Accelerated menopausal changes as human disease model 'FOCUM' for the development of osteoarthritis and other degenerative disorders: protocol for a prospective cohort study.

INTRODUCTION: The incidence of degenerative disorders, including osteoarthritis (OA), increases rapidly in women after menopause. However, the influence of the menopause is still insufficiently investigated due to the slowness of menopausal transition. In this study, a novel human model is used in which it is expected that menopausal-related changes will occur faster. This is the Females discontinuing Oral Contraceptives Use at Menopausal age model. The ultimate aim is to link these changes to OA and other degenerative disorders, including cardiovascular diseases, diabetes, osteoporosis and tendinopathies. METHODS AND ANALYSIS: This is a pilot observational prospective cohort study with 2 years of follow-up. Fifty women aged 50-60 who use oral contraceptive (OC) and have the intention to stop are included. Measurements are performed once before stopping OC, and four times thereafter at 6 weeks, 6 months, 1 year and 2 years. At every time point, a questionnaire is filled in and a sample of blood is drawn. At the first and final time points, a physical examination, hand radiographs and a MRI scan of one knee are performed. The primary OA outcome is progression of the MRI Osteoarthritis Knee Score. Secondary OA outcomes are the development of clinical knee and hand OA, development of knee OA according to the MRI definition, and progression of radiographic features for hand OA. Principal component analysis will be used to assess which changes occur after stopping OC. Univariate and multivariate generalised estimating equation models will be used to test for associations between these components and OA. ETHICS AND DISSEMINATION: The study has been approved by the Medical Ethics Committee of the Erasmus MC University Medical Center Rotterdam (MEC-2019-0592). All participants must give informed consent before data collection. Results will be disseminated in national and international journals. TRIAL REGISTRATION NUMBER: NL70796.078.19.

Are lower urinary tract symptoms associated with cardiovascular disease in the Dutch general population? Results from the Krimpen study.

PURPOSE: To describe the association between lower urinary tract symptoms (LUTS) and cardiovascular diseases (CVD), with adjustment for age and other confounders. We were specifically interested in the possible predictive value of LUTS to the incidence of CVD in the future in the general population. METHODS: We performed post hoc analyses using data from the Krimpen study, a large community-based study in the Netherlands. All men aged 50-75 years, without prostate or bladder cancer, a history of radical prostatectomy, or neurogenic bladder disease, were invited to participate for a response rate of 50%. At baseline, 1,610 men were included. CVD status was compared to LUTS category, using logistic regression, providing odds ratios with 95% confidence intervals (OR 95% CI). For the longitudinal analyses in men without CVD at baseline, hazard ratios (HR) and 95% CI were estimated using Cox proportional hazard models with the occurrence of a CVD as outcome variable. RESULTS: At baseline, 362 men (22%) had a history of CVD. The ORs for CVD for men with moderate to severe LUTS were 2.04 (unadjusted, 95% CI 1.58-2.63), 1.86 (1.43-2.41, adjusted for age), and 1.81 (1.38-2.37, adjusted for age and other confounders). Of the 1,248 CVD-free men, 58 (4.6%) had a CVD event. HRs for moderate to severe LUTS were 0.98 (95% CI 0.52-1.86, unadjusted) and 1.08 (0.57-2.07, adjusted for age, obesity, hypertension, and erectile dysfunction). CONCLUSIONS: The cross-sectional analyses revealed a clear correlation between moderate to severe LUTS and CVD. In longitudinal analyses, however, no significant association was shown.

Erectile dysfunction in the community: trends over time in incidence, prevalence, GP consultation and medication use--the Krimpen study: trends in ED.

INTRODUCTION: In the general population, erectile dysfunction (ED) is surrounded by a "taboo." Epidemiologists studying this problem have to be aware of the phenomenon of the "tip-of-the-iceberg." AIMS: Our aim is to describe the iceberg phenomenon for ED and their help-seeking behavior in the general population during a period when public interest in ED heightened and waned after the introduction of the drug sildenafil. METHODS: The data were obtained as part of a large longitudinal community-based study, i.e., the Krimpen study. With four rounds of data collection with an approximate 2.1 years interval, the local pharmacists provided data on medication use, whereas abstracts from the medical record and history were provided by the local general practitioners (GPs). The data from the questionnaires were entered into the Krimpen study database but were not communicated to the GPs. MAIN OUTCOME MEASURES: ED: according to the ICS-questionnaire, GP consultation: search of electronic medical dossier for ED or reports from any specialist, use of ED medication as delivered by the pharmacy. RESULTS: The age-standardized prevalence of ED is stable, i.e., around 40%. During the period 1995 to 2000, the incidence increased from 5% to 6.5%, then it stabilizes around 5% per year. The first-time use of ED medication increases exponentially between 1995 and 2000, then it stabilizes at about 3.5% per year. The number of GP consultations by men with ED increases up to 1999, after which it stabilizes at about 1.8% per year. CONCLUSION: We suggest that the availability and awareness of a new pharmacological option induced a change of behavior among GPs and their patients.

Risk factors for deterioration of erectile function: the Krimpen study.

This report from the Krimpen study explored the relationship between the determinants for worsening of erectile function in the open population. In Krimpen aan den IJssel (a municipality near Rotterdam), all men aged 50-75 years, without cancer of the prostate or the bladder and without a history of radical prostatectomy or neurogenic bladder disease, were invited to participate in June 1995. The response rate was 50%. The follow-up was until June 2004. At baseline a visit to a health centre for the measurement of urinalysis, height, weight and blood pressure was part of the ongoing study. During baseline and at the first follow-up, second follow-up and third follow-up, a self-administered booklet consisting of a compilation of validated questionnaires including the International Continence Society male sex questionnaire was completed. At the urology outpatient clinic, a urological workup was measured. All participants were asked to keep a frequency-volume chart for 3 days. A multivariate Cox-proportional hazard model was constructed to find the determinants of worsening of erectile function, correcting for age. Total follow-up time was 4948 person years consisting of 975 men. During follow-up, 441 events of worsening of erectile function occurred. Multivariate Cox-proportional hazard ratio analyses showed that body mass index (BMI), irritative lower urinary tract symptoms, diabetes mellitus, chronic obstructive pulmonary disease (COPD) and sexual inactivity were determinants with significant hazard ratios. In addition to age, determinants for a deterioration of erectile function based on multivariate longitudinal analyses are BMI, diabetes mellitus, COPD, sexual inactivity and irritative IPSS. The mechanism of various determinants is discussed.

Loss to follow-up in a longitudinal study on urogenital tract symptoms in Dutch older men.

OBJECTIVE: To describe loss to follow-up (LTFU) in a longitudinal community-based study on urogenital tract dysfunction in older men. PATIENTS AND METHODS: A cohort study of men recruited from a Dutch municipality was performed. A baseline study and two follow-up rounds--all with questionnaires and additional measurements--were performed with, on average, 2.1-year intervals. Baseline characteristics were compared between participants and non-participants in the first and in the second follow-up study. RESULTS: The response rates in the first and in the second follow-up were 78.0 and 80.0%, respectively. Various characteristics were found to be related to LTFU (i.e., more than 5% difference in response rate). Lower urinary tract symptoms were related to LTFU in the first and second follow-up. Sexual dysfunction was related to LTFU only in the second follow-up. Adjustment for confounders yielded odds ratios for the primary outcome variables (lower urinary tract symptoms, sexual dysfunction, and health status) that approximated the value of 1. LTFU according to these variables was different in men with and without other chronic illnesses. CONCLUSIONS: LTFU seems not to be related to the primary outcome variables in this study. Describing response patterns in longitudinal studies is important, especially in studies involving older participants, as often is the case in urological research.