Aging Males' Symptoms scale: a standardized instrument for the practice.

The Aging Males' Symptoms (AMS) scale was designed and standardized as self-administered scale (a) to assess symptoms of aging (independent from those which are disease-related) among groups of males under different conditions, (b) to evaluate the severity of symptoms over time, and (c) to measure changes pre- and post-androgen replacement therapy. It is a short and easy to apply instrument, it has a very simple evaluation scheme, and was internationally well accepted (translated into over 20 languages). Methodological test characteristics are: a) reliability measures: (internal consistency and test-retest stability) were found to be good across countries, b) validity: the internal structure of the AMS in healthy and androgen deficient males and across countries was sufficiently similar to conclude that the scale really measures the same phenomenon across all age groups. The comparison of the AMS with the two established screening instruments for androgen deficiency showed sufficiently good compatibility. Consequently, a screening tool for hypogonadism was developed, consisting of the AMS scale, body mass index (BMI) and age. The test characteristics of this screening tool (sensitivity and specificity) are promising. Clinicians often consider validity as utility for outcome measurement. The AMS scale showed a convincing ability to measure treatment effects on quality of life across the full range of severity of complaints before therapy. The distribution of complaints of testosterone deficient men before therapy almost returned to normal values after 12 weeks of testosterone treatment.

Harmonized Italian version of the Aging Males' Symptoms scale.

INTRODUCTION: The interest in clinical investigations in health-related quality of life (HRQoL) of aging men has increased over recent years, particularly in the context of partial androgen deficiency. The aim of this paper is to inform the scientific community about a harmonized Italian Aging Males' Symptoms (AMS) scale. METHODS: There were two slightly different Italian AMS scales, which both underwent an up-to-date linguistic & cultural translation process, i.e., were both valid to be applied in clinical research. However, there are potential long-term problems associated with having two Italian language versions of the scale in the same country. Therefore, an ad hoc committee of key persons related to both versions met with the scale's developer, to create a harmonized single Italian AMS. RESULTS: The harmonization meeting came up with a consensus item-by-item and the new Italian reference scale was agreed upon. It was decided that this scale should be published to avoid any confusion among future users. CONCLUSION: The Italian AMS scale published in this paper should be used for future clinical and other research.

Composite screener for androgen deficiency related to the Aging Males' Symptoms scale.

OBJECTIVE: Methodological characteristics of the Aging Males' Symptoms (AMS) scale point towards a high standard measurement and comparison of health-related quality of life (HRQoL) over time or intervention. However, the scale was neither developed nor standardized as a screening instrument for androgen deficiency. METHODS: Data of the Austrian ANDROX study suggested to develop a composite screener for androgen deficiency based on AMS, age, and BMI, to determine sensitivity and specificity to detect low total testosterone (TT) levels. The findings were compared with those of an independent sample of urological patients with suspicion of androgen deficiency (AD) from Germany (n = 803). RESULTS: A graphical solution for a composite-screening tool was proposed, with three levels of suspicion for AD: positive screening result (high suspicion), equivocal result, and negative screening result (no suspicion, AD unlikely). The percentage of TT values < 4 ng/ml were 18.7%, 40.7% and 58.8% in the three categories: negative, equivocal and positive, respectively. The findings were confirmed in the independent German sample. In both instances, neither sensitivity nor specificity was very high, i.e., between about 50% and 75%. CONCLUSION: The results of the development and initial validation of the new screener are promising. Further information, and experience from the practice, is needed to confirm or refute the hypothesis that this screener is a useful tool for medical practice.

Can results of the Aging Males' Symptoms (AMS) scale predict those of screening scales for androgen deficiency?

INTRODUCTION: The Aging Male Symptoms' (AMS) scale was designed as a health-related quality of life (QoL) scale and standardized as a self-administered scale, first, to assess symptoms of aging (independent from those which are disease-related) between groups of males under different conditions, second, to evaluate the severity of symptoms/QoL over time, and, third, to measure changes pre- and post-androgen replacement therapy. The scale is in widespread use (17 languages currently available) and a recent review of methodological data documented good psychometric characteristics and ability as a clinical utility. This paper describes test characteristics of the AMS (positive and negative predictive values), taking two internationally established and published screening scales for androgen deficiency as the available standard. METHOD: A sample of 150 German males aged 40-69 years completed the AMS scale and two screening scales for androgen deficiency: the ADAM scale of Morley and colleagues and the screener of Smith and colleagues. The technique of a computer-assisted telephone interview was applied. RESULT: The comparison of the AMS with the two screening instruments for androgen deficiency showed sufficiently good compatibility despite conceptual differences. The AMS scale sufficiently predicted the results of the two screening instruments. A positive predictive value of 92% and a negative predictive value of 50% were found regarding the ADAM scale. The respective figures regarding Smith's screener were 65% and 49% for positive and negative predictive values, respectively. CONCLUSION: The AMS scale obviously measures a similar phenomenon as the two established and widely used screeners for androgen deficiency, although it was not developed as a screening instrument.

Harmonized French version of the Aging Males' Symptoms Scale.

Interest in clinical investigations about the health-related quality of life (HRQoL) of aging men has increased in recent years. The aim of this paper is to inform the scientific community about a harmonized French Aging Males' Symptoms (AMS) Scale. There were two slightly different French AMS Scales, which both underwent an up-to-date linguistic and cultural translation process, i.e. were valid to be applied in research. However, it was felt to be unfortunate that two versions of one language in one country existed. Therefore, an ad hoc committee of both translation teams were asked to develop a harmonized single French AMS Scale. The harmonization meeting developed a consensus item-by-item and the new French reference scale was agreed upon. It was agreed that only this scale should be published to avoid confusion among future users. The French AMS Scale published in this paper should be used for future research and necessary cultural/linguistic adaptations in the French-speaking world.

The association between extrinsic activated protein C resistance and venous thromboembolism in women.

Recently, discussions have focused on the question of whether acquired APC resistance (APCsr) is a clue to the observed association between risk of venous thromboembolism (VTE) and OC use especially with the so-called third-generation OCs. It seems plausible that abnormalities in an extrinsic-based APCsr reflect an increased risk of VTE in women, but this has not yet been properly studied. The objective of our study was to determine whether there was an association of extrinsic APC resistance with VTE risk in a case-control study. Sixty-seven women with confirmed VTE diagnosis were consecutively recruited in primary health care settings, interviewed and blood samples were taken at least 6 months after VTE. Cases were age-matched to 290 population controls. Extrinsic APC resistance was measured as normalized APC ratio (APCsr). The effect of APC on tissue factor-initiated thrombin generation was measured in plasma using alpha2-macroglobulin attached thrombin activity as an endpoint. The extrinsic APCsr was significantly associated with factor V Leiden (FVL) mutation, both in the cases and in the controls. Also, in the women using OC, significantly higher values of APCsr were observed, which confirms the results of other studies. We did not identify a significant association between the extrinsic APCsr and VTE in women not using OC who are non-carriers of factor V Leiden using different approaches: comparison of medians, analyses with unconditional logistic regression using various cut-points of the APCsr distribution, and the comparison between the highest and the lowest quartile of APCsr. With all attempts, the risk estimates were close to unity. In conclusion, we were not able to find evidence for any association of extrinsic APCsr with VTE in women who were not using OCs and non-carriers of FVL.

[Reliability of the Menopause Rating Scale (MRS): Investigation in the German population]. / Reliabilität der Menopause-Rating-Skala (MRS) - Untersuchung für die deutsche Bevölkerung.

The Menopause Rating Scale (MRS) is a well accepted instrument to measure the severity of menopausal symptoms. As yet, however, investigations had not specifically been directed towards short-term test-retest reliability of the scale. The MRS was twice applied in a random sample of 45-65 years aged women of the German Cohort Study of Women's Health with a distance between the measurements of 14 days. The response rate in the sample was 70 %. The correlation coefficient (Pearson) of the sum-score of the two measurements was r = 0.82. The high repeatability of the test results confirms our clinical experience and emphasizes excellent practical applicability. The MRS can be recommended for the clinical practice as a reliable scale both for the measurement and long-term surveillance of menopausal complaint dynamics.

[Trends of OC use 1980-1999 in a German cohort of women]. / Trend der OC-Nutzung in einer Deutschen Frauen-Kohorte 1980-1999 - Ergebnisse der Deutschen Kohortenstudie zur Frauengesundheit.

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.

[Frequency and reasons for switching/stopping use of oral contraceptives. Results of the German Cohort Study on Women Health]. / Gründe und Häufigkeit von Wechsel/Stopp der Einnahme oraler Kontrazeptiva. Ergebnisse der Deutschen Kohortenstudie zur Frauengesundheit.

Frequency and reasons for switching/stopping use of oral contraceptives. Results of the German Cohort Study on Women Health. Use of oral contraceptives is the safest and most commonly used method of contraception. The frequency of use underscores the importance of research on benefits, risks, and acceptability of long-term use. - An interim analysis of the German Cohort Study on Women's Health (aged 15-65 years) was performed to analyse frequency and reason of switching or stop of OC-use. We got for this analysis over 10 000 women with almost 100 000 years of observation from first to last (or current) OC use. - The prevalence of ever use of OCs was 85.5 % in our cohort. Switching or stop of OC use was observed in 93 % of the women. The frequency of switching increased with age and duration of use. Social parameter such as education, employment status, and living in the old or the new Federal States were not materially associated with the frequency of switching or stopping OC use. Satisfaction with general health, psychic stability, and sexual life was slightly associated with the frequency of switching: The better satisfaction the lower frequency of switching, but the sequence of cause and consequence is unclear. The most frequent categories of reasons for switching were observed side effects and personal reasons. Desire to get pregnant was the number one single reason, followed by headache/migraine, and bleeding problems. The frequency of more than 50 single reasons is listed. - The frequency and the knowledge of reason for switching or stopping OC use underlines the need for a good collaboration between physician and treated woman. However, also research on long-term compliance is required and the development of OCs with even less side effects.

[Reasons for the change in HRT therapy from the perspective of women. Results of the German Cohort Study on Women's Health]. / Gründe für eine Veränderung der HRT-Therapie aus der Sicht der Frauen. Ergebnisse der Deutschen Kohortenstudie zur Frauengesundheit.

Acceptance and reasons for changing the HRT play an important role against the background of the efficiency of the therapy and increasing life expectancy. Women in developed, industrialized countries live about one-third of their lives in the peri- and postmenopausal phases.--The frequency of switching and the reasons were examined in an interim analysis of the German cohort study on women's health. This historical analysis was based on over 10,000 women (i.e. about 300,000 man-years of observation), of whom 2,002 women (aged 40-65) were constant users of HRT.--The prevalence of use and the frequency of switching to other HRT preparations were somewhat higher in women above 60 as compared to those aged 40-59. The duration of use had no impact on the prevalence of use or the frequency of switching or cessation. Neither education nor the past use of oral contraceptives showed a clear association with the frequency of switching. The most frequent reasons for switching or cessation were adverse events, i.e. reasons independent of age. Women aged from 40 to 49 more frequently reported weight gains, menstrual disturbances, headaches, and impaired well-being than did older women. A recurrence of menstruation was more frequently reported by women over 60 as the reason for switching or discontinuing HRT.--The knowledge of the reasons for women switching or discontinuing HRT underlines the importance of close collaboration between women and their gynaecologists, as well as that of intensified research for optimal products.

Relationship between nonphenacetin combined analgesics and nephropathy: a review. Ad Hoc Committee of the International Study Group on Analgesics and Nephropathy.

BACKGROUND: The debate on the association between nonphenacetin-containing combined analgesics and renal disease has lasted for several years. METHOD: A peer review committee of scientists, selected jointly by the regulatory authorities of Germany, Switzerland, and Austria and the pharmaceutical industry was asked to critically review data on the relationship between nonphenacetin combined analgesics and nephropathy. RESULTS: The committee regarded epidemiologic evidence on nonphenacetin combined analgesics as inconclusive because of sparse information and substantial methodological problems. The committee also noted that a diagnosis of analgesic-associated nephropathy (AAN) in clinical practice usually depends on information about exposure before or in the early stages of the disease and is seldom accompanied by specific histologic evidence. The morphologic finding of papillary calcification can arise from other conditions and is not specific for AAN. For these reasons, the identification criteria for AAN should be reappraised with scientific methods to validate the diagnostic procedure. In the limited amount of experimental pharmacological data in humans and animals, the committee found no convincing evidence to confirm or refute the hypothesis that nonphenacetin combined analgesics are more nephrotoxic than single formulations. For caffeine taken with combined analgesics, the currently available information is not sufficient to postulate a harmful toxicological effect. CONCLUSION: The committee's two main conclusions were that sufficient evidence is absent to associate nonphenacetin combined analgesics with nephropathy and that new studies should be done to provide appropriate data for resolving the question.

Venous thromboembolism and oral contraceptive use: a methodological study of diagnostic suspicion and referral bias.

BACKGROUND: In studies of oral contraceptive oral contraceptive use and risk of venous thromboembolism, bias related to heightened diagnostic suspicion and preferential referral of oral contraceptive users has been an issue. The aim of our study was to determine the presence and potential impact of diagnostic suspicion and referral bias. METHODS: We conducted a case/non-case study in 21 regional study centers in Germany and, in parallel, a conventional case-control study using the same cases but randomly selected population controls from the same areas. Women with symptoms compatible with venous thromboembolism were included in the study between 1994 and 1999, and classified as cases or non-cases (first reference group) according to the diagnostic work-up (case/non-case study). A second reference group consisted ofpopulation controls (conventional case-control study as an internal comparison for the case/non-case study): 606 cases, 462 non-cases and 2942 population controls aged 15-49 years. Adjusted unconditional regression analyses were performed. RESULTS: Adjusted odds ratios for venous thromboembolism in oral contraceptive users were systematically higher in the classical case-control study compared to the case/non-case approach (using the same cases) across all subgroup analyses (e.g. for idiopathic cases, the odds ratio was 67% higher in the case-control study: 4.33 (95% confidence interval (CI) 3.27-5.74) versus 2.60 (95% CI 1.75-3.88)). We found a significantly increasing trend of oral contraceptive use in four categories of increasingly sophisticated diagnostic tests that were applied to 1067 women with a suspicion of venous thromboembolism, irrespective of the outcome. Stratified analysis showed the diagnostic level to be a confounder. CONCLUSION: In our population-based study with the possibility of internal comparison, we found clear evidence that diagnostic suspicion and referral bias does play an important role in case-control studies of venous thromboembolism risk among oral contraceptive users. This underlines the importance of making an effort to avoid this bias when designing a new study.

Do caffeine-containing analgesics promote dependence? A review and evaluation.

OBJECTIVE: Debates about the suspected association between kidney disease and use of analgesics have led to concern about whether caffeine could stimulate an undesirable overuse of phenacetin-free combined analgesics. A committee was asked to critically review the pertinent literature and to suggest guides for clinical practice and for consideration of international regulatory authorities. PARTICIPANTS: A group of international scientists, jointly selected by the regulatory authorities of Germany, Switzerland, and Austria and the pharmaceutical industry. EVIDENCE: All invited experts evaluated relevant literature and reports and added further information and comments. CONCLUSIONS: Caffeine has a synergistic effectiveness with analgesics. Although caffeine has a dependence potential, the potential is low. Experimental data regarding dependence potential for caffeine alone may not correspond to the conditions in patients with pain. Withdrawal is not likely to cause stimulation or sustainment of analgesic intake. For drug-induced headache, no single or combined analgesic was consistently identified as causative, and no evidence exists for a special role of caffeine. Strong dependence behavior was observed only in patients using phenacetin-containing preparations, coformulated with antipyretics/analgesics and caffeine. This finding may have led to the impression that caffeine stimulates overuse of analgesics. SUMMARY: Although more experimental and long-term data would be desirable to show possible mechanisms of dependence and to offer unequivocal proof of safety, the committee concluded that the available evidence does not support the claim that analgesics coformulated with caffeine, in the absence of phenacetin, stimulate or sustain overuse.

Emerging evidence on oral contraceptives and arterial disease.

A number of case-control studies published in recent years have shown an apparent increase in the risk of venous thromboembolism (VTE) associated with the use of third-generation oral contraceptives (OCs) compared with second-generation OCs. However, it is thought that these studies were subject to a number of biases that would have increased the risk estimates for third-generation OCs while lowering those for second-generation preparations. Data on the risk of ischemic stroke and myocardial infarction (MI) show no such difference between generations of OCs, with a statistically significant reduction in the risk of acute MI from first- to third-generation in one major study. Available results indicate that there is no significant increase in the risk of ischemic stroke or acute MI associated with the use of low-dose estrogen OCs in young women who are properly screened before use, and who have no pre-existing cardiovascular risk factors, such as smoking and hypertension, for these conditions. These findings should be taken into account when interpreting the results of studies on the risk of VTE in women taking combined OCs.

Occupational exposure and liver cancer in women: results of the Multicentre International Liver Tumour Study (MILTS).

The association of occupational variables and hepatocellular cancer (HCC) is discussed with particular reference to women, as little research has been undertaken on their behalf. This paper reports the results of an international case-control study concerning women and involves 317 cases of HCC and 1789 controls. Working in the chemical industry was shown to have only a marginally significant risk associated with HCC: adjusted odds ratio (OR) and 95% confidence interval 2.37 (1.04-5.41). Other non-significantly elevated ORs were observed in the pharmaceutical, plastics, PVC-producing, farming and butchery industries. Little consistency was found among the risk estimates for HCC, based on three different analytical approaches. None of the analyses showed a linear trend of risk with increasing duration of exposure. However, the numbers of exposed cases and controls were small for many of the occupations and therefore the study power and precision were low. We failed to find important and consistent evidence for a relationship between HCC in women and occupational variables. However, even weak evidence of occupational risk warrants careful consideration in future studies.

Are factor V Leiden carriers who use oral contraceptives at extreme risk for venous thromboembolism?

BACKGROUND: Major concern was raised by an earlier study regarding oral contraceptive use in women with the factor V Leiden mutation. A more than 30-fold increase in relative risk for venous thromboembolism was reported; for homozygotes, the relative risk was as much as 100-fold or more. OBJECTIVE: To replicate the reported risk estimates with a new population-based case-control study. METHODS: Eighty women with a diagnosis of venous thromboembolism were consecutively identified and compared with population-based controls (n = 406). Factor V Leiden mutation was identified by genotype analysis. The evaluation was performed with conditional logistic regression (matched for 5-year age group). RESULTS: Matched, adjusted odds ratios (OR) for idiopathic venous thromboembolism in women without and with the factor V Leiden mutation who used oral contraceptives were 4.1 (95% confidence interval (CI) 2.1-7.8) and 10.2 (95% CI 1.2-88.4), respectively. The adjusted OR for factor V Leiden carriers was 2.0 (95% CI 1.0-4.4). The OR for women with the factor V Leiden mutation and oral contraceptive use versus no factor V Leiden mutation and no oral contraceptive use was 10.2 (95% CI 3.8-27.6). CONCLUSION: The results confirm the increased relative risk of idiopathic venous thromboembolism for users of oral contraceptives and factor V Leiden carriers. However, we suspect that the true risk for women who are factor V Leiden carriers may be increased two- to four-fold rather than seven-fold or more, and that the risk for the combination of factor V Leiden and oral contraceptive use may be increased in the order often- to 15-fold rather than over 30-fold.

[The Menopause Rating Scale (MRS II): methodological standardization in the German population]. / Menopause-Rating-Skala (MRS II): Methodische Standardisierung in der deutschen Bevölkerung.

The Menopause-Rating-Scale (MRS I) was used in clinical practice since 1992. The physician had to document the severity of 10 important estrogen-related climacteric symptoms. Practical experience and a critical methodological evaluation justified a revision: The MRS I should be converted into a self-administrative rating scale, the wording somewhat optimized, the layout adjusted and one item added. The standardization of the new scale (MRS II) was performed in a representative sample of the German population aged 45-60 years. Three dimensions were extracted from the menopausal symptoms using multivariate statistical techniques: somato-vegetative, psychological, and urogenital complexes of symptoms. A simple evaluation scheme was developed for the MRS II by summing up scoring points. Reference values for the frequency of 4 levels of intensity of complaints in the population were defined and provided for purposes of comparison. The MRS II meets a high methodological standard as an instrument standardized in the population. Moreover, it is convenient to apply this instrument in daily practice in order to quantitate variation of menopausal complaints.

[Non-contraceptive benefits of the pill--an often neglected fact]. / Nicht-kontrazeptiver Nutzen der Pille--ein oft unbeachteter Fakt.

While rare cardiovascular risks of oral contraceptives (OCs) caused a lot of concern among OC-using women in the recent past, little attention has been paid in the public to the non-contraceptive benefits of OCs. Short, medium and long term non-contraceptive benefits have to be considered. The early Anglo-American cohort and case-control studies demonstrated a reduction of menstrual complaints, iron-deficiency anaemia, ectopic pregnancies, and a partly drastic reduction of some benign and malignant tumours such as endometrial and ovarian cancer. A risk reduction of rheumatoid arthritis is discussed controversially. The present paper gives an overview of the state of knowledge. For newer OCs with different composition, comparable studies are lacking. Therefore, a cohort study was initiated in Germany in April 1998 to investigate these associations as well for newer OCs, which is presented. The described non-contraceptive benefits should be considered in the benefit-risk assessment when prescribing OCs.

[German Cohort Study of Women's Health--benefits of oral contraceptives. Study protocol]. / Die Deutsche Kohortenstudie zur Frauengesundheit--Zum Nutzen von oralen Kontrazeptiva. Ausführungen zum Studienprotokoll.

This publication is about the study protocol of the German Cohort Study on Women's Health. The main objective is to investigate medical benefits of a long-term oral contraceptive use. The design is an analytical cohort study based on inquiries. Additional cases will be recruited to analyse rare events in separate case-control studies. Voluntary participants who signed to participate in a long-term study are included. An annual drop-out rate of 15% is expected. Study variables encompass personal characteristics, lifetime history of diseases, but also disturbances of the state of health, and quality of life. It is anticipated to achieve 400,000 women-years of observation by 2001 (historic and concurrent follow-up). The study started April 1, 1998 and the current financial phase finishes December 31, 2001. 6000 participants were recruited until December 1998 equivalent to about 190,000 observation-years. Until the end of 1999, an additional 70,000 women-years should be included. There have been many suggestions from participants' to include additional issues of women's health into the study.

[The Bavarian Thromboembolic Risk Cohort Study (BATER). Study protocol, state of the investigation and first results]. / Die bayerische Thromboembolierisiko-Kohortenstudie (BATER). Studienprotokoll, Stand der Untersuchung und erste Ergebnisse.

OBJECTIVE: Familiar venous thromboembolic disease (VTE) is known to be related with factor V Leiden mutation (FVL), but also with other genetic markers. It is the objective to investigate of the BATER-study in a representative Bavarian cohort, and to assess whether they could predict VTE events. This paper shortly describes the study protocol, gives an overview of planned sub-studies, and provides first results of the historic cohort analysis. PATIENTS AND METHODS: The baseline survey of the cohort study of Bavarian women aged 18-49 years (random sample from the population) was performed in two samples in 1996 and 1997. It was planned to estimate a prevalence and predictive value of potential markers of VTE in a historic--prospective as well as concurrent approach with annual follow-up of the cohort. This representative cohort should build a basis for nested case-control studies and serve as a reference group for other analytical epidemiological studies in young women. 1685 women were ascertained (response rate 61%), underwent an inquiry, and provided blood samples for a blood bank; for this paper, complete data are available from 1650 women. Laboratory parameters were measured to determine APC resistance, FVL-mutation, antithrombin-, protein C and S deficiency, and were correlated to the results of a detailed, life-time history of thrombembolic events. RESULTS: The prevalence of FVL mutation in the sample was 5.7% (95% confidence interval 4.6-6.6%). Other genetic VTE risk markers were observed to be less frequent than 1%. The positive predictive value (pPV) of FVL mutation for a VTE event is about 7%, but for a positive family history of VTE (first grade relatives) 3% only. CONCLUSIONS: VTE events are rare in the German population of young women, even in cases of FVL mutation. A positive family history is rarely associated with the occurrence of VTE in women under 50 years of age, and the predictive value of FVL mutation is low. Therefore, a screening for FVL mutation is not justified unless there is suspicion of a high VTE risk for other reasons.