Princeton IV consensus guidelines: PDE5 inhibitors and cardiac health.

BACKGROUND: In 1999, 1 year after the approval of the first oral phosphodiesterase type 5 (PDE5) inhibitor for the treatment of erectile dysfunction (ED), the first Princeton Consensus Conference was held to address the clinical management of men with ED who also had cardiovascular disease. These issues were readdressed in the second and third conferences. In the 13 years since the last Princeton Consensus Conference, the experience with PDE5 inhibitors is more robust, and recent new data have emerged regarding not only safety and drug-drug interactions, but also a potential cardioprotective effect of these drugs. AIM: In March 2023, an interdisciplinary group of scientists and practitioners met for the fourth Princeton Consensus Guidelines at the Huntington Medical Research Institutes in Pasadena, California, to readdress the cardiovascular workup of men presenting with ED as well as the approach to treatment of ED in men with known cardiovascular disease. METHOD: A series of lectures from experts in the field followed by Delphi-type discussions were developed to reach consensus. OUTCOMES: Consensus was reached regarding a number of issues related to erectile dysfunction and the interaction with cardiovascular health and phosphodiesterase-5 inhibitors. RESULTS: An algorithm based on recent recommendations of the American College of Cardiology and American Heart Association, including the use of computed tomography coronary artery calcium scoring, was integrated into the evaluation of men presenting with ED. Additionally, the issue of nitrate use was further considered in an algorithm regarding the treatment of ED patients with coronary artery disease. Other topics included the psychological effect of ED and the benefits of treating it; the mechanism of action of the PDE5 inhibitors; drug-drug interactions; optimizing use of a PDE5 inhibitors; rare adverse events; potential cardiovascular benefits observed in recent retrospective studies; adulteration of dietary supplements with PDE5 inhibitors; the pros and cons of over-the-counter PDE5 inhibitors; non-PDE5 inhibitor therapy for ED including restorative therapies such as stem cells, platelet-rich plasma, and shock therapy; other non-PDE5 inhibitor therapies, including injection therapy and penile prostheses; the issue of safety and effectiveness of PDE5 inhibitors in women; and recommendations for future studies in the field of sexual dysfunction and PDE5 inhibitor use were discussed. CLINICAL IMPLICATIONS: Algorithms and tables were developed to help guide the clinician in dealing with the interaction of ED and cardiovascular risk and disease. STRENGTHS AND LIMITATIONS: Strengths include the expertise of the participants and consensus recommendations. Limitations included that participants were from the United States only for this particular meeting. CONCLUSION: The issue of the intersection between cardiovascular health and sexual health remains an important topic with new studies suggesting the cardiovascular safety of PDE5 inhibitors.

Effect of phosphodiesterase type 5 inhibitors on major adverse cardiovascular events and overall mortality in a large nationwide cohort of men with erectile dysfunction and cardiovascular risk factors: A retrospective, observational study based on healthcare claims and national death index data.

BACKGROUND: Treatment with phosphodiesterase type 5 inhibitors (PDE-5is) is effective in treating erectile dysfunction (ED). AIM: The objective of this study was to determine the effect of PDE-5is on the incidence of major adverse cardiovascular (CV) events (MACE; composite outcome of CV death, hospitalization for myocardial infarction, coronary revascularization, stroke, heart failure, and unstable angina pectoris) and overall mortality. METHODS: A retrospective observational cohort study was conducted in a large US claims database in men with ≥1 diagnosis of ED without prior MACE within 1 year, from January 1, 2006, to October 31, 2020. The exposed group had ≥1 claim for PDE-5i and the unexposed group had no claims for PDE-5i, and the groups were matched up to 1:4 on baseline risk variables. OUTCOME: The primary outcome was MACE and the secondary outcomes were overall mortality and individual components of MACE, determined by multivariable Cox proportional hazard modeling. RESULTS: Matched plus multivariable analyses showed that MACE was lower by 13% in men exposed (n = 23 816) to PDE-5is (hazard ratio [HR] 0.87; 95% CI 0.79-0.95; P = .001) vs nonexposure (n = 48 682) over mean follow-up periods of 37 and 29 months, respectively, with lower incidence of coronary revascularization (HR 0.85; 95% CI 0.73-0.98; P = .029), heart failure (HR 0.83; 95% CI 0.72-0.97; P = .016), unstable angina (HR 0.78; 95% CI 0.64-0.96; P = .021), and CV death (HR 0.61; 95% CI 0.41-0.90; P = .014) with PDE-5i exposure. Phosphodiesterase type 5 inhibitor-exposed men had a 25% lower incidence of overall mortality (HR 0.75; 95% CI 0.65-0.87; P < .001). Men without coronary artery disease (CAD) but with CV risk factors at baseline showed a similar pattern. In the main study cohort, men in the highest quartile of PDE-5i exposure had the lowest incidence of MACE (HR 0.45; 95% CI 0.37-0.54; P < .001) and overall mortality (HR 0.51; 95% CI 0.37-0.71; P < .001) vs the lowest exposure quartile. In a subgroup with baseline type 2 diabetes (n = 6503), PDE-5i exposure was associated with a lower MACE risk (HR 0.79; 95% CI 0.64-0.97; P = .022). CLINICAL IMPLICATIONS: PDE-5is may have cardioprotective effects. STRENGTHS AND LIMITATIONS: Strengths are the large numbers of participants and consistency of the data; limitations include the retrospective nature of the study and unknown confounders. CONCLUSIONS: In a large population of US men with ED, PDE-5i exposure was associated with lower incidence of MACE, CV death, and overall mortality risk compared to non-exposure. Risk reduction correlated with PDE-5i exposure level.

Scoring and Interpretation of the FSFI: What can be Learned From 20 Years of use?

INTRODUCTION: Over the past 20 years, the Female Sexual Function Index (FSFI) has been considered the gold standard for the measurement of sexual function in women, with over 1,000 published manuscripts citing the article. Despite the measure's widespread usage and excellent psychometric properties, there has been some confusion over how to best implement and score the measure and interpret corresponding findings. AIM: The aim of the current article is to provide guidance, drawing from 20 years of use, on how to best implement the FSFI in research settings and interpret results based on the validation studies that have been conducted to date. METHODS: The overview of scoring and interpretation procedures found in this article is drawn from a review of the published literature on the psychometric properties of the FSFI. MAIN OUTCOME MEASURE: The measure of interest for the present review is the FSFI. RESULTS: This review article provides information about implementing, scoring, and interpreting the full-scale FSFI. Domain-level scoring and interpretation procedures are also discussed across the 5 domains of the FSFI: arousal, satisfaction, desire, pain, and lubrication. Additionally, guidance is provided for evaluating translated versions of the FSFI and using the measure to examine sexual function in culturally diverse populations. CLINICAL IMPLICATIONS: Guidance on appropriately scoring and interpretating the FSFI has the potential to strengthen our empirical understanding of sexual function, and consequently, to guide theory-driven treatment development and clinical practice. STRENGTH & LIMITATIONS: The present review provides applied guidance for the appropriate use of the FSFI specifically, but does not cover other common measures of sexual function or adaptations of the original measure. CONCLUSION: It is our hope that the guidance found in this review will ultimately lead to more rigorous and appropriate usage of the FSFI in research settings. Meston CM, Freihart BK, Handy AB, et al. Scoring and Interpretation of the FSFI: What can be Learned From 20 Years of use? J Sex Med 2020;17:17-25.

Men's Sexual Health Questionnaire score changes vs spontaneous sexual adverse event reporting in men treated with dutasteride/tamsulosin combination therapy for lower urinary tract symptoms secondary to benign prostatic hyperplasia: A post hoc analysis of a prospective, randomised, placebo-controlled study.

AIM: To assess the impact of baseline characteristics on Men's Sexual Health Questionnaire (MSHQ) total scores and to evaluate the clinical relevance of MSHQ changes and their association with spontaneously reported sexual adverse events (SexAEs) in patients with benign prostatic hyperplasia. METHODS: This was a post hoc analysis of the Phase 4 FDC116115 study, in which patients aged ≥50 years were randomised 1:1 to receive a fixed-dose combination of dutasteride 0.5 mg and tamsulosin 0.4 mg (DUT-TAM FDC), or placebo. End-points included: change in MSHQ total scores by baseline characteristics and SexAEs; cumulative distribution function for change from baseline to month 12 in MSHQ total score and the ejaculation, erection, satisfaction and sexual desire (libido) domain scores; and relationship between changes in MSHQ scores and SexAEs. RESULTS: The intent-to-treat population comprised 489 patients (DUT-TAM FDC, n = 243; placebo, n = 246). The mean reduction in total MSHQ score was greater in patients with SexAEs across both groups, compared with patients without SexAEs. Most patients reporting any SexAE (86% DUT-TAM FDC, 67% placebo) had a worsening of the MSHQ total score at month 12 compared with baseline. Specifically, 90% (DUT-TAM FDC) and 75% (placebo) of patients reporting an ejaculation SexAE and 73% (DUT-TAM FDC) and 87% (placebo) of patients reporting an erection SexAE had a worsening of MSHQ ejaculation and erection domain scores, respectively, at month 12. A threshold effect for incident SexAE was observed; patients showing a decrease of approximately 6-10 points in the total MSHQ score were more likely to report SexAEs. CONCLUSION: Findings support the clinical utility of the MSHQ tool in assessing the impact of DUT-TAM on sexual function by linking numerical changes in MSHQ scores to spontaneously reported SexAEs for the first time. The threshold effect for incidence of SexAEs warrants further investigation to determine its clinical relevance.

Randomized Controlled Trial of a Web-Based Intervention to Disseminate Clinical Practice Guidelines for Posttraumatic Stress Disorder: The PTSD Clinicians Exchange.

Delivery of best-practice care for posttraumatic stress disorder (PTSD) is a priority for clinicians working with active duty military personnel and veterans. The PTSD Clinicians Exchange, an Internet-based intervention, was designed to assist in disseminating clinically relevant information and resources that support delivery of key practices endorsed in the Veterans Administration (VA)-Department of Defense (DoD) Clinical Practice Guidelines (CPG) for the Management of Posttraumatic Stress. We conducted a randomized controlled trial to examine the effectiveness of the Clinicians Exchange intervention in increasing familiarity and perceived benefits of 26 CPG-related and emerging practices. The intervention consisted of ongoing access to an Internet resource featuring best-in-class resources for practices, self-management of burnout, and biweekly e-mail reminders highlighting selected practices. Mental health clinicians (N = 605) were recruited from three service sectors (VA, DoD, community); 32.7% of participants assigned to the Internet intervention accessed the site to view resources. Individuals who were offered the intervention increased their practice familiarity ratings significantly more than those assigned to a newsletter-only control condition, d = 0.27, p = .005. From baseline to 12-months, mean familiarity ratings of clinicians in the intervention group increased from 3.0 to 3.4 on scale of 1 (not at all) to 5 (extremely); mean ratings for the control group were 3.2 at both assessments. Clinicians generally viewed the CPG practices favorably, rating them as likely to benefit their clients. The results suggest that Internet-based resources may aid more comprehensive efforts to disseminate CPGs, but increasing clinician engagement will be important.

Effects of Testosterone Treatment in Older Men.

BACKGROUND: Serum testosterone concentrations decrease as men age, but benefits of raising testosterone levels in older men have not been established. METHODS: We assigned 790 men 65 years of age or older with a serum testosterone concentration of less than 275 ng per deciliter and symptoms suggesting hypoandrogenism to receive either testosterone gel or placebo gel for 1 year. Each man participated in one or more of three trials--the Sexual Function Trial, the Physical Function Trial, and the Vitality Trial. The primary outcome of each of the individual trials was also evaluated in all participants. RESULTS: Testosterone treatment increased serum testosterone levels to the mid-normal range for men 19 to 40 years of age. The increase in testosterone levels was associated with significantly increased sexual activity, as assessed by the Psychosexual Daily Questionnaire (P<0.001), as well as significantly increased sexual desire and erectile function. The percentage of men who had an increase of at least 50 m in the 6-minute walking distance did not differ significantly between the two study groups in the Physical Function Trial but did differ significantly when men in all three trials were included (20.5% of men who received testosterone vs. 12.6% of men who received placebo, P=0.003). Testosterone had no significant benefit with respect to vitality, as assessed by the Functional Assessment of Chronic Illness Therapy-Fatigue scale, but men who received testosterone reported slightly better mood and lower severity of depressive symptoms than those who received placebo. The rates of adverse events were similar in the two groups. CONCLUSIONS: In symptomatic men 65 years of age or older, raising testosterone concentrations for 1 year from moderately low to the mid-normal range for men 19 to 40 years of age had a moderate benefit with respect to sexual function and some benefit with respect to mood and depressive symptoms but no benefit with respect to vitality or walking distance. The number of participants was too few to draw conclusions about the risks of testosterone treatment. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT00799617.).

Evaluation of the impact of dutasteride/tamsulosin combination therapy on libido in sexually active men with lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH): A post hoc analysis of a prospective randomised placebo-controlled study.

AIMS: Five-α reductase inhibitor (5ARI) therapy has been associated with sexual dysfunction in some patients. This study assessed the impact of a fixed-dose combination of the 5ARI dutasteride 0.5 mg and the α1 -adrenoceptor antagonist tamsulosin 0.4 mg (DUT-TAM FDC) on Men's Sexual Health Questionnaire (MSHQ) domain scores in patients with lower urinary tract symptoms secondary to benign prostatic hyperplasia (BPH). METHODS: This was a post hoc analysis of a double-blind, randomised, placebo-controlled, parallel-group, multicentre study in sexually active patients, aged ≥50 years, with a confirmed clinical diagnosis of BPH. Sexual activity, sexual desire, and bother domain scores of the MSHQ were assessed at baseline and at Months 1, 3, 6, 9, and 12. Correlation between MSHQ sexual activity/desire scores and ejaculation, erection, and satisfaction domains at baseline was also evaluated. RESULTS: In the intent-to-treat population (N = 489), 243 and 246 patients were randomised to DUT-TAM FDC and placebo groups, respectively. Compared with placebo, DUT-TAM FDC therapy resulted in statistically significant reductions (worsening) from baseline in adjusted mean MSHQ sexual activity and bother domain scores at Months 1, 3, 6, 9, and 12 (all P < 0.05) and in adjusted mean MSHQ sexual desire domain scores at Months 6, 9, and 12 (all P < 0.05). Significant moderate correlations in the expected direction were observed at baseline between the sexual activity/desire domains and the ejaculation, erection, and satisfaction domains (P < 0.0001). CONCLUSIONS: These findings help clarify the degree and impact of libido changes in sexually active men treated with DUT-TAM FDC and may support clinical decision-making.

An Empirical Crosswalk for the PTSD Checklist: Translating DSM-IV to DSM-5 Using a Veteran Sample.

The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) introduced numerous revisions to the fourth edition's (DSM-IV) criteria for posttraumatic stress disorder (PTSD), posing a challenge to clinicians and researchers who wish to assess PTSD symptoms continuously over time. The aim of this study was to develop a crosswalk between the DSM-IV and DSM-5 versions of the PTSD Checklist (PCL), a widely used self-rated measure of PTSD symptom severity. Participants were 1,003 U.S. veterans (58.7% with PTSD) who completed the PCL for DSM-IV (the PCL-C) and DSM-5 (the PCL-5) during their participation in an ongoing longitudinal registry study. In a randomly selected training sample (n = 800), we used equipercentile equating with loglinear smoothing to compute a "crosswalk" between PCL-C and PCL-5 scores. We evaluated the correspondence between the crosswalk-determined predicted scores and observed PCL-5 scores in the remaining validation sample (n = 203). The results showed strong correspondence between crosswalk-predicted PCL-5 scores and observed PCL-5 scores in the validation sample, ICC = .96. Predicted PCL-5 scores performed comparably to observed PCL-5 scores when examining their agreement with PTSD diagnosis ascertained by clinical interview: predicted PCL-5, κ = 0.57; observed PCL-5, κ = 0.59. Subsample comparisons indicated that the crosswalk's accuracy did not differ across characteristics including gender, age, racial minority status, and PTSD status. The results support the validity of this newly developed PCL-C to PCL-5 crosswalk in a veteran sample, providing a tool with which to interpret and translate scores across the two measures.

Spanish Abstracts by Asociación Chilena de Estrés Traumático (ACET) Un cruce empírico para la lista de verificación de TEPT: traducción de DSM-IV a DSM-5 utilizando una muestra de veteranos CRUCE PARA LA LISTA DE VERIFICACIÓN DEL TEPT La quinta edición del Manual Diagnóstico y Estadístico de los Trastornos Mentales (DSM-5) introdujo numerosas revisiones a los criterios de la cuarta edición (DSM-IV) para el trastorno de estrés postraumático (TEPT), lo que representa un desafío para los médicos e investigadores que desean evaluar los síntomas de TEPT de manera continua a través del tiempo. El objetivo de este estudio fue desarrollar un cruce entre las versiones DSM-IV y DSM-5 de la Lista de verificación de TEPT (PCL en su sigla en inglés), una medida autoevaluada ampliamente utilizada de la gravedad de los síntomas de TEPT. Los participantes fueron 1.003 veteranos estadounidenses (58.7% con TEPT) que completaron el PCL para DSM-IV (PCL-C) y DSM-5 (PCL-5) durante su participación en un estudio de registro longitudinal en curso. En una muestra de entrenamiento seleccionada al azar (n = 800), utilizamos equipercentil equiparado con suavizado loglineal para calcular un "cruce" entre las puntuaciones PCL-C y PCL-5. Evaluamos la correspondencia entre las puntuaciones pronosticadas determinadas por el cruce y las puntuaciones PCL-5 observadas en la muestra de validación restante (n = 203). Los resultados mostraron una fuerte correspondencia entre los puntajes PCL-5 pronosticados para el cruce y los puntajes PCL-5 observados en la muestra de validación, ICC = .96. Los puntajes de PCL-5 pronosticados se compararon con los puntajes de PCL-5 observados al examinar su acuerdo con el diagnóstico de TEPT determinado por entrevista clínica: PCL-5 predicho, κ = 0.57; PCL-5 observado, κ = 0,59. Las comparaciones de submuestras indicaron que la precisión del cruce no difirió entre las características, incluidos el género, la edad, el estado de minoría racial y el estado de TEPT. Los resultados respaldan la validez de este paso de cruce recién desarrollado de PCL-C a PCL-5 en una muestra de veteranos, proporcionando una herramienta con la que interpretar y traducir las puntuaciones en las dos medidas.

Posttraumatic Stress Disorder Severity and Insomnia-Related Sleep Disturbances: Longitudinal Associations in a Large, Gender-Balanced Cohort of Combat-Exposed Veterans.

Few studies have investigated the range and severity of insomnia-related sleep complaints among veterans with posttraumatic stress disorder (PTSD), and the temporal association between insomnia and PTSD severity has yet to be examined. To examine these associations, a large, gender-balanced cohort of veterans (N = 1,649) of the Iraq and Afghanistan conflicts participated in longitudinal assessments of PTSD and insomnia-related symptoms over a period of 2.5 years following enrollment (range: 2-4 years). Data were obtained from multiple sources, including interviews, self-report assessments, and electronic medical record data. Three-fourths (74.0%) of veterans with PTSD diagnoses at Time 1 (T1) reported insomnia-related sleep difficulties on at least half the nights during the past 30 days, and one-third of participants had received a prescription for a sedative-hypnotic drug in the past year. Veterans without PTSD had fewer sleep problems overall, although the prevalence of sleep problems was high among all study participants. In longitudinal, cross-lagged panel models, the frequency of sleep problems at T1 independently predicted increases in PTSD severity at Time 2 (T2), B = 0.27, p < .001, after controlling for gender and relevant comorbidities. Conversely, T1 PTSD severity was associated with increasing sleep complaints at T2 but to a lesser degree, B = 0.04, p < .001. Moderately high rates of sedative-hypnotic use were seen in veterans with PTSD, with more frequent use in women compared to men (40.4% vs. 35.0%). Sleep complaints were highly prevalent overall and highlight the need for increased clinical focus on this area.

Spanish Abstracts by Asociación Chilena de Estrés Traumático (ACET) Gravedad del TEPT y Trastornos del Sueño Relacionados con el Insomnio: Asociaciones Longitudinales en una gran Cohorte, Balanceados por Género. de Veteranos Expuestos al Combate SUEÑO, INSOMNIO Y SEVERIDAD DE TEPT Pocos estudios han investigado el rango y la gravedad de las quejas del sueño relacionadas con el insomnio entre veteranos con trastorno de estrés postraumático (TEPT) y la asociación temporal entre el insomnio y la severidad del TEPT aún no se han examinado. Para examinar estas asociaciones, una gran cohorte de veteranos (N = 1,649) de los conflictos de Irak y Afganistán, balanceados por género, participaron en evaluaciones longitudinales de TEPT y síntomas relacionados con el insomnio durante un período de 2.5 años posteriores a la inscripción (rango: 2-4 años). Los datos se obtuvieron de múltiples fuentes, incluyendo entrevistas, autoevaluaciones y datos de registros médicos electrónicos. Tres cuartos (74.0%) de los veteranos con diagnóstico de TEPT en el tiempo 1 (T1) informaron dificultades de sueño relacionadas con el insomnio en al menos la mitad de las noches durante los últimos 30 días, y un tercio de los participantes habían recibido una prescripción de un fármaco sedante-hipnótico en el último año. Los veteranos sin TEPT tenían menos problemas de sueño en general, aunque la prevalencia de problemas de sueño fue alta entre todos los participantes del estudio. En los modelos longitudinales de panel con retardo cruzado, la frecuencia de los problemas de sueño en T1 predijeron independientemente aumentos en la severidad del TEPT en el Tiempo 2 (T2), B = 0.27, p <.001, después controlar por género y comorbilidades relevantes. Por el contrario, la gravedad del TEPT en T1 se asoció con un aumento de las quejas de sueño en T2 pero en menor grado, B = 0.04, p <.001. Se observaron tasas moderadamente altas de uso de hipnóticos-sedativos en veteranos con TEPT, con un uso más frecuente en mujeres comparadas con hombres (40.4% vs. 35.0%). En general las quejas de sueño fueron altamente prevalentes y destacan la necesidad de una mayor focalización clínica en esta área.

A prospective randomised placebo-controlled study of the impact of dutasteride/tamsulosin combination therapy on sexual function domains in sexually active men with lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH).

OBJECTIVE: To prospectively assess the impact of the fixed-dose combination (FDC) of the 5α-reductase inhibitor (5ARI), dutasteride 0.5 mg and the α1 -adrenoceptor antagonist, tamsulosin 0.4 mg (DUT-TAM FDC) therapy on sexual function domain scores in sexually active men with lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH), using the Men's Sexual Health Questionnaire (MSHQ). PATIENTS AND METHODS: This European and Australian double-blind, placebo-controlled, parallel-group study was conducted at 51 centres. INCLUSION CRITERIA: age ≥50 years, International Prostate Symptom Score ≥12, prostate volume ≥30 cc, prostate-specific antigen 1.5-10 ng/mL. Patients were randomised 1:1 to DUT-TAM FDC therapy or placebo for 12 months. The change from baseline to Month 12 on the total MSHQ (primary endpoint) and MSHQ erection, ejaculation and satisfaction domains (secondary outcome) was assessed, using a mixed model repeated measures analysis. Safety was evaluated. RESULTS: The intention-to-treat population included 489 patients (243 DUT-TAM FDC therapy; 246 placebo). A significant decrease (worsening) was observed with DUT-TAM FDC therapy versus placebo on the total MSHQ score (-8.7 vs -0.7; standard error [se]: 0.81, 0.78; P < 0.001), and the ejaculation (-7.5 vs -0.6; se: 0.56, 0.55; P < 0.001) and satisfaction (-0.6 vs +0.3; se: 0.3, 0.29, P = 0.047) domains, but not the erection domain (-1.0 vs -0.5; se: 0.19, 0.19, P = 0.091). CONCLUSION: This is the first domain-specific quantitative evaluation of DUT-TAM FDC therapy on sexual function in men with LUTS secondary to BPH. The observed changes in the MSHQ with DUT-TAM FDC therapy were mainly driven by changes in the ejaculation domain. These findings will help give context to erectile and ejaculatory dysfunction AEs reported spontaneously in earlier 5ARI studies.

Validity and Clinically Meaningful Changes in the Psychosexual Daily Questionnaire and Derogatis Interview for Sexual Function Assessment: Results From the Testosterone Trials.

BACKGROUND: Limited information is available on the performance characteristics of 2 questionnaires commonly used in clinical research, the Psychosexual Daily Questionnaire (PDQ) and the Derogatis Interview for Sexual Function (DISF)-II Assessment, especially in older men with low testosterone (T) and impaired sexual function. AIM: To determine reliability of PDQ and DISF-II by assessing the correlation within and between domains in the questionnaires and to define clinically meaningful changes in sexual activity (PDQ question 4 [Q4]) and desire (DISF-II sexual desire domain [SDD]) domains. METHODS: Data from 470 men participating in the T Trials were used to calculate Spearman correlation coefficients of individual items and total score among questionnaires to determine convergent and construct validity. Clinically meaningful changes for sexual desire and activity were determined by randomly dividing the sample into training and validation sets. Anchor- and distribution-based clinically meaningful change criteria were defined in the training set, and selected changes were evaluated in the validation set. OUTCOMES: Validity of the PDQ and DISF-II and clinically meaningful changes in sexual desire and activity were determined in older men in T Trials. RESULTS: Moderate to strong correlations were shown within and between domains from different questionnaires. Using Patient Global Impression of Change as an anchor, clinically meaningful change in PDQ sexual activity was ≥0.6, and in DISF-SDD was ≥5.0. Applying these change cut-points to the validation set, a greater proportion of T-treated men achieved clinically meaningful improvement in their sexual desire and activity compared to placebo-treated men. CLINICAL IMPLICATIONS: The PDQ-Q4 and DISF-II-SDD can be used to reliably assess clinically meaningful changes in sexual activity and sexual desire in hypogonadal men treated with T. STRENGTHS & LIMITATIONS: Strengths of this study include a large sample size, long trial duration, and inclusion of men with low libido and unequivocally low T levels. Limitations include using data from a single study that enrolled only older hypogonadal men, and only 1 anchor for both sexual desire and activity. CONCLUSION: Moderate to strong correlations were demonstrated within and between different sexual domains of the PDQ and DISF-II confirming construct and convergent validity. Clinically meaningful improvement in elderly hypogonadal men was change of ≥0.6 score in the PDQ-Q4 and ≥5.0 in the DISF-SDD. Improvements in sexual activity and desire in the T Trials were modest but clinically meaningful. Wang C, Stephens-Shields AJ, DeRogatis LR, et al. Validity and Clinically Meaningful Changes in the Psychosexual Daily Questionnaire and Derogatis Interview for Sexual Function Assessment: Results From the Testosterone Trials. J Sex Med 2018;15:997-1009.

A longitudinal study of risk factors for suicide attempts among Operation Enduring Freedom and Operation Iraqi Freedom veterans.

BACKGROUND: Suicide rates among veterans have increased markedly since the onset of Operations Enduring Freedom (OEF) and Iraqi Freedom (OIF; LeardMann et al., 2013). Identification of factors with the greatest contribution to suicide risk among veterans is needed to inform risk assessment and to identify intervention targets. METHODS: This study examined predictors of suicide attempts among participants in the Veterans After-Discharge Longitudinal Registry; a nationwide cohort of OEF/OIF veterans enrolled in Department of Veterans Affairs (VA) services. Veterans with and without probable posttraumatic stress disorder (PTSD) were sampled at a 3:1 ratio, and male and female veterans were sampled at a 1:1 ratio. Participants (N = 1,649) were assessed at two time points, roughly 2 years apart (M = 28.74 months, SD = 8.72). RESULTS: Seventy-four participants (4.49%) attempted suicide during the follow-up period. The strongest predictors of suicide attempts among the full sample were suicidal intent, attempt history, suicide ideation, PTSD symptoms, alcohol use disorder (AUD) symptoms, and depression. Veterans with multiple risk factors were particularly vulnerable; of veterans with 0, ≥1, ≥2, ≥3, or ≥ 4 of these risk factors, 0%, 7.81%, 10.31%, 18.45%, and 20.51% made a suicide attempt, respectively. CONCLUSIONS: This prospective study identified several strong predictors of suicide attempts among OEF/OIF veterans which may be important targets for suicide prevention efforts. Further, co-occurrence of multiple risk factors was associated with markedly greater risk for suicide attempts; veterans with multiple risk factors appear to be at the highest risk among OEF/OIF veterans enrolled in VA care.

Testosterone treatment is not associated with increased risk of prostate cancer or worsening of lower urinary tract symptoms: prostate health outcomes in the Registry of Hypogonadism in Men.

OBJECTIVES: To evaluate the effects of testosterone-replacement therapy (TRT) on prostate health indicators in hypogonadal men, including rates of prostate cancer diagnoses, changes in prostate-specific antigen (PSA) levels and lower urinary tract symptoms (LUTS) over time. PATIENTS AND METHODS: The Registry of Hypogonadism in Men (RHYME) is a multi-national patient registry of treated and untreated, newly-diagnosed hypogonadal men (n = 999). Follow-up assessments were performed at 3-6, 12, 24, and 36 months. Baseline and follow-up data collection included medical history, physical examination, blood sampling, and patient questionnaires. Prostate biopsies underwent blinded independent adjudication for the presence and severity of prostate cancer; PSA and testosterone levels were measured via local and central laboratory assays; and LUTS severity was assessed via the International Prostate Symptom Score (IPSS). Incidence rates per 100 000 person-years were calculated. Longitudinal mixed models were used to assess effects of testosterone on PSA levels and IPSS. RESULTS: Of the 999 men with clinically diagnosed hypogonadism (HG), 750 (75%) initiated TRT, contributing 23 900 person-months of exposure. The mean testosterone levels increased from 8.3 to 15.4 nmol/L in treated men, compared to only a slight increase from 9.4 to 11.3 nmol/L in untreated men. In all, 55 biopsies were performed for suspected prostate cancer, and 12 non-cancer related biopsies were performed for other reasons. Overall, the proportion of positive biopsies was nearly identical in men on TRT (37.5%) compared to those not on TRT (37.0%) over the course of the study. There were no differences in PSA levels, total IPSS, or the IPSS obstructive sub-scale score by TRT status. Lower IPSS irritative sub-scale scores were reported in treated compared to untreated men. CONCLUSIONS: Results support prostate safety of TRT in newly diagnosed men with HG.

The Natural History of Erectile Dysfunction After Prostatic Radiotherapy: A Systematic Review and Meta-Analysis.

BACKGROUND: Erectile dysfunction (ED) after treatment for prostate cancer with radiotherapy (RT) is well known, and pooled estimates of ED after RT will provide more accurate patient education. AIM: To systematically evaluate the natural history of ED in men with previous erectile function after prostate RT and to determine clinical factors associated with ED. METHODS: We performed a review of the PubMed and Medline, Embase, Cochrane Library, and Web of Science databases in April 2016 according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. Identified reports included a measurement of ED before and after prostate RT. Two hundred seventy-eight abstracts were screened and 105 publications met the criteria for inclusion. Only men with known erectile function before RT were included in the analysis. OUTCOME: ED after RT of the prostate. RESULTS: In total, 17,057 men underwent brachytherapy (65%), 8,166 men underwent external-beam RT (31%), and 1,046 men underwent both (4%). Seven common instruments were used to measure ED, including 23 different cutoffs for ED. The Sexual Health Inventory for Men (SHIM) was used in 31 studies (30%). Pooled estimates of SHIM-confirmed ED (score <10-17) suggested the prevalence of ED after RT is 34% of men (95% CI = 0.29-0.39) at 1 year and 57% (95% CI = 0.53-0.61) at 5.5 years. Compared with brachytherapy, studies of the two types of radiation increased the proportion of new-onset ED found by 12.3% of studies (95% CI = 2.3-22.4). For every 10% who were lost to follow-up, the proportion of ED reported increased by 2.3% (95% CI = 0.03-4.7). CLINICAL IMPLICATIONS: ED is common regardless of RT modality and increases during each year of follow-up. Using the SHIM, ED is found in approximately 50% patients at 5 years. STRENGTHS AND LIMITATIONS: The strengths of this systematic review include strict inclusion criteria of studies that measured baseline erectile function, no evidence for large effect size bias, and a large number of studies, which allow for modeling techniques. However, all data included in this analysis were observational, which leaves the possibility that residual confounding factors increase the rates of ED. CONCLUSION: Definitions and measurements of ED after RT vary considerably in published series and could account for variability in the prevalence of reported ED. Loss to follow-up in studies could bias the results to overestimate ED. Gaither TW, Awad MA, Osterberg EC, et al. The Natural History of Erectile Dysfunction After Prostatic Radiotherapy: A Systematic Review and Meta-Analysis. J Sex Med 2017;14:1071-1078.

Quality of Life and Sexual Function Benefits of Long-Term Testosterone Treatment: Longitudinal Results From the Registry of Hypogonadism in Men (RHYME).

BACKGROUND: The benefits and risks of long-term testosterone administration have been a topic of much scientific and regulatory interest in recent years. AIM: To assess long-term quality of life (QOL) and sexual function benefits of testosterone replacement therapy (TRT) prospectively in a diverse, multinational cohort of men with hypogonadism. METHODS: A multinational patient registry was used to assess long-term changes associated with TRT in middle-age and older men with hypogonadism. Comprehensive evaluations were conducted at 6, 12, 24, and 36 months after enrollment into the registry. OUTCOMES: QOL and sexual function were evaluated by validated measures, including the Aging Males' Symptom (AMS) Scale and the International Index of Erectile Function (IIEF). RESULTS: A total of 999 previously untreated men with hypogonadism were enrolled at 25 European centers, 750 of whom received TRT at at least one visit during the period of observation. Patients on TRT reported rapid and sustained improvements in QOL, with fewer sexual, psychological, and somatic symptoms. Modest improvements in QOL and sexual function, including erectile function, also were noted in RHYME patients not on TRT, although treated patients showed consistently greater benefit over time in all symptom domains compared with untreated patients. AMS total scores for patients on TRT were 32.8 (95% confidence interval = 31.3-34.4) compared with 36.6 (95% confidence interval = 34.8-38.5) for untreated patients (P < .001). Small but significant improvements in IIEF scores over time also were noted with TRT. Approximately 25% of treated and untreated men also used phosphodiesterase type 5 inhibitors, with notable differences in the frequency of phosphodiesterase type 5 inhibitor prescription use according to physician specialty and geographic site location. CLINICAL IMPLICATIONS: TRT-related benefits in QOL and sexual function are well maintained for up to 36 months after initiation of treatment. STRENGTHS AND LIMITATIONS: The major strengths are the large, diverse patient population being treated in multidisciplinary clinical settings. The major limitation is the frequency of switching from one formulation to another. CONCLUSION: Overall, we confirmed the broad and sustained benefits of TRT across major QOL dimensions, including sexual, somatic, and psychological health, which were sustained over 36 months in our treatment cohort. Rosen RC, Wu F, Behre H, et al. Quality of Life and Sexual Function Benefits Effects of Long-Term Testosterone Treatment: Longitudinal Results From the Registry of Hypogonadism in Men (RHYME). J Sex Med 2017;14:1104-1115.

Examining the diagnostic utility of the DSM-5 PTSD symptoms among male and female returning veterans.

BACKGROUND: Posttraumatic stress disorder (PTSD) diagnostic criteria have been criticized for including symptoms that overlap with commonly comorbid disorders, which critics argue undermines the validity of the diagnosis and inflates psychiatric comorbidity rates. In response, the upcoming 11th edition of the International Classification of Diseases (ICD-11) will offer PTSD diagnostic criteria that are intended to promote diagnostic accuracy. However, diagnostic utility analyses have not yet assessed whether these criteria minimize diagnostic errors. The present study examined the diagnostic utility of each PTSD symptom in the fifth edition of the Diagnostic and Statistical Manual for Mental Disorders (DSM-5) for males and females. METHODS: Participants were 1,347 individuals enrolled in a longitudinal national registry of returning veterans receiving care at a Department of Veterans Affairs (VA) facility. Doctoral level clinicians assessed all participants using the PTSD module of the Structured Clinical Interview for DSM. RESULTS: Of the 20 symptoms examined, the majority performed in the fair to poor range on test quality indices. Although a few items did perform in the good (or better) range, only half were ICD-11 symptoms. None of the 20 symptoms demonstrated good quality of efficiency. Results demonstrated few sex differences across indices. There were no differences in the proportion of comorbid psychiatric disorders or functional impairment between DSM-5 and ICD-11 criteria. CONCLUSIONS: ICD-11 PTSD criteria demonstrate neither greater diagnostic specificity nor reduced rates of comorbidity relative to DSM-5 criteria and, as such, do not perform as intended. Modifications to existing symptoms or new symptoms may improve differential diagnosis.

A longitudinal examination of peritraumatic emotional responses and their association with posttraumatic stress disorder and major depressive disorder among veterans.

Research has revealed a significant association between several peritraumatic emotional responses and posttraumatic stress disorder (PTSD). Preliminary research has also linked peritraumatic emotional responses with a diagnosis of major depressive disorder (MDD). The majority of this research has been cross-sectional, thereby making it difficult to determine the extent to which the various peritraumatic emotional responses may increase risk for, or serve as a premorbid marker of, PTSD and MDD. This study examined the longitudinal role of peritraumatic emotional responses on the subsequent development of PTSD and MDD in a sample of US military veterans. Whereas a number of peritraumatic emotional responses were concurrently associated with PTSD, only peritraumatic numbness maintained the association with this diagnosis longitudinally. For MDD, peritraumatic numbness was the only emotional response related to the diagnosis both concurrently and longitudinally. Study findings are a preliminary proof of concept that peritraumatic numbness may serve as a premorbid marker for the development of PTSD and MDD following a traumatic event. Implications of these findings for the diagnosis, assessment, and treatment of both PTSD and MDD are discussed.

Erectile dysfunction and lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH) combined responders to tadalafil after 12 weeks of treatment.

OBJECTIVE: To analyse the proportion of men taking tadalafil 5 mg once daily who experience a combined improvement in symptoms of both erectile dysfunction (ED) and lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH). MATERIALS AND METHODS: The data from men aged ≥45 years randomized to tadalafil 5 mg once daily or placebo enrolled in one of four randomized, placebo-controlled LUTS/BPH clinical trials were analysed (N = 927). A novel classification of 'combined responders' to ED and LUTS/BPH treatment was defined, based on published criteria for men who showed improvement in both International Index of Erectile Function - Erectile Function domain (IIEF-EF) score and total International Prostate Symptom Score (IPSS). Descriptive analyses assessed the covariate distribution by responder status. Unadjusted and adjusted logistic regressions provided odds ratios with 95% confidence intervals comparing combined responders with all others (partial and non-responders). RESULTS: Among men randomized to tadalafil 5 mg, 40.5% were combined responders (n = 189). Among placebo randomized men, 18.3% were combined responders (n = 84). Combined responders, in the total population, had the highest baseline IPSS and lowest baseline IIEF-EF scores, corresponding to the highest level of dysfunction. The majority of men were aged ≤65 years, white, non-obese, non-smokers, and regular alcohol consumers. Only treatment, baseline IPSS, baseline IIEF-EF, obesity and psychoactive medication use were significantly associated with responder status (P ≤ 0.05). Tadalafil-treated men had 2.8 times significantly increased adjusted odds of being combined responders vs non-responders (P < 0.001). For each unit decrease in baseline IIEF-EF or alcoholic drink consumption per week there was a 4% significant increase in the adjusted odds of being a combined responder to tadalafil therapy. CONCLUSIONS: This novel measure of combined response is useful in differentiating patients with clinically relevant symptom improvement for both ED and LUTS/BPH after treatment with tadalafil 5 mg once daily vs placebo. This combined responder measure may be useful in future assessment of treatment benefits across patient groups after various types of treatment intervention (e.g. surgical vs pharmacotherapy vs non-pharmacological intervention).

Diagnosing Sexual Dysfunction in Men and Women: Sexual History Taking and the Role of Symptom Scales and Questionnaires.

INTRODUCTION: A detailed sexual history is the cornerstone for all sexual problem assessments and sexual dysfunction diagnoses. Diagnostic evaluation is based on an in-depth sexual history, including sexual and gender identity and orientation, sexual activity and function, current level of sexual function, overall health and comorbidities, partner relationship and interpersonal factors, and the role of cultural and personal expectations and attitudes. AIM: To propose key steps in the diagnostic evaluation of sexual dysfunctions, with special focus on the use of symptom scales and questionnaires. METHODS: Critical assessment of the current literature by the International Consultation on Sexual Medicine committee. MAIN OUTCOME MEASURES: A revised algorithm for the management of sexual dysfunctions, level of evidence, and recommendation for scales and questionnaires. RESULTS: The International Consultation on Sexual Medicine proposes an updated algorithm for diagnostic evaluation of sexual dysfunction in men and women, with specific recommendations for sexual history taking and diagnostic evaluation. Standardized scales, checklists, and validated questionnaires are additional adjuncts that should be used routinely in sexual problem evaluation. Scales developed for specific patient groups are included. Results of this evaluation are presented with recommendations for clinical and research uses. CONCLUSION: Defined principles, an algorithm and a range of scales may provide coherent and evidence based management for sexual dysfunctions.

Men with Sexual Problems and Their Partners: Findings from the International Survey of Relationships.

Epidemiologic studies of sexual function problems in men have focused on the individual male and related sociodemographic characteristics, individual risk factors and lifestyle concomitants, or medical comorbidities. Insufficient attention has been given to the role of sexual and relationship satisfaction and, more particularly, to the perspective of the couple as causes or correlates of sexual problems in men or women. Previously, we reported results of the first large, multi-national study of sexual satisfaction and relationship happiness in 1,009 midlife and older couples in five countries (Brazil, Germany, Japan, Spain, U.S.). For the present study, we examined, within each problem, the association of four major sexual problems in men (loss of sexual desire, erectile problems, premature ejaculation, delayed/absent orgasm) and multiple problems, with male and female partners' assessments of physical intimacy, sexual satisfaction, and relationship happiness, as well as associations with well-known health and psychosocial correlates of sexual problems in men. Sexual problem rates of men in our survey were generally similar to rates observed in past surveys in the general population, and similar risk factors (age, relationship duration, overall health) were associated with lack of desire, anorgasmia, or erection difficulties in our sample. As in previous surveys, there were few correlates of premature ejaculation. As predicted, men with one or more sexual problems reported decreased relationship happiness as well as decreased sexual satisfaction compared to men without sexual problems. Moreover, female partners of men with sexual problems had reduced relationship happiness and sexual satisfaction, although these latter outcomes were less affected in the women than the men. The association of men's sexual problems with men's and women's satisfaction and relationship happiness were modest, as these couples in long-term, committed relationships were notable for their relatively high levels of physical affection and relationship happiness.