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BackgroundWomen are more likely to present with genitourinary complaints immediately after exposure to interpersonal violence, but little is known about the long-term effects of violence on women's urologic health, including their susceptibility to bladder pain and infections.ObjectiveTo determine whether lifetime interpersonal violence exposure and current posttraumatic stress disorder (PTSD) symptoms are associated with the prevalence or severity of painful bladder symptoms and a greater lifetime history of antibiotic-treated urinary tract infections in community-dwelling midlife and older women.Study designWe examined the cross-sectional data from a multiethnic cohort of community-dwelling women aged 40 to 80 years enrolled in a northern California integrated healthcare system. Women completed structured self-report questionnaires about their past exposure to physical and verbal/emotional intimate partner violence and sexual assault. The symptoms of PTSD were assessed using the PTSD checklist for the Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition, Civilian version. Additional structured self-report measures assessed the current bladder pain, other lower urinary tract symptoms, and the history of antibiotic-treated urinary tract infections. Multivariable logistic regression models examined self-reported interpersonal violence exposure history and current PTSD symptoms in relation to current bladder pain and antibiotic-treated urinary tract infection history.ResultsAmong 1974 women (39% non-Latina White, 21% Black, 20% Latina, and 19% Asian), 22% reported lifetime interpersonal violence exposure, 22% reported bladder pain, and 60% reported a history of ever having an antibiotic-treated urinary tract infection. Lifetime experiences of sexual assault (odds ratio, 1.39; [95% confidence interval, 1.02-1.88]) and current PTSD symptoms (odds ratio, 1.96; [95% confidence interval, 1.45-2.65]) were associated with current bladder pain. A lifetime experience of physical intimate partner violence was associated with having a urinary tract infection at any time in life previously (odds ratio, 1.38; [95% confidence interval, 1.00-1.86]), as was emotional intimate partner violence (odds ratio, 1.88; [95% confidence interval, 1.43-2.48]), sexual assault (odds ratio, 1.44; [95% confidence interval, 1.09-1.91]), and current PTSD symptoms (odds ratio, 1.54; [95% confidence interval, 1.16-2.03]).ConclusionIn this ethnically diverse, community-based cohort, lifetime interpersonal violence exposures and current PTSD symptoms were independently associated with current bladder pain and the lifetime history of antibiotic-treated urinary tract infections in midlife to older women. The findings suggest that interpersonal violence and PTSD symptoms may be underrecognized markers of risk for urologic pain and infections in women, highlighting a need for trauma-informed care of these issues.

Even distinct cancer types share biological hallmarks. Here, we investigate polygenic risk score (PRS)-specific pleiotropy across 16 cancers in European ancestry individuals from the Genetic Epidemiology Research on Adult Health and Aging cohort (16,012 cases, 50,552 controls) and UK Biobank (48,969 cases, 359,802 controls). Within cohorts, each PRS is evaluated in multivariable logistic regression models against all other cancer types. Results are then meta-analyzed across cohorts. Ten positive and one inverse cross-cancer associations are found after multiple testing correction. Two pairs show bidirectional associations; the melanoma PRS is positively associated with oral cavity/pharyngeal cancer and vice versa, whereas the lung cancer PRS is positively associated with oral cavity/pharyngeal cancer, and the oral cavity/pharyngeal cancer PRS is inversely associated with lung cancer. Overall, we validate known, and uncover previously unreported, patterns of pleiotropy that have the potential to inform investigations of risk prediction, shared etiology, and precision cancer prevention strategies.

Deciphering the shared genetic basis of distinct cancers has the potential to elucidate carcinogenic mechanisms and inform broadly applicable risk assessment efforts. Here, we undertake genome-wide association studies (GWAS) and comprehensive evaluations of heritability and pleiotropy across 18 cancer types in two large, population-based cohorts: the UK Biobank (408,786 European ancestry individuals; 48,961 cancer cases) and the Kaiser Permanente Genetic Epidemiology Research on Adult Health and Aging cohorts (66,526 European ancestry individuals; 16,001 cancer cases). The GWAS detect 21 genome-wide significant associations independent of previously reported results. Investigations of pleiotropy identify 12 cancer pairs exhibiting either positive or negative genetic correlations; 25 pleiotropic loci; and 100 independent pleiotropic variants, many of which are regulatory elements and/or influence cross-tissue gene expression. Our findings demonstrate widespread pleiotropy and offer further insight into the complex genetic architecture of cross-cancer susceptibility.

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Insulin-like growth factors (IGFs) and insulin-like growth factor binding proteins (IGFBPs) have been implicated in the aetiology of several cancers. To better understand whether anthropometric, behavioural and sociodemographic factors may play a role in cancer risk via IGF signalling, we examined the cross-sectional associations of these exposures with circulating concentrations of IGFs (IGF-I and IGF-II) and IGFBPs (IGFBP-1, IGFBP-2 and IGFBP-3). The Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group dataset includes individual participant data from 16,024 male controls (i.e. without prostate cancer) aged 22-89 years from 22 prospective studies. Geometric means of protein concentrations were estimated using analysis of variance, adjusted for relevant covariates. Older age was associated with higher concentrations of IGFBP-1 and IGFBP-2 and lower concentrations of IGF-I, IGF-II and IGFBP-3. Higher body mass index was associated with lower concentrations of IGFBP-1 and IGFBP-2. Taller height was associated with higher concentrations of IGF-I and IGFBP-3 and lower concentrations of IGFBP-1. Smokers had higher concentrations of IGFBP-1 and IGFBP-2 and lower concentrations of IGFBP-3 than nonsmokers. Higher alcohol consumption was associated with higher concentrations of IGF-II and lower concentrations of IGF-I and IGFBP-2. African Americans had lower concentrations of IGF-II, IGFBP-1, IGFBP-2 and IGFBP-3 and Hispanics had lower IGF-I, IGF-II and IGFBP-3 than non-Hispanic whites. These findings indicate that a range of anthropometric, behavioural and sociodemographic factors are associated with circulating concentrations of IGFs and IGFBPs in men, which will lead to a greater understanding of the mechanisms through which these factors influence cancer risk.

Erectile dysfunction affects millions of men worldwide. Twin studies support the role of genetic risk factors underlying erectile dysfunction, but no specific genetic variants have been identified. We conducted a large-scale genome-wide association study of erectile dysfunction in 36,649 men in the multiethnic Kaiser Permanente Northern California Genetic Epidemiology Research in Adult Health and Aging cohort. We also undertook replication analyses in 222,358 men from the UK Biobank. In the discovery cohort, we identified a single locus (rs17185536-T) on chromosome 6 near the single-minded family basic helix-loop-helix transcription factor 1 (SIM1) gene that was significantly associated with the risk of erectile dysfunction (odds ratio = 1.26, P = 3.4 × 10-25). The association replicated in the UK Biobank sample (odds ratio = 1.25, P = 6.8 × 10-14), and the effect is independent of known erectile dysfunction risk factors, including body mass index (BMI). The risk locus resides on the same topologically associating domain as SIM1 and interacts with the SIM1 promoter, and the rs17185536-T risk allele showed differential enhancer activity. SIM1 is part of the leptin-melanocortin system, which has an established role in body weight homeostasis and sexual function. Because the variants associated with erectile dysfunction are not associated with differences in BMI, our findings suggest a mechanism that is specific to sexual function.

BACKGROUND:Some studies have linked long-term exposure to traffic related air pollutants (TRAP) with adverse cardiovascular health outcomes; however, previous studies have not linked highly variable concentrations of TRAP measured at street-level within neighborhoods to cardiovascular health outcomes. METHODS:Long-term pollutant concentrations for nitrogen dioxide [NO2], nitric oxide [NO], and black carbon [BC] were obtained by street-level mobile monitoring on 30 m road segments and linked to residential addresses of 41,869 adults living in Oakland during 2010 to 2015. We fit Cox proportional hazard models to estimate the relationship between air pollution exposures and time to first cardiovascular event. Secondary analyses examined effect modification by diabetes and age. RESULTS:Long-term pollutant concentrations [mean, (standard deviation; SD)] for NO2, NO and BC were 9.9 ppb (SD 3.8), 4.9 ppb (SD 3.8), and 0.36 μg/m3 (0.17) respectively. A one SD increase in NO2, NO and BC, was associated with a change in risk of a cardiovascular event of 3% (95% confidence interval [CI] -6% to 12%), 3% (95% CI -5% to 12%), and - 1% (95% CI -8% to 7%), respectively. Among the elderly (≥65 yrs), we found an increased risk of a cardiovascular event of 12% for NO2 (95% CI: 2%, 24%), 12% for NO (95% CI: 3%, 22%), and 7% for BC (95% CI: -3%, 17%) per one SD increase. We found no effect modification by diabetes. CONCLUSIONS:Street-level differences in long-term exposure to TRAP were associated with higher risk of cardiovascular events among the elderly, indicating that within-neighborhood differences in TRAP are important to cardiovascular health. Associations among the general population were consistent with results found in previous studies, though not statistically significant.

Prostate-specific antigen (PSA) levels have been used for detection and surveillance of prostate cancer (PCa). However, factors other than PCa-such as genetics-can impact PSA. Here we present findings from a genome-wide association study (GWAS) of PSA in 28,503 Kaiser Permanente whites and 17,428 men from replication cohorts. We detect 40 genome-wide significant (P

ObjectiveThis study aims to identify factors associated with greater impact of vaginal symptoms on the functioning and well-being of postmenopausal women.MethodsPostmenopausal women who reported vaginal dryness, itching, irritation, or pain with sexual activity completed the multidimensional Day-to-day Impact of Vaginal Aging (DIVA) questionnaire and underwent assessment of multiple sociodemographic and clinical factors that have the potential to influence the impact of vaginal symptoms. Multivariable linear regression analyses examined relationships between selected participant characteristics and DIVA scale scores assessing symptom impact on activities of daily living, emotional well-being, self-concept and body image, and sexual functioning.ResultsAmong 745 symptomatic participants, the mean (SD) age was 56 (9) years, and 66% were racial/ethnic minorities. Women with comorbid depression reported greater impact of vaginal symptoms on all dimensions of functioning and well-being measured by the DIVA questionnaire (11%-22% estimated increase in impact scores associated with every three-point increase in Hospital and Anxiety Depression Scale scores). Women with urinary incontinence also reported greater impact of vaginal symptoms on activities of daily living, emotional well-being, and self-concept and body image (27%-37% estimated increase in impact scores). Age, partner status, frequency of sexual activity, general health, and body mass index also predicted greater impact on at least one domain.ConclusionsFindings suggest that special efforts should be made to identify and treat vaginal symptoms in postmenopausal women known to have depression or urinary incontinence, as these women may experience greater impact of vaginal symptoms on multiple domains of functioning and quality of life.

UnlabelledA genome-wide association study (GWAS) of prostate cancer in Kaiser Permanente health plan members (7,783 cases, 38,595 controls; 80.3% non-Hispanic white, 4.9% African-American, 7.0% East Asian, and 7.8% Latino) revealed a new independent risk indel rs4646284 at the previously identified locus 6q25.3 that replicated in PEGASUS (N = 7,539) and the Multiethnic Cohort (N = 4,679) with an overall P = 1.0 × 10(-19) (OR, 1.18). Across the 6q25.3 locus, rs4646284 exhibited the strongest association with expression of SLC22A1 (P = 1.3 × 10(-23)) and SLC22A3 (P = 3.2 × 10(-52)). At the known 19q13.33 locus, rs2659124 (P = 1.3 × 10(-13); OR, 1.18) nominally replicated in PEGASUS. A risk score of 105 known risk SNPs was strongly associated with prostate cancer (P < 1.0 × 10(-8)). Comparing the highest to lowest risk score deciles, the OR was 6.22 for non-Hispanic whites, 5.82 for Latinos, 3.77 for African-Americans, and 3.38 for East Asians. In non-Hispanic whites, the 105 risk SNPs explained approximately 7.6% of disease heritability. The entire GWAS array explained approximately 33.4% of heritability, with a 4.3-fold enrichment within DNaseI hypersensitivity sites (P = 0.004).SignificanceTaken together, our findings of independent risk variants, ethnic variation in existing SNP replication, and remaining unexplained heritability have important implications for further clarifying the genetic risk of prostate cancer. Our findings also suggest that there may be much promise in evaluating understudied variation, such as indels and ethnically diverse populations.

IntroductionRecent cross-sectional studies suggest that restless legs syndrome (RLS) may be associated with an increased prevalence of cardiovascular disease (CVD) comorbidity or risk factors. We evaluated whether primary or secondary RLS was associated with an increased risk of incident cardiovascular disease in a retrospective cohort study within Kaiser Permanente Northern California (KPNC).MethodsWe identified members of KPNC with primary RLS and secondary RLS between 1999 and 2008 by an algorithm that incorporated longitudinal clinical records related to the diagnosis and treatment of RLS and comorbidities. We then matched each RLS case with up to 50 individuals with no clinical records of RLS by age, sex, race/ethnicity, zip code, and membership duration. For the analyses we excluded any individual with coronary artery disease (CAD: angina, acute myocardial infarction, coronary revascularization procedure, CAD death), CVD (CAD plus stroke), and hypertension at baseline. New cardiovascular events were determined from clinical records. Follow-up ended at an outcome event, disenrollment from KPNC, or death, whichever occurred earliest. There were over 473,358 person-y of follow-up in this cohort analysis with a mean follow-up time of 3.91 y and range from 6 mo to 12 y. Survival analysis techniques, including survival curves and proportional hazard regression models, were used to assess the association between RLS status and CVD.ResultsThere were 7,621 primary RLS and 4,507 secondary RLS cases identified and included in the study. In general, primary RLS cases were younger and had less comorbidity than secondary RLS cases. During the follow-up period, CVD was diagnosed in 478 primary RLS cohort members, CAD was diagnosed in 310, and hypertension events were identified in 1,466. Diagnosis in secondary RLS cohort members was made during the follow-up period with 451, 338, and 598 CVD, CAD, and hypertension events, respectively. Subjects with primary RLS had a similar risk of incident CVD (hazard ratio (HR) = 0.95; 95% confidence interval (CI) = 0.86-1.04) and CAD (HR = 0.99; 95% CI = 0.89-1.13) to the comparison cohort, with a slight elevation in the risk of hypertension events (HR = 1.19; 95% CI = 1.12-1.25), after multivariable adjustment. Individuals classified as secondary RLS had a significant increased risk of CVD (HR = 1.33; 95% CI = 1.21-1.46), CAD (HR = 1.40; 95% CI = 1.25-1.56), and hypertension (HR = 1.28; 95% CI = 1.18-1.40).ConclusionPrimary restless legs syndrome (RLS) was not associated with new-onset cardiovascular disease (CVD) or coronary artery disease (CAD) but was associated with a slight increased risk of hypertension. In contrast, secondary RLS was associated with an increased risk of CVD, CAD, and hypertension.

ObjectiveTo examine the prevalence, predictors, and effects of nocturia in women and evaluate overlaps with established urinary tract disorders.MethodsThis was a cross-sectional analysis of 2,016 women, aged 40 years and older, recruited from Kaiser Permanente Northern California from 2008 to 2012. Nocturia and other urinary symptoms were assessed using structured interviewer-administered questionnaires. Nocturia was defined as patient-reported nocturnal voiding of two or more times per night over a typical week.ResultsThirty-four percent (n=692) reported nocturia, and 40% of women with nocturia reported no other urinary tract symptom. Women with nocturia were older (mean age 58 compared with 55 years) (odds ratio [OR] per 5-year increase 1.21, 95% confidence interval [CI] 1.12-1.31), more likely black (45%) (OR 1.75, 95% CI 1.30-2.35) or Latina (37%) (OR 1.36, 95% CI 1.02-1.83) compared with non-Latina white (30%), have worse depression (mean Hospital Anxiety and Depression Scale score 3.8 compared with 2.8) (OR per 1-point increase in Hospital Anxiety and Depression Scale score 1.08, 95% CI 1.04-1.12), and worse mobility (mean Timed Up-and-Go 11.3 compared with 10 seconds) (OR per 5-second increase in Timed Up-and-Go 1.29, 95% CI 1.05-1.58). Nocturia occurred more among women with hysterectomy (53% compared with 33%) (OR 1.78, 95% CI 1.08-2.94), hot flushes (38% compared with 32%) (OR 1.49, 95% CI 1.19-1.87), and vaginal estrogen use (42% compared with 34%) (OR 1.50, 95% CI 1.04-2.18).ConclusionNocturia is common in women and not necessarily attributable to other urinary tract disorders. Factors not linked to bladder function may contribute to nocturia risk, underlining the need for multiorgan prevention and treatment strategies.Level of evidenceII.

IntroductionLittle is known about sexual activity and function in women with multiple chronic health conditions.AimTo examine the impact of multimorbidity on sexual activity and function in middle-aged and older women.MethodsMultiethnic cross-sectional cohort of 1,997 community-dwelling women (mean age of 60.2 [±9.5] years) in California. Structured questionnaires assessed prior diagnoses of common cardiometabolic, colorectal, neuropsychiatric, respiratory, musculoskeletal, and genitourinary conditions.Main outcome measuresSexual desire, frequency of sexual activity, overall sexual satisfaction, and specific sexual problems (i.e., difficulty with arousal, lubrication, orgasm, and pain) were assessed by structured questionnaires.ResultsSeventy-one percent of women had two or more diagnosed chronic conditions. Fifty-nine percent reported low sexual desire, 53% reported less than monthly sexual activity, and 47% reported low overall sexual satisfaction. Multimorbidity was associated with increased odds of reporting low sexual desire (OR = 1.11, 95% CI = 1.06-1.17, per each additional chronic condition), less than monthly sexual activity (OR = 1.11, 95% CI = 1.05-1.17 per each additional condition), and low sexual satisfaction (OR = 1.10, 95% CI = 1.04-1.16 per each additional condition), adjusting for age, race/ethnicity, and partner status. Depression and urinary incontinence were each independently associated with low desire (OR = 1.53, 95% CI = 1.19-1.97, and OR = 1.23, 95% CI = 1.00-1.52, respectively), less than monthly sexual activity (OR = 1.39, 95% CI = 1.06-1.83, and OR = 1.29, 95% CI = 1.02-1.62, respectively), and low sexual satisfaction (OR = 1.49, 95% CI = 1.14-1.93, and OR = 1.38, 95% CI = 1.11-1.73, respectively), adjusting for other types of conditions. After adjustment for total number of chronic conditions, age remained a significant predictor of low desire and less than monthly sexual activity, but not sexual satisfaction.ConclusionsWomen with multiple chronic health conditions are at increased risk for decreased sexual function. Depression and incontinence may have particularly strong effects on sexual desire, frequency of activity, and satisfaction in women, independent of other comorbid conditions. Women's overall sexual satisfaction may be more strongly influenced by multimorbidity than age.

IntroductionLittle is known about sexual activity and function in women with multiple chronic health conditions.AimTo examine the impact of multimorbidity on sexual activity and function in middle-aged and older women.MethodsMultiethnic cross-sectional cohort of 1,997 community-dwelling women (mean age of 60.2 [±9.5] years) in California. Structured questionnaires assessed prior diagnoses of common cardiometabolic, colorectal, neuropsychiatric, respiratory, musculoskeletal, and genitourinary conditions.Main outcome measuresSexual desire, frequency of sexual activity, overall sexual satisfaction, and specific sexual problems (i.e., difficulty with arousal, lubrication, orgasm, and pain) were assessed by structured questionnaires.ResultsSeventy-one percent of women had two or more diagnosed chronic conditions. Fifty-nine percent reported low sexual desire, 53% reported less than monthly sexual activity, and 47% reported low overall sexual satisfaction. Multimorbidity was associated with increased odds of reporting low sexual desire (OR = 1.11, 95% CI = 1.06-1.17, per each additional chronic condition), less than monthly sexual activity (OR = 1.11, 95% CI = 1.05-1.17 per each additional condition), and low sexual satisfaction (OR = 1.10, 95% CI = 1.04-1.16 per each additional condition), adjusting for age, race/ethnicity, and partner status. Depression and urinary incontinence were each independently associated with low desire (OR = 1.53, 95% CI = 1.19-1.97, and OR = 1.23, 95% CI = 1.00-1.52, respectively), less than monthly sexual activity (OR = 1.39, 95% CI = 1.06-1.83, and OR = 1.29, 95% CI = 1.02-1.62, respectively), and low sexual satisfaction (OR = 1.49, 95% CI = 1.14-1.93, and OR = 1.38, 95% CI = 1.11-1.73, respectively), adjusting for other types of conditions. After adjustment for total number of chronic conditions, age remained a significant predictor of low desire and less than monthly sexual activity, but not sexual satisfaction.ConclusionsWomen with multiple chronic health conditions are at increased risk for decreased sexual function. Depression and incontinence may have particularly strong effects on sexual desire, frequency of activity, and satisfaction in women, independent of other comorbid conditions. Women's overall sexual satisfaction may be more strongly influenced by multimorbidity than age.

BackgroundAlthough many studies have shown that diabetes increases the risk for urinary incontinence, it is unclear whether poor glycemic control in women with diabetes is associated with incontinence. This study aims to determine the relationship between the hemoglobin A1c (HbA1c) level and urinary incontinence in a large, diverse cohort of older women.MethodsWe examined 6026 older women who responded to a survey (62% response rate) and were enrolled in the Diabetes and Aging Study, an ethnically stratified random sample of patients with diabetes enrolled in Kaiser Permanente Northern California. Our primary independent variable was the mean of all HbA1c measurements in the year preceding the survey. Outcomes included the presence/absence of incontinence and limitations in daily activities due to incontinence. We used modified Poisson regression and ordinal logistic regression models to account for age, race, body mass index, parity, diabetes treatment, duration of diabetes, and comorbidity.ResultsSixty-five percent of women reported incontinence (mean age 59±10 years). After adjustment, HbA1c levels were not associated with the presence or absence of incontinence. However, among women reporting incontinence, HbA1c ≥9% was associated with more limitations due to incontinence than HbA1c

ObjectiveTo examine relationships among parity, mode of delivery, and other parturition-related factors with women's sexual function later in life.MethodsSelf-administered questionnaires examined sexual desire, activity, satisfaction, and problems in a multiethnic cohort of women aged 40 years and older with at least one past childbirth event. Trained abstractors obtained information on parity, mode of delivery, and other parturition-related factors from archived records. Multivariable regression models examined associations with sexual function controlling for age, race or ethnicity, partner status, diabetes, and general health.ResultsAmong 1,094 participants, mean (standard deviation) age was 56.3 (±8.7) years, 568 (43%) were racial or ethnic minorities (214 African American, 171 Asian, and 183 Latina), and 963 (88%) were multiparous. Fifty-six percent (n=601) reported low sexual desire; 53% (n=577) reported less than monthly sexual activity, and 43% (n=399) reported low overall sexual satisfaction. Greater parity was not associated with increased risk of reporting low sexual desire (adjusted odds ratio [OR] 1.08, confidence interval [CI] 0.96-1.21 per each birth), less than monthly sexual activity (adjusted OR 1.05, CI 0.93-1.20 per each birth), or low sexual satisfaction (adjusted OR 0.96, CI 0.85-1.09 per each birth). Compared with vaginal delivery alone, women with a history of cesarean delivery were not significantly more likely to report low desire (adjusted OR 0.71, CI 0.34-1.47), less than monthly sexual activity (adjusted OR 1.03, CI 0.46-2.32), or low sexual satisfaction (adjusted OR 0.57, CI 0.26-1.22). Women with a history of operative-assisted delivery were more likely to report low desire (adjusted OR 1.38, CI 1.04-1.83).ConclusionsAmong women with at least one childbirth event, parity and mode of delivery are not major determinants of sexual desire, activity, or satisfaction later in life.Level of evidenceII.

BackgroundThe impact of anal incontinence on women's sexual function is poorly understood.ObjectiveThe aim of this study was to investigate the relationship between anal incontinence and sexual activity and functioning in women.DesignThis is a cross-sectional study.SettingsThis investigation was conducted in a community-based integrated health care delivery system.PatientsIncluded were 2269 ethnically diverse women aged 40 to 80 years.Main outcome measuresSelf-administered questionnaires assessed accidental leakage of gas (flatal incontinence) and fluid/mucus/stool (fecal incontinence) in the past 3 months. Additional questionnaires assessed sexual activity, desire and satisfaction, as well as specific sexual problems (difficulty with arousal, lubrication, orgasm, or pain). Multivariable logistic regression models compared sexual function in women with 1) isolated flatal incontinence, 2) fecal incontinence (with or without flatal incontinence), and 3) no fecal/flatal incontinence, controlling for potential confounders.ResultsTwenty-four percent of women reported fecal incontinence and 43% reported isolated flatal incontinence in the previous 3 months. The majority were sexually active (62% of women without fecal/flatal incontinence, 66% with isolated flatal incontinence, and 60% with fecal incontinence; p = 0.06). In comparison with women without fecal/flatal incontinence, women with fecal incontinence were more likely to report low sexual desire (OR: 1.41 (CI: 1.10-1.82)), low sexual satisfaction (OR: 1.56 (CI: 1.14-2.12)), and limitation of sexual activity by physical health (OR: 1.65 (CI: 1.19-2.28)) after adjustment for confounders. Among sexually active women, women with fecal incontinence were more likely than women without fecal/flatal incontinence to report difficulties with lubrication (OR: 2.66 (CI: 1.76-4.00)), pain (OR: 2.44 (CI: 1.52-3.91)), and orgasm (OR: 1.68 (CI: 1.12-2.51)). Women with isolated flatal incontinence reported sexual functioning similar to women without fecal/flatal incontinence.LimitationsThe cross-sectional design prevented evaluation of causality.ConclusionsAlthough most women with fecal incontinence are at high risk for several aspects of sexual dysfunction, the presence of fecal incontinence does not prevent women from engaging in sexual activity. This indicates that sexual function is important to women with anal incontinence and should be prioritized during therapeutic management.

ObjectiveDiabetes mellitus is an established risk factor for sexual dysfunction in men, but its effect on female sexual function is poorly understood. We examined the relationship of diabetes to sexual function in middle-aged and older women.MethodsSexual function was examined in a cross-sectional cohort of ethnically diverse women aged 40-80 years using self-administered questionnaires. Multivariable regression models compared self-reported sexual desire, frequency of sexual activity, overall sexual satisfaction, and specific sexual problems (difficulty with lubrication, arousal, orgasm, or pain) among insulin-treated diabetic, non-insulin-treated diabetic, and nondiabetic women. Additional models assessed relationships between diabetic end-organ complications (heart disease, stroke, renal dysfunction, and peripheral neuropathy) and sexual function.ResultsAmong the 2,270 participants, mean±standard deviation age was 55±9.2 years, 1,006 (44.4%) were non-Latina white, 486 (21.4%) had diabetes, and 139 (6.1%) were taking insulin. Compared with 19.3% of nondiabetic women, 34.9% of insulin-treated diabetic women (adjusted odds ratio [OR] 2.04, 95% confidence interval [CI] 1.32-3.15) and 26.0% of non-insulin-treated diabetic women (adjusted OR 1.42, 95% CI 1.03-1.94) reported low overall sexual satisfaction. Among sexually active women, insulin-treated diabetic women were more likely to report problems with lubrication (OR 2.37, 95% CI 1.35-4.16) and orgasm (OR 1.80, 95% CI 1.01-3.20) than nondiabetic women. Among all diabetic women, end-organ complications such as heart disease, stroke, renal dysfunction, and peripheral neuropathy were associated with decreased sexual function in at least one domain.ConclusionCompared with nondiabetic women, diabetic women are more likely to report low overall sexual satisfaction. Insulin-treated diabetic women also appear at higher risk for problems such as difficulty with lubrication and orgasm. Prevention of end-organ complications may be important in preserving sexual activity and function in diabetic women.Level of evidenceII.

ObjectiveTo investigate the relationship of lower urinary tract symptoms (LUTS) to urinary tract infection, prostatitis, sexually transmitted infection, lifetime sexual partner count, and recreational drug use in a population of men who have sex with men. LUTS in men are a source of considerable morbidity, distress, and medical expense.MethodsWe conducted a cross-sectional, Internet-based survey of urinary quality-of-life outcomes in men who have sex with men. The main outcome was the International Prostate Symptom Score (IPSS), classified as none/mild (IPSS 0-7), moderate/severe (IPSS 8-35), or severe (IPSS 20-35). The participants were also asked whether they ever sought medical attention for urinary problems.ResultsThe survey web site was accessed by 2783 men, of whom 2348 (84.3%) completed the questionnaire. The median age was 39 years (range 18-81). Age, depression, human immunodeficiency virus infection, gonorrhea, syphilis, prostatitis, and prescription drug abuse were all associated with LUTS. Men who sought medical attention for LUTS were more likely to report older age, diabetes, depression, gonorrhea, urinary tract infection history, and prostatitis.ConclusionSpecific infectious conditions of the urinary tract and depressive symptoms are independent predictors of LUTS in men who have sex with men. Although LUTS are often multifactorial, a common unifying explanation for our finding could be the effects of local and systemic inflammation on the lower urinary tract.

Following reports of an increased incidence of amyotrophic lateral sclerosis (ALS) in U.S. veterans, we have conducted a high-density genome-wide association study (GWAS) of ALS outcome and survival time in a sample of U.S. veterans. We tested ∼1.3 million single nucleotide polymorphisms (SNPs) for association with ALS outcome in 442 incident Caucasian veteran cases diagnosed with definite or probable ALS and 348 Caucasian veteran controls. To increase power, we also included genotypes from 5909 publicly-available non-veteran controls in the analysis. In the survival analysis, we tested for association between SNPs and post-diagnosis survival time in 639 Caucasian veteran cases with definite or probable ALS. After this discovery phase, we performed follow-up genotyping of 299 SNPs in an independent replication sample of Caucasian veterans and non-veterans (ALS outcome: 183 cases and 961 controls; survival: 118 cases). Although no SNPs reached genome-wide significance in the discovery phase for either phenotype, three SNPs were statistically significant in the replication analysis of ALS outcome: rs6080539 (177 kb from PCSK2), rs7000234 (4 kb from ZNF704), and rs3113494 (13 kb from LOC100506746). Two SNPs located in genes that were implicated by previous GWA studies of ALS were marginally significant in the pooled analysis of discovery and replication samples: rs17174381 in DPP6 (p = 4.4×10(-4)) and rs6985069 near ELP3 (p = 4.8×10(-4)). Our results underscore the difficulty of identifying and convincingly replicating genetic associations with a rare and genetically heterogeneous disorder such as ALS, and suggest that common SNPs are unlikely to account for a substantial proportion of patients affected by this devastating disorder.