. The participation of experts from the fields of both mental health and human sexuality since the first stage of the process contributed to broader discussions, which allowed to achieve the best possible adequacy for each item, both conceptually and culturally. The experimental application of the final, adapted version of the scale involved both men and women with different educational backgrounds and levels. No difficulties were faced by this group in understanding the items included in the scale. CONCLUSION: The procedures and process herein described successfully allowed to develop a Brazilian Portuguese version of the QSF.

Use of oral contraceptives containing gestodene and risk of venous thromboembolism: outlook 10 years after the third-generation "pill scare".

BACKGROUND: This study investigated whether gestodene-containing oral contraceptives (OCs) carry a higher risk of venous thromboembolism (VTE) than OCs containing progestins other than desogestrel and gestodene. The study was conducted based on the hypothesis that the biases and confounding factors that were present initially after the introduction of new so-called "third-generation" OCs (i.e., those containing desogestrel and gestodene) in the 1990s, which likely contributed to the alleged increased risk of VTE, may have vanished after 10 years. STUDY DESIGN: This was a matched case-control study using data identified for women (aged 15-49 years) with suspected or diagnosed VTE (deep vein thrombosis or pulmonary embolism) that occurred between January 2002 and February 2006 in Austria. All VTE cases were validated by an attending/relevant physician(s), a detailed review of medical records and patient-completed questionnaires. Data were analyzed using an unconditional logistic regression model with adjustment for relevant confounders. RESULTS: Overall, 451 VTE cases and 1,920 controls without VTE were identified. The adjusted odds ratios for confirmed VTE with OC use versus nonuse were: 3.39 (95% CI 2.36-4.87) for OCs containing gestodene and 3.14 (2.1-4.47) for OCs containing progestins other than desogestrel and gestodene. Adjusted odds ratios for a head-to-head comparison of OCs containing gestodene versus OCs containing progestins other than desogestrel and gestodene were: 0.99 (0.68-1.45) for all cases; 1.01 (0.69-1.47) for confirmed cases and 1.11 (0.73-1.69) for confirmed and idiopathic VTE cases, respectively. CONCLUSION: The risk of VTE is not elevated in users of gestodene-containing OCs relative to users of OCs containing progestins other than desogestrel and gestodene. Our study supports the view that (i) the majority of previous results may be explained by differences in the user populations of so-called "third-generation" OCs (containing desogestrel and gestodene) and "second-generation" OCs (containing progestins other than desogestrel and gestodene) that were present shortly after market introduction of gestodene-containing OCs and that (ii) these differences seem to have disappeared over time.

Explorative evaluation of the impact of severe premenstrual disorders on work absenteeism and productivity.

PURPOSE: To assess the effects of premenstrual disorders on work productivity and absenteeism in the multinational Impact study. METHODS: Women aged 15-45 years were screened for suspected premenstrual dysphoric disorders (PMDD) and premenstrual syndrome (PMS) and invited to participate in this web-based study. Based on the Daily Record of Severity of Problems (DRSP) questionnaire, symptoms were assessed prospectively over 2 months. Participants were categorized as having no perceived symptoms/mild PMS or moderate-to-severe PMS/PMDD based on a validated algorithm. Work productivity impairment and absenteeism were assessed retrospectively using the Premenstrual Symptoms Screening Tool (PSST) and a modified version of the Work Productivity and Activity Impairment (WPAI) questionnaire. Work productivity impairment was also assessed prospectively over 2 months using the DRSP questionnaire. RESULTS: Overall 1,477 women started the study-of these, 822 (56%) completed the study as planned and represent the full analysis set. Employed women with moderate-to-severe PMS/PMDD had higher rate of productivity impairment on the modified version of the WPAI questionnaire (values >/=7) relative to those with no perceived symptoms/mild PMS (adjusted odds ratio, 3.12; 95% confidence interval, 1.75-5.57). Similar outcomes were obtained for impairment of working productivity or efficiency using the PSST scale (value 4). The mean number of days on the DRSP with at least moderate reduction in productivity or efficiency in daily routine was higher for women with moderate-to-severe PMS/PMDD (5.6 vs. 1.1). Women with moderate-to-severe PMS/PMDD had a higher rate of absenteeism (>8hours per cycle; 14.2% vs. 6.0%). CONCLUSION: Moderate-to-severe PMS/PMDD seems to be associated with work productivity impairment and increased absenteeism, and thus poses a potential economic burden.

Explorative evaluation of the impact of premenstrual disorder on daily functioning and quality of life.

OBJECTIVES: : To assess the effects of premenstrual disorders on health-related quality of life (HR-QOL), hobbies and social activities, and relationships with others in the multinational IMPACT study. METHODS: : Women aged 15-45 years were screened for suspected premenstrual dysphoric disorder (PMDD) and premenstrual syndrome (PMS) and invited to participate in this web-based study. Based on the Daily Record of Severity of Problems (DRSP), prospectively assessed over two observational cycles, participants were grouped into two categories: no perceived symptoms/mild PMS or moderate-to-severe PMS/PMDD. HR-QOL was assessed retrospectively at baseline using the SF-12. RESULTS: : Overall, 1477 women started the study. Of these, 822 (56%) completed the DRSP and SF-12 questionnaires as planned. Moderate-to-severe PMS/PMDD was associated with a reduction in HR-QOL compared with no perceived symptoms/mild PMS for both mental component scores (34.5 ± 8.7 vs 39.0 ± 9.5) and physical component scores (48.9 ± 7.9 vs 51.1 ± 7.2). Women with moderate-to-severe PMS/PMDD experienced a significantly greater mean number of days with at least moderate interference with hobbies or social activities (5.6 vs 1.1 day; p < 0.05, t-test), and relationships with others (5.4 vs 1.1 day) than those with no perceived symptoms/mild PMS. CONCLUSIONS: : Moderate-to-severe PMS/PMDD has a negative impact on HR-QOL, hobbies and social activities, and relationships with others. Studies with a confirmatory design are needed to confirm these results.

How to measure "short-term hormonal effects"?

Background. Interest to assess short-term benefits or risks of sex-steroid hormone use (OC or HRT) exists for years. However, no validated scale is available to evaluate the broad array of described effects of short-term hormone use. Methods. A raw scale consisting of 43 specific items and 47 general data was developed. Surveys in Italy, Germany and Austria were performed and data analyzed by factorial analyses. The resulting new scale with 15 items underwent reliability and validity investigations. Results. The new scale consists of 15 items in 5 domains. Internal consistency reliability coefficients were satisfactory as were test-retest reliability coefficients. Content and concurrent validity were promising. Conclusion. Psychometric properties of the new scale suggest good characteristics to measure short-term effects of sex-steroid hormones in women. The scale seems to be appropriate, feasible, interpretable, reliable, and valid for their application as PRO scale.

Non-phenacetin analgesics and analgesic nephropathy: clinical assessment of high users from a case-control study.

BACKGROUND: A recent large-scale case-control study on analgesic nephropathy (SAN) [1] found no increased risk of end-stage renal disease (ESRD) in users of combined or single formulations of phenacetin-free analgesics. In a subgroup of 22 high users, however, a dose-dependent increased risk was found, which raised the question if these patients presented or not with analgesic nephropathy (AN). METHODS: The individual questionnaires of this subgroup of high users were reviewed, and the total lifetime intake of different types of analgesics was calculated. For evidence of AN, the following data were considered: (1) the amount and type of analgesics consumed, (2) the cause of ESRD, as diagnosed by the nephrologist in charge of the patient and (3) renal imaging and other relevant laboratory data. RESULTS: This group of ESRD patients consumed on average 7.8 kg of antipyretic analgesics (range 30.8-2.7 kg) over an average of 21.5 years (range 35-6 years). Single analgesics were exclusively used by 12 patients (54.5%) and combined analgesics by 5 patients (22.7%), while 5 patients used both. None of the patients was diagnosed as having AN, and a review of the questionnaires did not disclose evidence suggestive of AN. The possibility that, irrespective of AN, the analgesic (ab)use contributed to the progression of existing renal diseases cannot be answered in the absence of well-defined criteria. The data supporting the existence of such an analgesic-associated nephropathy (AAN) are, however, not consistent and most likely due to confounding by indication. CONCLUSION: In a group of ESRD patients with high use of non-phenacetin analgesics, no evidence of AN was found. There is no evidence that (ab)use of analgesics or NSAIDs other than phenacetin leads to a pathologically or clinically defined renal disease that could be named AN or AAN.

Prevalence and opinions of hormone therapy prior to the Women's Health Initiative: a multinational survey on four continents.

OBJECTIVE: Hormone therapy (HT) is a well-established form of treatment for menopausal symptoms worldwide. Since 2002 when the initial findings of the Women's Health Initiative (WHI) were published, the use of HT has decreased dramatically. This investigation was conducted immediately prior to the initial publication of the WHI and Million Women's Study results and quantifies menopausal women's prevalence of symptoms across nine countries on four continents. In addition, it investigates women's positive and negative motivations for HT use as well as their acceptance of various forms and routes of administration. METHODS: Using national representative population panels and quota samples in nine countries on four continents, 10,297 women aged 40-70 years were recruited between April and June 2002. A validated survey was administered to determine which symptoms women suffered from the most and what their desires were regarding the use and effects of HT. RESULTS: Self-reported symptoms did not differ significantly among menopausal women in Europe, North America, Latin America, and Indonesia. However, the prevalence of HT ever-use ranged from a high of 50% in France to a low of 1.8% in Indonesia (U.S. rate 43%). Oral pills had the highest acceptance rate in all countries. CONCLUSIONS: Women in all parts of the world suffer from symptoms associated with menopause, and many desire treatment. This study was conducted prior to the publication of the initial WHI and Million Women Study results, thereby providing a benchmark of patient attitudes about menopausal symptoms and the acceptability of different types and delivery modes of HT.

Rationale, design and methods of the ESPRIT study: Energy, Sexual desire and body PropoRtions wIth AndroGel, Testosterone 1% gel therapy, in hypogonadal men.

Hypogonadism is associated with a range of disease states that have significant effects on morbidity and mortality, and also affect quality of life. The ESPRIT study (Energy, Sexual desire and body PropoRtions wIth AndroGel, Testosterone 1% gel therapy) is a 6-month, multinational, open label, observational study in hypogonadal men being treated with transdermal AndroGel in usual daily clinical practice; 1,700-2,400 patients will be enrolled in Canada, Germany, Central and Eastern Europe, Russia and the Middle East. The main objective will be to evaluate the effect of AndroGel on symptoms of hypogonadism and quality of life as assessed by the Aging Males' Symptoms scale. Further objectives include evaluating the effect and time to onset of improvement in erectile dysfunction and libido/sexual desire (International Index of Erectile Function), fatigue (Multi-dimensional Fatigue Index) and body composition (waist circumference, body mass index). Subgroup analyses will be performed: <50 years versus > or = 50 years; absence versus presence of metabolic syndrome. The safety of AndroGel will also be assessed. The study population will consist of newly diagnosed hypogonadal men (age > or = 18 years), in whom testosterone deficiency has been confirmed by clinical features and biochemical tests according to international guidelines, who are currently being prescribed AndroGel (testosterone 1% gel, starting dose 50 mg testosterone per day).

Analgesics use and ESRD in younger age: a case-control study.

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.

Colon cancer risk and different HRT formulations: a case-control study.

BACKGROUND: Most studies have found no increased risk of colon cancer associated with hormone replacement therapy (HRT), or even a decreased risk. But information about the effects of different HRT preparations is lacking. METHODS: A case-control study was performed within Germany in collaboration with regional cancer registries and tumor centers. Up to 5 controls were matched to each case of colon cancer. Conditional logistic regression analysis was applied to estimate crude and adjusted odds ratios (OR) and 95% confidence intervals (95% CI). Stratified analyses were performed to get an impression of the risk associated with different estrogens and progestins. RESULTS: A total of 354 cases of colon cancer were compared with 1422 matched controls. The adjusted overall risk estimate for colon cancer (ColC) associated with ever-use of HRT was 0.97 (0.71-1.32). No clinically relevant trends for ColC risk were observed with increasing duration of HRT use, or increasing time since first or last HRT use in aggregate. Whereas the overall risk estimates were stable, the numbers in many of the sub-analyses of HRT preparation groups (estrogens and progestins) were too small for conclusions. Nevertheless, if the ColC risk estimates are taken at face value, most seemed to be reduced compared with never-use of HRT, but did not vary much across HRT formulation subgroups. In particular, no substantial difference in ColC risk was observed between HRT-containing conjugated equine estrogens (CEE) or medroxyprogesterone acetate (MPA) and other formulations more common in Europe. CONCLUSION: Ever-use of HRT was not associated with an increased risk of colon cancer. In contrary, most risk estimates pointed non-significantly toward a lower ColC risk in HRT ever user. They did not vary markedly among different HRT formulations (estrogens, progestins). However, the small numbers and the overlapping nature of the subgroups suggest cautious interpretation.

Range of published estimates of venous thromboembolism incidence in young women.

OBJECTIVE: This review was conducted to show the full range of incidence estimates published for venous thromboembolism (VTE) in women depending on study design and to suggest a more reliable estimate for women of reproductive age. METHODS: A literature search was performed to identify studies on the incidence of VTE in women. Incidence rates were compiled from studies with different methodologies and varying methodological quality. Algorithms were used to estimate VTE incidence from more reliable studies in young women. RESULTS AND DISCUSSION: The literature shows two levels of VTE incidence rates: community/cohort studies and database studies. The estimated VTE incidence for women of reproductive age was 5.5-13.5 and 3.8-12.2 in community and cohort studies, respectively, but only 0.7-3.8 per 10,000 women-years (WY) in database studies. This difference is probably attributable to methodological problems associated with some database studies. CONCLUSION: The VTE incidence in women of reproductive age is likely to be in the range of 5-10 per 10,000 WY. These rates for the background incidence are clearly higher than the reference figures that are often utilized in the comparison with users of hormonal contraception (0.5-1 VTE per 10,000 WY).

The safety of a drospirenone-containing oral contraceptive: final results from the European Active Surveillance Study on oral contraceptives based on 142,475 women-years of observation.

OBJECTIVES: The study was conducted to compare risks of adverse cardiovascular and other events associated with the use of drospirenone (DRSP)-containing oral contraceptives (OCs) and other OCs. METHODS AND MATERIALS: The European Active Surveillance study (EURAS) was a multinational, prospective, noninterventional cohort study of new users of DRSP, levonorgestrel (LNG) and other progestin-containing OCs. Semiannual follow-up was based on mailed questionnaires, with additional follow-up procedures when needed. RESULTS: Overall, 58,674 women were followed for 142,475 women-years of observation. Loss to follow-up was 2.4%. Serious adverse and fatal events were rare, and rate ratios were close to unity (1.0). Cox regression analysis of cardiovascular outcomes yielded hazard ratios for DRSP-containing vs. LNG-containing and other OCs of 1.0 and 0.8 (upper 95% confidence limits, 1.8 and 1.3) for venous, and 0.3 and 0.3 (upper 95% confidence limits, 1.2 and 1.5) for arterial thromboembolism, respectively. CONCLUSIONS: Risks of adverse cardiovascular and other serious events in users of a DRSP-containing OC are similar to those associated with the use of other OCs.

Breast cancer risk associated with different HRT formulations: a register-based case-control study.

BACKGROUND: Previous epidemiological studies have inconsistently shown a modestly increased breast cancer risk associated with hormone replacement therapy (HRT). Limited information is available about different formulations--particularly concerning different progestins. METHODS: A case-control study was performed within Germany in collaboration with regional cancer registries and tumor centers. Up to 5 controls were matched breast cancer cases. Conditional logistic regression analysis was applied to estimate crude and adjusted odds ratios (OR) and 95% confidence intervals (95% CI). Stratified analyses were performed to compare the risk of different estrogens, progestins, and combinations. RESULTS: A total of 3593 cases of breast cancer were identified and compared with 9098 controls. The adjusted overall risk estimate for breast cancer (BC) associated with current or past use of HRT was 1.2 (1.1-1.3), and almost identical for lag times from 6 months to 6 years prior to diagnosis. No significant trend of increasing BC risk was found with increasing duration of HRT use, or time since first or last use in aggregate. Many established BC risk factors significantly modified the effect of HRT on BC risk, particularly first-degree family history of BC, higher age, lower education, higher body mass index (BMI), and never having used oral contraceptives (OCs) during lifetime. Whereas the overall risk estimates were stable, the numbers in many of the sub-analyses of HRT formulation groups (estrogens, progestins, and combinations) were too small for strong conclusions. Nevertheless, the BC risk seems not to vary much across HRT formulation subgroups. In particular, no substantial difference in BC risk was observed between HRT containing conjugated equine estrogens (CEE) or medroxyprogesterone acetate (MPA) and other formulations more common in Europe. CONCLUSION: The BC risk of HRT use is rather small. Low risk estimates for BC and a high potential for residual confounding and bias in this observational study do not permit causal conclusions. Apparently, there is not much variation of the BC risk across HRT formulations (estrogens, progestins). However, the small numbers and the overlapping nature of some of the subgroups suggest cautious interpretation.

Quality of life and hormone use: new validation results of MRS scale.

BACKGROUND: The Menopause Rating Scale is a health-related Quality of Life scale developed in the early 1990s and step-by-step validated since then. Recently the MRS scale was validated as outcomes measure for hormone therapy. The suspicion however was expressed that the data were too optimistic due to methodological problems of the study. A new study became available to check how founded this suspicion was. METHOD: An open post-marketing study of 3282 women with pre- and post- treatment data of the self-administered version of the MRS scale was analyzed to evaluate the capacity of the scale to detect hormone treatment related effects with the MRS scale. The main results were then compared with the old study where the interview-based version of the MRS scale was used. RESULTS: The hormone-therapy related improvement of complaints relative to the baseline score was about or less than 30% in total or domain scores, whereas it exceeded 30% improvement in the old study. Similarly, the relative improvement after therapy, stratified by the degree of severity at baseline, was lower in the new than in the old study, but had the same slope. Although we cannot exclude different treatment effects with the study method used, this supports our hypothesis that the individual MRS interviews performed by the physician biased the results towards over-estimation of the treatment effects. This hypothesis is underlined by the degree of concordance of physician's assessment and patient's perception of treatment success (MRS results): Sensitivity (correct prediction of the positive assessment by the treating physician) of the MRS and specificity (correct prediction of a negative assessment by the physician) were lower than the results obtained with the interview-based MRS scale in the previous publication. CONCLUSION: The study confirmed evidence for the capacity of the MRS scale to measure treatment effects on quality of life across the full range of severity of complaints before treatment. The difference of the relative improvement after therapy between the old and current study as well as the observed different sensitivity/specificity is--as a matter of probability--more likely to be caused by a bias introduced by the different application of the MRS scale than by real differences in the efficacy of the therapy. A randomized clinical trial would be needed to test the impact of the latter. The message for future studies is: The MRS scale should be only used as self-administered tool where the suggestive effect of questions raised by health professionals ("therapeutic optimism") can be largely excluded.

Sensitivity as outcome measure of androgen replacement: the AMS scale.

BACKGROUND: The capacity of the AMS scale as clinical utility and as outcome measure still needs validation. METHODS: An open post-marketing study was performed by office-based physicians in Germany in 2004. We analysed data of 1670 androgen-deficient males who were treated with testosterone gel. The AMS scale was applied prior to and after 3 months treatment. RESULTS: The improvement of complaints under treatment relative to the baseline score was 30.7% (total score), 27.3% (psychological domain), 30.5% (somatic domain), and 30.7% (sexual domain), respectively. Patients with little or no symptoms before therapy improved by 9%, those with mild complaints at entry by 24%, with moderate by 32%, and with severe symptoms by 39% - compared with the baseline score. We showed that the distribution of complaints of testosterone deficient men before therapy almost returned to norm values after 12 weeks of testosterone treatment. Age, BMI, and total testosterone level at baseline did not modify the positive effect of androgen therapy. We also demonstrated that the AMS results can predict the independent (physician's) opinion about the individual treatment effect. Both, sensitivity (correct prediction of a positive assessment by the physician) and specificity (correct prediction of a negative assessment by the physician) were over 70%, if about 22% improvement of the AMS total score was used as cut-off point. CONCLUSION: The AMS scale showed a convincing ability to measure treatment effects on quality of life across the full range of severity of complaints. Effect modification by other variables at baseline was not observed. In addition, results of the scale can predict the subjective clinical expert opinion on the treatment efficiency.

European active surveillance study of women taking HRT (EURAS-HRT): study protocol [NCT00214903].

BACKGROUND: The post marketing safety surveillance program for a drug containing a new chemical entity should assess both, the safety outcomes that relate specifically to the targeted population, as well as those that could potentially be related to special pharmacological characteristics of the drug. Active safety surveillance using valid epidemiological study designs has been proven to be a pertinent and reliable method to approach this endeavor. METHODS/DESIGN: The primary objective of the study is to compare incidence rates of serious adverse events in users of all types of newly prescribed oral HRT products. This active surveillance study will assess pertinent cardiovascular outcomes--in particular venous and arterial thromboembolism--and other serious adverse events (SAEs) in new HRT users over a period of several years. One product under surveillance is Angeliq, which contains the novel progestagen drospirenone (DRSP) combined with estradiol. In addition, all other oral combined HRT products with a novel progestagen or estrogen that will be newly marketed during the study period will be studied. These new HRT products will be compared with established HRT products. The combined cohort will include at least 30,000 women recruited in several European countries. At least 90,000 years of observation are expected from the field work which started in early 2002 and will end around 2008. The participating women will complete a baseline survey using a self-administered questionnaire to describe the baseline risk. After 6 months, 12 months, and then on an annual basis, they will fill out a questionnaire in which they record complaints and events during the use of the prescribed HRTs. All adverse outcomes occurring during the observational period will be evaluated. DISCUSSION: A complete lifetime medical history, individually validated SAEs over time, and a low loss to follow-up rate are essential for a robust safety assessment. Therefore, the lifetime history of diseases and relevant medications will be documented. Reported SAEs will be validated and analyzed. A four level, multi-faceted follow-up process was established to ensure low loss to follow-up rates (e.g., 3-5% after three years of follow up). Multivariate methods will be used to adjust for confounding.

Case-control study on analgesics and nephropathy (SAN): protocol.

BACKGROUND: The association between intake of non-phenacetin-containing analgesics and the occurrence of chronic renal failure is still controversially discussed. A new epidemiologic study was planned and conducted in Germany and Austria. METHODS/DESIGN: The objective of the international, multicenter case-control study was to evaluate the association between end-stage renal disease (ESRD) and use of non-phenacetin-containing analgesics with particular emphasis on combined formulations. A targeted sample of 1000 new (incident) dialysis patients, aged less than 50 years, was planned to recruit between January 1, 2001 and December 31, 2004. The age limit was chosen to avoid contamination of the study population with phenacetin-containing analgesics to the extent possible. Four control subjects per ESRD case, matched by age, sex, and region were selected from the population living in the region the case came from. Lifetime exposure to analgesics and potential renal risk factors were recorded in a single face-to-face interview. A set of aids was introduced to reinforce the memory of study participants. A standardized, pre-tested interview questionnaire (participants), a medical documentation sheet (physicians in dialysis centres), a logbook for all activities (dialysis centres) were used to collect the necessary data. Quality management consisted of the standardized procedures, (re-) training and supervision of interviewers, regular checks of all incoming data for completeness and plausibility. The study is scientifically independent and governed by a international Scientific Advisory Committee that bridged the gap between the sponsoring companies and the investigators. Also other advisory groups assisted the managing committee of the study. All relevant German and Austrian nephrological associations supported the study, and the study design was carefully reviewed and approved by the Kidney Foundation of Germany. DISCUSSION: The study is expected to answer the main research question by end 2005. There is however a high potential for various biases that we tried to address with adequate measure. One limitation however cannot be overcome: The methodologically needed age-limitation of the study will make it not easy to generalize the results to age groups over 50 years. It might be suggested to repeat the study for persons over 50 years in 10 years when contamination with phenacetin use early in life is likely to be outgrown.

Comparison of incidence/risk of venous thromboembolism (VTE) among selected clinical and hereditary risk markers: a community-based cohort study.

BACKGROUND: Little information is available from community-based long-term VTE cohort studies to compare the absolute thrombosis risk of established clinical and genetic risk factors. MATERIALS AND METHODS: The occurrence of venous thromboembolism (VTE) was observed during a 10-year observation period in the BAvarian ThromboEmbolic Risk (BATER) study, a cohort study of 4337 women (age 18-55 years). We collected data on demographics, reproductive life, lifestyle, conditions/diseases, and particularly potential risk factors for VTE with a self-administered questionnaire. The objective was to present incidence rates of VTE and to show relative risk estimated associated with different clinical and genetic risk factors. RESULTS: 34 new, by diagnostic means confirmed VTE events occurred during the observation time of 32,656 women-years (WY). The overall incidence of VTE was 10.4 per 10(4) WY. The incidence rates varied markedly among different risk cohorts. The highest incidence was observed in women with previous history of VTE, followed by family history of VTE. None of the measured "genetically-related risk markers" (antithrombin, protein C, FVL, prothrombin mutation, or MTHFR) showed a significant VTE risk. CONCLUSION: Most of the discussed VTE risk factors showed no significant association with the occurrence of new VTEs due to smallness of numbers. Only first-degree family history of VTE and own history of a previous VTE event depicted a significant association with future VTE. Clinical information seems to be more important to determine future VTE risk than genetically related laboratory tests.