Effect of aging on endogenous level of 5 alpha-dihydrotestosterone, testosterone, estradiol, and estrone in epithelium and stroma of normal and hyperplastic human prostate.

associated with aging. Thus, the question arises whether or not a correlation exists between the well known prostatic androgen and estrogen accumulation and aging. To address this question, we measured 5a-dihydrotestosterone (DHT), testosterone, estradiol, and estrone in epithelium and stroma of six normal (NPR) and 19 BPH and correlated the values with the age of the donors (26-87 yr). The mean DHT level in NPR epithelium was significantly higher than in NPR stroma, and also significantly higher than in epithelium and stroma of BPH. The epithelial DHT level of NPR and BPH decreased with age, the correlation being statistically significant. The stromal DHT level of NPR and BPH showed no correlation with age. Concerning testosterone, generally rather low values were found which showed no correlation with age. The mean levels of estradiol and estrone were significantly higher in BPH stroma as compared to BPH epithelium as well as to NPR epithelium and stroma. In NPR, the mean levels of estradiol and estrone were significantly higher in epithelium than stroma. In NPR and BPH, the stromal estradiol and estrone levels increased significantly with age. In epithelium such a correlation between the estrogen levels and age was not found. Our results indicate that the prostatic accumulation of DHT, estradiol, and estrone is in part intimately correlated with aging, leading with increasing age to a dramatic increase of the estrogen/androgen ratio particularly in stroma of BPH

Morphologie des Stressharnkontinenz-Kontrollsystems und seine pathomorphologischen Veränderungen bei Stressharninkontinenz

Die Stressharnkontinenz wird durch die morphofunktionelle Einheit von Urethra, M. levator ani und der Fascia endopelvina gewährleistet, der Begriff "Stressharnkontinenz-Kontrollsystem" verkörpert diese Komplexität. In der vorliegenden Arbeit wurde die Morphologie des Stressharnkontinenz-Kontrollsystems kontinenter Nulliparae kernspintomographisch untersucht, um den Normalbefund zu definieren. Auf Grundlage dieser Untersuchungsergebnisse wurden Frauen mit Stressharninkontinenz (HI) kernspintomographisch untersucht, um eine Nomenklatur der MRT-Pathomorphologie des Stressharnkontinenz-Kontrollsystems bei Stressharninkontinenz vorzuschlagen. Bei den kontinenten Nulliparae (n = 20) zeigte die MRT-Morphometrie von Urethra, M. levator ani und Fascia endopelvina erhebliche anatomische Normvarianten (z.B. Urethraquerschnittsfläche von 1,7 ( 0,4 cm², Ratio 2,4; Volumen des M. levator ani 33,1 ( 8,1 cm³, Ratio 2,5), die in der "Ratio" (Vielfaches des größten zum kleinsten Messwert) zum Ausdruck kommen, eine Definition des "Normalwertes" noch nicht zulassen und ein konstitutionelles Risiko für die Entstehung einer Funktionsstörung des Stressharnkontinenz-Kontrollsystems vermuten lassen. Aufgrund der morphometrischen Normvarianten des Stressharnkontinenz-Kontrollsystems kontinenter Nulliparae wurden bei den Frauen mit HI (n = 54) die MRT-Befunde von Urethra, M. levator ani und Fascia endopelvina nach qualitativen Kriterien bewertet. Eine in der PD-gewichteten Aufnahme erhöhte Signalintensität der quergestreiften Muskulatur wurde pathologisch gewertet und ist durch biochemische bzw. morphologische Veränderungen der Muskulatur (Atrophie, vermehrte Fett-, Wasser- oder Laktateinlagerung) bedingt. Der Vergleich beider Studienkollektive zeigte diese HI-typische Veränderung am M. sphincter urethrae externus und M. levator ani (0 % bei Nulliparae vs. 50 % bzw. 28 % bei Frauen mit HI). Ein dorsaler Substanzverlust des M. sphincter urethrae externus (0 % bei Nulliparae vs. 37 % bei Frauen mit HI) und ein einseitiger Substanzverlust des M. levator ani (0 % bei Nulliparae vs. 30 % bei Frauen mit HI) können ebenfalls als HI-typisch gewertet werden. Der Verlust der symphysenwärts konkaven Konfiguration der vorderen Vaginalwand ist durch einen lateralen Fasziendefekt bedingt und HI-typisch (0 % bei Nulliparae vs. 39 % bei Frauen mit HI). Zentrale Fasziendefekte haben ebenfalls einen Einfluss auf die Pathogenese der HI (0 % bei Nulliparae vs. 39 % bei Frauen mit HI). MRT-Untersuchungen des Stressharnkontinenz-Kontrollsystems tragen zum Verständnis der Anatomie und ihrer Normvarianten bei und können Befunde objektivieren, die den aktuellen Theorien zur Pathogenese der HI gerecht werden. Die MRT hat damit einen hohen Stellenwert in der urogynäkologischen Forschung.The preservation of urinary continence during stress is ensured by the morphofunctional unit of the urethra, the levator ani muscle, and the endopelvic fascia, whose complex interaction is reflected by the cover term "stress urinary continence control system". The present study investigated the morphology of the stress urinary continence control system in continent nulliparous women by magnetic resonance imaging (MRI) to define its normal anatomy. Based on these results, MRI was performed in women with stress urinary incontinence (UI) to develop a consistent terminology for the pathomorphologic changes of the stress urinary continence control system in stress UI visualized by MRI. In the continent nulliparous women (n = 20) MRI morphometry of the urethra, levator ani muscle, and endopelvic fascia revealed considerable variation in normal anatomy (e.g., cross-sectional area of urethra: 1.7 ( 0.4 cm², ratio 2.4; volume of levator ani muscle: 33.1 ( 8.1 cm³, ratio 2.5) as reflected by the calculated ratios (relation between the maximum and minimum values). These results preclude the definition of normal values and suggest that there is a constitutional risk for the development of dysfunction of the stress urinary continence control system. Because of the morphometric variation found in the normal stress urinary continence control system in continent nulliparious women, the MR images of the urethra, levator ani muscle, and endopelvic fascia acquired in women with UI (n = 54) were analyzed according to qualitative criteria. An increased signal intensity of striated muscle on proton-density-weighted images was classified as abnormal. This increase is caused by biochemical or morphologic changes of the muscle (atrophy, increased deposition of fat, water, or lactate). Comparison of both study groups demonstrated this typical UI-associated change in the external urethral sphincter muscle and the levator ani muscle (0 % in nulliparous women vs. 50 % and 28 %, respectively, in women with UI). A dorsal loss of muscle mass of the external urethral sphincter (0 % in nulliparous women vs. 37 % in UI) and a unilateral loss of mass of the levator ani muslce (0 % in nulliparous women vs. 30 % in women with UI) can likewise be regarded as typical features of UI. Another typical finding in UI is the loss of the hammock configuration of the anterior vaginal wall that is caused by a lateral fascial defect (0 % in nulliparous women vs. 39 % in UI). Defects of the central fascia are likewise involved in the pathogenesis of UI (0 % in nulliparous women vs. 39 % in UI). MRI studies of the stress urinary continence control system help us to gain new insights into its anatomy and normal morphologic variation and yield objective results to corroborate current theories on the pathogenesis of UI. Hence MRI has an important role in urogynecologic research

Patient Reported Outcomes Tools in an Observational Study of Female Stress Urinary Incontinence

Aims: To determine which patient characteristics, incontinence and non-incontinence related, are associated with the symptom severity scores of the Urogenital Distress Inventory (UDI) and the International Consultation on Incontinence Questionnaire Urinary Incontinence (ICIQ-UI); and to determine the association of both patient characteristics and symptom severity scores with quality-of-life scores of the Incontinence Impact Questionnaire (IIQ) and the Incontinence-Quality of Life (I-QOL) questionnaire. Methods: Women presenting with stress urinary incontinence (SUI) symptoms in primary and secondary care entered the Stress Urinary Incontinence Treatment Study (SUIT), an observational study evaluating the cost-effectiveness of duloxetine compared to other non-surgical treatments for SUI. At enrolment patients completed the UDI-6, the short form ICIQ-UI, the IIQ-7 and the I-QOL. Multivariate linear regressions were performed with the UDI-6, ICIQ-UI SF, IIQ-7, and I-QOL as outcomes. Results: The total number of incontinence episodes is the most significant explanatory variable of the two symptom questionnaire scores, but the UDI-6 score also reflects the type of incontinence. The variability of the condition-specific quality-of-life questionnaires is primarily explained by the symptom severity questionnaire scores. Although there is a high intercorrelation, both these symptom questionnaires independently contributed significantly to the IIQ-7 and I-QOL total scores. Conclusions: The UDI-6 and ICIQ-UI SF can be regarded as scientifically sound symptom questionnaires in UI evaluation; but they have differences. Since the UDI-6 and ICIQ-UI SF independently contribute to the quality-of-life scores, this suggests that in incontinence research symptom questionnaires should not focus only on incontinence, but on a broader range of urogenital symptoms. Neurourol. Urodynam. 29:348-353, 2010. (C) 2009 Wiley-Liss, Inc

Patient Characteristics Impacting Health State Index Scores, Measured by the EQ-5D of Females with Stress Urinary Incontinence Symptoms

AbstractObjectiveTo describe the characteristics of women seeking treatment for symptoms of stress urinary incontinence (SUI) and to investigate the association of SUI symptoms with generic health-related quality of life (HRQoL) as measured by the EuroQol (EQ-5D) instrument.MethodsThe Stress Urinary Incontinence Treatment (SUIT) study was a 12-month observational study in four European countries that evaluated the cost-effectiveness of duloxetine compared with other forms of nonsurgical intervention in the treatment of the symptoms of SUI. Four hundred thirty-one physicians observed women seeking treatment for their SUI, and recorded the care provided and the outcomes of that care at enrollment and at 3, 6 and 12 months afterward The impact of SUI on baseline HRQoL as expressed by the EQ-5D index score was assessed by linear and logistic regression.ResultsThree thousand seven hundred sixty-two women were enrolled into SUIT, with the largest patient group from Germany. Overall, the majority of women were postmenopausal, had a mean age of 58.0 years, were not current smokers, and tended to be overweight (mean body mass index [BMI] = 27.7 kg/m2), with at least one comorbidity. The health state index scores were significantly and independently influenced by the presence of comorbidity(ies) affecting quality of life, total number of stress and urge incontinence episodes, urinary incontinence subtype, comorbidity(ies) affecting incontinence, BMI, socioeconomic status, educational status, age, and country.ConclusionThis article describes the characteristics of patients at the SUIT enrollment visit, and demonstrates that the number of incontinence episodes has a significant impact on the EQ-5D index score