Article
To read the full-text of this research, you can request a copy directly from the authors.

Abstract

Objectives: Recent literature reports inverse associations with ejaculator frequency and prostate cancer (PC). We sought to explore the relationship between ejaculatory frequency from ages 20 to 50 and subsequent development of aggressive PC. Material and methods: We conducted a case-control study sampling 2,141 men from private urology practices in Victoria, Australia. Cases were defined as men with high grade or high stage PC and controls being biopsy negative men. Ejaculation frequency recalled at age decades 20, 30, and 40 second was assessed by questionnaire. Unconditional multivariable logistic regression models were used to generate odds ratios (ORs). Results: An inverse association with ejaculatory frequency at age 30 to 39 was observed (OR per 5-unit increase per week = 0.83, 95% CI: 0.72-0.96) but not at ages 20 to 29 (OR = 1.01, 95% CI: 0.89-1.14) or ages 40 to 49 (OR = 0.95, 95% CI: 0.81-1.12). This result differed between men with new sexual partners after age 30 (OR = 0.77, P = 0.009) and those with no new partners (OR = 0.97, P = 0.8) though the test for a difference between these estimates was not significant (P = 0.11). Conclusion: We found only weak evidence of an inverse association between ejaculatory frequency in the fourth decade of life and advanced PC, which was not significantly modified by number of new sexual partners. No relationship was found for ejaculatory frequency in the third and fifth decades of life.

No full-text available

Request Full-text Paper PDF

To read the full-text of this research,
you can request a copy directly from the authors.

... The protective effect was maintained after adjustment for the number of male partners. The authors suggested that one plausible explanation could be a higher EF, which has been shown to decrease the risk of PCa [91,92]. Nonetheless, it has not been proved that EF is increasing with a higher number of female partners. ...
... Nonetheless, it has not been proved that EF is increasing with a higher number of female partners. EF has been proposed as a modifiable risk factor for PCa; this association has been studied recently by two research groups [91,92]. In a prospective cohort study, Rider et al [91] showed a decreased risk of low-grade PCa in patients with an EF of !21/mo at ages 20-29 and 40-49 yr. ...
... In a prospective cohort study, Rider et al [91] showed a decreased risk of low-grade PCa in patients with an EF of !21/mo at ages 20-29 and 40-49 yr. This observation was corroborated by Papa et al [92] in a CCS that showed an inverse association between PCa risk and EF at ages 30-39 yr when considering the OR per five-unit increase in ejaculation per week. ...
Article
Context: To date, established risk factors for prostate cancer (PCa) are limited to age, race, family history, and certain genetic polymorphisms. Despite great research efforts, available evidence on potentially modifiable risk factors is conflicting. Moreover, most studies on PCa risk factors did not consider the impact of prostate-specific antigen (PSA) testing on PCa diagnosis. Objective: To provide a detailed overview of the latest evidence on the role of metabolic diseases, drugs, and dietary factors for risk of PCa incidence, recurrence, and survival in men exposed to PSA testing. Evidence acquisition: A systematic review of the English-language literature was performed using the MEDLINE, Cochrane Central Register of Controlled Trials, and Web of Science databases according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses recommendations. Randomized, case-control, or cohort studies published during the periods 2008-2017 (on drugs and metabolic diseases) and 2003-2017 (on dietary factors), with extensive follow-up (≥8-10yr for studies on PCa risk; ≥2-5yr for studies on PCa recurrence, progression, and survival, depending on the review subtopic) and adjusting of the analyses, beyond established risk factors, for either rate of PSA testing (for risk analyses) or PCa stage and primary treatment (for survival analyses), were eligible for inclusion. Evidence synthesis: Overall, 39 reports from 22 observational studies were included. Studies were heterogeneous regarding definitions of exposure or outcomes, length of follow-up, risk of bias, and confounding. For some risk factors, evidence was insufficient to assess potential effects, while for others there was no evidence of an effect. For selected risk factors, namely metformin, aspirin and statin use, diabetes, obesity, and specific dietary intakes, there was low-quality evidence of modest effects on PCa risk. Conclusions: Current evidence from long-term observational studies evaluating the effect of drugs, metabolic diseases, and dietary factors for PCa risk considering the impact of PSA testing is still not conclusive. Future research is needed to confirm the associations suggested by our review, exploring their potential biological explanations and selecting those risk factors most likely to trigger effective public health interventions. Patient summary: We reviewed the available studies published in the recent literature on the potential role of drugs, metabolic diseases, and food and dietary factors for the risk of prostate cancer, considering the impact of prostate-specific antigen testing on prostate cancer diagnosis. We found that for some factors data are currently insufficient to make definitive conclusions, while for others available studies seem to indicate an effect on the risk of prostate cancer.
... Further assessment of eligibility, based on full-text articles, led to the exclusion of 287 papers. Finally, 19 studies involving a total of 953,704 patients were included in the final analysis [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] (Figure 1). The main characteristics of the selected studies are summarized in Table 1, and the assessment of the risk of bias is reported in Figures 2 and 3. ...
... Papa et al. described an inverse association between EF and PCa at age 30 to 39 (OR per 5-unit increase per week 0.83, 95% CI: 0.72-0.96) but not at ages 20 to 29 or 40 to 49 [14]. Several hypotheses were proposed to explain the correlation between EF and PCa. ...
Article
Full-text available
Most cancers are related to lifestyle and environmental risk factors, including smoking, alcohol consumption, dietary habits, and environment (occupational exposures). A growing interest in the association between sexual activity (SA) and the development of different types of tumors in both men and women has been recorded in recent years. The aim of the present systematic review is to describe and critically discuss the current evidence regarding the association between SA and male genital cancers (prostatic, penile, and testicular), and to analyze the different theories and biological mechanisms reported in the literature. A comprehensive bibliographic search in the MEDLINE, Scopus, and Web of Science databases was performed in July 2021. Papers in the English language without chronological restrictions were selected. Retrospective and prospective primary clinical studies, in addition to previous systematic reviews and meta-analyses, were included. A total of 19 studies, including 953,704 patients were selected. Case reports, conference abstracts, and editorial comments were excluded. Men with more than 20 sexual partners in their lifetime, and those reporting more than 21 ejaculations per month, reported a decreased risk of overall and less aggressive prostate cancer (PCa). About 40% of penile cancers (PCs) were HPV-associated, with HPV 16 being the dominant genotype. Data regarding the risk of HPV in circumcised patients are conflicting, although circumcision appears to have a protective role against PC. Viral infections and epididymo-orchitis are among the main sex-related risk factors studied for testicular cancer (TC); however, data in the literature are limited. Testicular trauma can allow the identification of pre-existing TC. SA is closely associated with the development of PC through high-risk HPV transmission; in this context, phimosis appears to be a favoring factor. Sexual behaviors appear to play a significant role in PCa pathogenesis, probably through inflammatory mechanisms; however, protective sexual habits have also been described. A direct correlation between SA and TC has not yet been proven, although infections remain the most studied sex-related factor.
... Similar conclusions have been reported regarding STDs [144,145]. However, some studies report a beneficial role of more frequent ejaculation in adulthood, particularly for low-risk PCa [13,146,147]. ...
Article
Full-text available
Prostate cancer (PCa) is one of the most common cancers among men, and its incidence has been rising through the years. Several risk factors have been associated with this disease and unhealthy lifestyles and inflammation were appointed as major contributors for PCa development, progression, and severity. Despite the advantages associated with the currently used diagnostic tools [prostate-specific antigen(PSA) serum levels and digital rectal examination (DRE)], the development of effective approaches for PCa diagnosis is still necessary. Finding lifestyle-associated proteins that may predict the development of PCa seems to be a promising strategy to improve PCa diagnosis. In this context, several biomarkers have been identified, including circulating biomarkers (CRP, insulin, C-peptide, TNFα-R2, adiponectin, IL-6, total PSA, free PSA, and p2PSA), urine biomarkers (PCA3, guanidine, phenylacetylglycine, and glycine), proteins expressed in exosomes (afamin, vitamin D-binding protein, and filamin A), and miRNAs expressed in prostate tissue (miRNA-21, miRNA-101, and miRNA-182). In conclusion, exploring the impact of lifestyle and inflammation on PCa development and progression may open doors to the identification of new biomarkers. The discovery of new PCa diagnostic biomarkers should contribute to reduce overdiagnosis and overtreatment.
... Participants to this study came from (i) the Melbourne Collaborative Cohort Study (MCCS), (ii) the Aggressive Prostate Cancer (APC) study, (iii) the Risk Factors for Prostate Cancer Study (RFPCS), (iv) the Early-Onset Prostate Cancer Family Study (EOPCFS), and (v) the ASPirin in Reducing Events in the Elderly (ASPREE) study. The MCCS, APC, RFPCS, and EOPCFS are Australian research studies of prostate cancer that have been described previously [32][33][34]. The ASPREE study is a randomized, placebo-controlled trial for daily low-dose aspirin. ...
Article
Full-text available
While gene panel sequencing is becoming widely used for cancer risk prediction, its clinical utility with respect to predicting aggressive prostate cancer (PrCa) is limited by our current understanding of the genetic risk factors associated with predisposition to this potentially lethal disease phenotype. This study included 837 men diagnosed with aggressive PrCa and 7261 controls (unaffected men and men who did not meet criteria for aggressive PrCa). Rare germline pathogenic variants (including likely pathogenic variants) were identified by targeted sequencing of 26 known or putative cancer predisposition genes. We found that 85 (10%) men with aggressive PrCa and 265 (4%) controls carried a pathogenic variant (p < 0.0001). Aggressive PrCa odds ratios (ORs) were estimated using unconditional logistic regression. Increased risk of aggressive PrCa (OR (95% confidence interval)) was identified for pathogenic variants in BRCA2 (5.8 (2.7–12.4)), BRCA1 (5.5 (1.8–16.6)), and ATM (3.8 (1.6–9.1)). Our study provides further evidence that rare germline pathogenic variants in these genes are associated with increased risk of this aggressive, clinically relevant subset of PrCa. These rare genetic variants could be incorporated into risk prediction models to improve their precision to identify men at highest risk of aggressive prostate cancer and be used to identify men with newly diagnosed prostate cancer who require urgent treatment.
... Ces résultats sont, cependant, en contradiction avec ceux de la méta-analyse de Jian et al. (2018) pour qui c'est une fréquence modérée d'éjaculation (2 à 4 fois par semaine) qui est associée à une diminution significative du risque de cancer de la prostate (Jian, Ye, Chen, Li, & Wang, 2018). D'autre part, une étude ne retrouve pas d'association significative entre la fréquence d'éjaculation au cours de la quatrième décennie de vie et le cancer avancé de 39 la prostate (Papa et al., 2017). En termes de mécanisme de fonctionnement, il est envisagé qu'une éjaculation fréquente altère la fonction des cellules épithéliales de la zone périphérique de la glande prostatique pouvant être à l'origine de la tumorigenèse de la prostate (Costello & Franklin, 2006). ...
Thesis
Le cancer est désormais considéré comme une maladie chronique touchant une population toujours croissante. Une prise en charge et un suivi à long terme, à l’origine d’un bouleversement de la vie des patients et de leur entourage, semblent nécessaires et sont susceptibles d’initier une réorganisation du système de santé. Dans ce travail de thèse interdisciplinaire, nous nous sommes intéressés à l’impact du cancer sur le vécu psychologique et psychosocial des patients en France, en choisissant le modèle du cancer de la prostate. Pour cela, nous avons souhaité combiner deux études. L’une portait sur l’état de santé sexuelle des patients atteints d’un cancer de la prostate via une approche quantitative descriptive basée sur les données représentatives des enquêtes nationales VICAN. L’autre visait à déterminer l’impact du cancer de la prostate sur le couple et sa qualité de vie via une approche compréhensive qualitative complémentaire, focalisée sur une prise en charge en Surveillance Active et basée sur des entretiens semi-directifs de patients et de leurs conjointes. L’analyse des données a permis de montrer une détérioration de la santé sexuelle des patients, selon différents déterminants non nécessairement médicaux, et un endommagement du couple et des relations affectives perçues, avec des stratégies d’ajustements divergentes pour chacun des membres du couple, malgré une prise en charge initialement considérée comme optimale et indemne de conséquences. Une approche pluridisciplinaire pourrait permettre un accompagnement complet des couples pour une amélioration de leurs vécus, de leur bien-être et de leur qualité de vie
... 42 Other studies have found similar findings. 43,44 Potential explanations are given by the hormone-dependency of both sexual activity, including libido and prostate cancer or the concept of prostatic carcinogenesis involving the luminal fluid, prostatic tissue interaction. 45 Finally, it is possible that early symptoms of diseases may predict a decline in sexual activity before the diagnosis of the condition. ...
Article
Background Sexual activity can be referred to as a health behavior and may also act as an indicator of health status. Aim To evaluate temporal trends in sexual activity and to examine associations of sexual activity with all-cause and cause-specific mortality risk. Methods We examined the trends and prevalence of sexual activity and association of sexual activity with all-cause and cause-specific mortality in a nationally representative sample using data from the US National Health and Nutrition Examination Survey from 2005 to 2016 and the National Health and Nutrition Examination Survey 2005-2014 Linked Mortality File (through December 31, 2015). Outcomes All-cause, cardiovascular disease, and cancer mortality. Results A total of 15,269 US adults (mean age, 39.1 years [standard error, 0.18 years]) were included in the trend analysis. In the 2015-2016 cycle, while 71.7% (95% CI, 67.7–75.7%) US adults aged 20-59 years engaged in sexual activity ≥ 12 times/year (monthly), only 36.1% (95% CI, 31.6–40.7%) of them engaged in sexual activity ≥ 52 times/year (weekly). Since the 2005–2006 cycle, the estimated prevalence of sexual activity, ≥52 times/year and ≥12 times/year, were both stable over time among overall and each age group (all P for trend >0.1). During a median follow-up of 5.7 years (range, 1–11 years) and 71,960 person-years of observation, among 12,598 participants with eligible information on mortality status, 228 deaths occurred, including 29 associated with cardiovascular disease and 62 associated with cancer. Overall, participants with higher sexual activity frequency were at a lower risk of all-cause death in a dose-response manner (P for trend = 0.020) during the follow-up period. In addition, the multivariable-adjusted hazard ratios for all-cause mortality, CVD mortality, cancer mortality, and other cause mortality among participants who had sex ≥52 times/year compared with those having sex 0–1 time/year were 0.51 (95% CI, 0.34 to 0.76), 0.79 (95% CI, 0.19 to 3.21), 0.31 (95% CI, 0.11 to 0.84), and 0.52 (95% CI, 0.28 to 0.96), respectively. Clinical Implications Sexual activity appears to be a health indicator of all-cause and cancer mortality in US middle-aged adults. Strengths & Limitations Clear strengths of the present study include the large representative sample of the noninstitutionalized US population as well as the identification of precise estimates in relation to sexual activity and mortality. However, because of the observational nature of the study design, causality could not be determined. Conclusions Sexual activity was found to be associated with a lower risk of mortality from all cause and cancer. Cao C, Yang L, Xu T, et al. Trends in Sexual Activity and Associations With All-Cause and Cause-Specific Mortality Among US Adults. J Sex Med 2020;XX:XXX–XXX.
... A major study of 2016 that involved almost 32,000 men revealed that men who ejaculated ≥ 21 times per month (EPM) had about a 20% lower chance of low-grade prostate cancer, compared with those who had ≤ 4 -7 EPM based on 18 years follow-up [331]. A year later, a case-control study sampling a smaller group of men (2,141) from age 20 to 50 found only weak evidence of an inverse association between ejaculatory frequency in the fourth decade of life and advanced prostate cancer, which was not significantly modified by a number of new sexual partners [332]. In the same study, no relationship was found for ejaculatory frequency in the third and fifth decades of life. ...
Article
Full-text available
Prostate cancer is the second most frequent cancer diagnosis made in men and the fifth leading cause of death worldwide. Prostate cancer may be asymptomatic at the early stage and often has an indolent course that may require only active surveillance. Based on GLOBOCAN 2018 estimates, 1,276,106 new cases of prostate cancer were reported worldwide in 2018, with higher prevalence in the developed countries. Differences in the incidence rates worldwide reflect differences in the use of diagnostic testing. Prostate cancer incidence and mortality rates are strongly related to the age with the highest incidence being seen in elderly men (> 65 years of age). African-American men have the highest incidence rates and more aggressive type of prostate cancer compared to White men. There is no evidence yet on how to prevent prostate cancer; however, it is possible to lower the risk by limiting high-fat foods, increasing the intake of vegetables and fruits and performing more exercise. Screening is highly recommended at age 45 for men with familial history and African-American men. Up-to-date statistics on prostate cancer occurrence and outcomes along with a better understanding of the etiology and causative risk factors are essential for the primary prevention of this disease.
Article
Full-text available
Background: The incidence of prostate cancer in Cameroon has been increasing in an alarming rate. The aim of this study is to characterize the form of prostate cancer and associated factors in patients from Cameroon Northern Regions. Methods: All patients with positive prostate biopsy (cancer+) from June 2018 to November 2019 were studied (n = 177). The followings were retrieved: digital rectal examination, standard clinical examinations, laboratory data such as serum prostate-specific antigen (PSA) level, and the Gleason score. Patients self-administered a questionnaire assessing prostate cancer's risk factors. Results: Patients were mainly from the Far North region (36.72%), and were either farmers or breeders (48.01%). Only prostate ade-nocarcinoma was present, with predominance of aggressive forms (Gleason score ≥ 7). Significant relationships were observed between Gleason score and 1) patients' age (P = 0.006), 2) history of urinary tract infections (P = 0.015) and of exposure to agricultural products (P = 0.049), 3) clinical signs (nyctu-ria, pollakiuria, poor acute urine retention, and dysuria) (P = 0.019), 4) pros-tate weight, and 5) serum PSA levels (P < 0.0001). Conclusion: Aggressive forms of adenocarcinoma are the main prostate cancer in these regions, underlining the need for strategies aimed at raising prostate cancer awareness and early detection.
Article
The debate over the association between vasectomy and prostate cancer has been lasted about 40 years and there is no sign of stopping. In the present study, we aimed to evaluate whether vasectomy is associated with prostate cancer based on the most comprehensive and up-to-date evidence available. The PubMed, Cochrane Library, and EMBASE databases were systematically searched inception to March 14, 2021 without year or language restriction. Multivariable adjusted risk ratios (RRs) were used to assess each endpoint. Risk of bias was assessed using the Newcastle-Ottawa scale. A total of 58 studies involving 16,989,237 participants fulfilled inclusion criteria. There was significant association of vasectomy with risk of any prostate cancer (risk ratio, 1.18, 95% CI, 1.07–1.31). Association between vasectomy and advanced prostate cancer (risk ratio, 1.06, 95% CI, 1.01–1.12), low-grade prostate cancer (risk ratio, 1.06, 95% CI, 1.02–1.10), and intermediate-grade prostate cancer (risk ratio, 1.12, 95% CI, 1.03–1.22) were significant. There was no significant association between vasectomy and prostate cancer-specific mortality (risk ratio, 1.01, 95% CI, 0.93–1.10). This study found that vasectomy was associated with the risk of any prostate cancer and advanced prostate cancer. From the current evidence, patients should be fully informed of the risk of prostate cancer before vasectomy.
Article
Few genetic risk factors have been demonstrated to be specifically associated with aggressive prostate cancer (PrCa). Here, we report a case‐case study of PrCa comparing the prevalence of germline pathogenic/likely pathogenic (P/LP) genetic variants in 787 men with aggressive disease and 769 with non‐aggressive disease. Overall, we observed P/LP variants in 11.4% of men with aggressive PrCa and 9.8% of men with non‐aggressive PrCa (two‐tailed Fisher’s exact tests, P = 0.28). The proportion of BRCA2 and ATM P/LP variant carriers in men with aggressive PrCa exceeded that observed in men with non‐aggressive PrCa; 18/787 carriers (2.3%) and 4/769 carriers (0.5%), P = 0.004, and 14/787 carriers (0.02%) and 5/769 carriers (0.01%), P = 0.06, respectively. Our findings contribute to the extensive international effort to interpret the genetic variation identified in genes included on gene‐panel tests, for which there is currently an insufficient evidence‐base for clinical translation in the context of PrCa risk.
Article
The opportunity to prevent, to improve their prognosis, or even to cure uro-oncological diseases by modifying the lifestyle habits is a very modern topical subject and represents a great and fascinating challenge for the future. A PubMed and Web of Science databases search has been performed to review the published knowledge on most important lifestyle habits, such as smoking, physical activity, nutrition, sexual activity, and personal hygiene, highlighting modifiable factors influencing development and progression of urological cancers. Cigarette smoking has been historically established as risk factors for urothelial cancer, and an association with risk of renal cell carcinoma and worse prognosis of prostate cancer has been sufficiently demonstrated. Poor genital hygiene is a recognized risk factor for penile cancer. Furthermore, a convincing evidence has been found on the association between physical activity and both risk and prognosis of bladder and prostate cancer. Obesity is strongly associated with increased risk of developing lethal prostate cancer. An unequivocal evidence of a direct relationship between most of the other lifestyle habits and development of the uro-oncological diseases has not been found.
Article
Introduction: The role of sexual activity (SA) on prostate cancer (PCa) risk is still controversial. Aim: To determine the associations among number of female sexual partners, age at first intercourse, ejaculation frequency (EF), and the risk of PCa. Methods: A systematic literature search on MEDLINE, Cochrane Central Register of Controlled Trials, and Web of Science based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted to identify the relevant studies published before April 2018. We calculated the summary odds ratio (OR) and 95% CI to determine the association between SA and PCa risk. A 2-stage dose-response meta-analysis was performed to explore the trend from the correlated log OR estimates. Main outcome measures: Outcome measures included characteristics of included studies, associations among number of female sexual partners, age at first intercourse, as well as EF and PCa risk. Results: A total of 21 case-control studies and 1 cohort study with 55,490 participants (14,976 patients and 40,514 controls) were included in this meta-analysis. Linear and significant dose-response associations were found among number of female sexual partner as well as age at first intercourse and PCa risk, an increment of 10 female sexual partners associated with a 1.10-fold increase of PCa risk (OR 1.10, 95% CI 1.01-1.21), and the risk of PCa was decreased by 4% for every 5-year delay in age at first intercourse (OR 0.96, 95% CI 0.92-0.99). Although no linear association was observed between EF and the risk of PCa, moderate EF (2-4 times per week) was significantly associated with a lower risk of PCa (OR 0.91, 95% CI 0.87-0.96). Clinical implications: Modification of SA factors would appear to be a useful low-risk approach to decreasing the risk of PCa. Strengths & limitations: This is the first dose-response meta-analysis performed to describe the association between SA and PCa risk. However, the direction of causality between SA and risk of PCa should be interpreted with caution because most included studies used case-control design. Conclusion: Meta-analysis of the included studies indicated that men with fewer sexual partner numbers, older age at first intercourse, and moderate frequent ejaculation were associated with a significantly decreased risk of PCa. Z Jian Z, Ye D, Chen Y, et al. Sexual Activity and Risk of Prostate Cancer: A Dose-Response Meta-Analysis. J Sex Med 2018;XX:XXX-XXX.
Article
Full-text available
Introduction: The role of testosterone supplementation (TS) as a possible treatment for male sexual dysfunction remains questionable. The aim of the present study is to meta-analyse data evaluating the effects of TS on male sexual function and its therapeutic synergism with the use of phosphodiesterase type 5 (PDE5i). Methods: An extensive Medline Embase and Cochrane search was performed including the following words: ‘testosterone’, ‘erectile dysfunction’. All randomized controlled trials (RCTs) comparing the effect of TS vs placebo on sexual function or the effect of TS as add on to PDE5ì s on sexual function were included. Data extraction was performed independently by two of the authors (A.M.I, G.C), and conflicts resolved by the third investigator (M.M). Results.: Out of 1702 retrieved articles, 41 were included in the study. In particular, 29 compared TS vs placebo, whereas 12 trials evaluated the effect of TS as add on to PDE5ìs. TS is able to significantly ameliorate erections and to improve other aspects of male sexual response in hypogonadal patients. However, the presence of publication bias was detected. After applying Duval and Tweedie ‘trim and fill’ method, the positive effect of TS on erectile function and libido components retained significance only in RCTs partially or completed supported from pharmaceutical companies (CI (0.04–0.53) and (0.12;0.52) respectively). In addition, we also report that TS could be associated with an improvement in PDE5i outcome. These results were not confirmed when placebo-controlled studies were selectively analysed. The majority of them, however, included mixed eugonadal/hypogonadal subjects. Conclusions: TS plays positive effects on male sexual function in hypogonadal subjects. The apparent difference between industry-supported and independent studies could depend on trial design more than on publication bias. New RCTs exploring the effect of TS in selected cases of PDE5i failure who persistently retain low T levels are advisable.
Article
Full-text available
Abstract In November, 2014, 65 prostate cancer pathology experts, along with 17 clinicians including urologists, radiation oncologists, and medical oncologists from 19 different countries gathered in a consensus conference to update the grading of prostate cancer, last revised in 2005. The major conclusions were: (1) Cribriform glands should be assigned a Gleason pattern 4, regardless of morphology; (2) Glomeruloid glands should be assigned a Gleason pattern 4, regardless of morphology; (3) Grading of mucinous carcinoma of the prostate should be based on its underlying growth pattern rather than grading them all as pattern 4; and (4) Intraductal carcinoma of the prostate without invasive carcinoma should not be assigned a Gleason grade and a comment as to its invariable association with aggressive prostate cancer should be made. Regarding morphologies of Gleason patterns, there was clear consensus on: (1) Gleason pattern 4 includes cribriform, fused, and poorly formed glands; (2) The term hypernephromatoid cancer should not be used; (3) For a diagnosis of Gleason pattern 4, it needs to be seen at 10x lens magnification; (4) Occasional/seemingly poorly formed or fused glands between well-formed glands is insufficient for a diagnosis of pattern 4; (5) In cases with borderline morphology between Gleason pattern 3 and pattern 4 and crush artifacts, the lower grade should be favored; (6) Branched glands are allowed in Gleason pattern 3; (7) Small solid cylinders represent Gleason pattern 5; (8) Solid medium to large nests with rosette-like spaces should be considered to represent Gleason pattern 5; and (9) Presence of unequivocal comedonecrosis, even if focal is indicative of Gleason pattern 5. It was recognized by both pathologists and clinicians that despite the above changes, there were deficiencies with the Gleason system. The Gleason grading system ranges from 2 to 10, yet 6 is the lowest score currently assigned. When patients are told that they have a Gleason score 6 out of 10, it implies that their prognosis is intermediate and contributes to their fear of having a more aggressive cancer. Also, in the literature and for therapeutic purposes, various scores have been incorrectly grouped together with the assumption that they have a similar prognosis. For example, many classification systems consider Gleason score 7 as a single score without distinguishing 3+4 versus 4+3, despite studies showing significantly worse prognosis for the latter. The basis for a new grading system was proposed in 2013 by one of the authors (J.I.E.) based on data from Johns Hopkins Hospital resulting in 5 prognostically distinct Grade Groups. This new system was validated in a multi-institutional study of over 20,000 radical prostatectomy specimens, over 16,000 needle biopsy specimens, and over 5,000 biopsies followed by radiation therapy. There was broad (90%) consensus for the adoption of this new prostate cancer Grading system in the 2014 consensus conference based on: (1) the new classification provided more accurate stratification of tumors than the current system; (2) the classification simplified the number of grading categories from Gleason scores 2 to 10, with even more permutations based on different pattern combinations, to Grade Groups 1 to 5; (3) the lowest grade is 1 not 6 as in Gleason, with the potential to reduce overtreatment of indolent cancer; and (4) the current modified Gleason grading, which forms the basis for the new grade groups, bears little resemblance to the original Gleason system. The new grades would, for the foreseeable future, be used in conjunction with the Gleason system [ie. Gleason score 3+3=6 (Grade Group 1)]. The new grading system and the terminology Grade Groups 1-5 have also been accepted by the World Health Organization for the 2016 edition of Pathology and Genetics: Tumours of the Urinary System and Male Genital Organs. PMID: 26492179 DOI: 10.1097/PAS.0000000000000530 [Indexed for MEDLINE]
Article
Full-text available
Importance Leisure-time physical activity has been associated with lower risk of heart-disease and all-cause mortality, but its association with risk of cancer is not well understood. Objective To determine the association of leisure-time physical activity with incidence of common types of cancer and whether associations vary by body size and/or smoking. Design, Setting, and Participants We pooled data from 12 prospective US and European cohorts with self-reported physical activity (baseline 1987-2004). We used multivariable Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals for associations of leisure-time physical activity with incidence of 26 types of cancer. Leisure-time physical activity levels were modeled as cohort-specific percentiles on a continuous basis and cohort-specific results were synthesized by random-effects meta-analysis. Hazard ratios for high vs low levels of activity are based on a comparison of risk at the 90th vs 10th percentiles of activity. The data analysis was performed from January 1, 2014, to June 1, 2015. Exposures Leisure-time physical activity of a moderate to vigorous intensity. Main Outcomes and Measures Incident cancer during follow-up. Results A total of 1.44 million participants (median [range] age, 59 [19-98] years; 57% female) and 186 932 cancers were included. High vs low levels of leisure-time physical activity were associated with lower risks of 13 cancers: esophageal adenocarcinoma (HR 0.58, 95% CI 0.37-0.89), liver (HR 0.73, 95% CI 0.55-0.98), lung (HR 0.74, 95% CI 0.71-0.77), kidney (HR 0.77, 95% CI 0.70-0.85), gastric cardia (HR 0.78, 95% CI 0.64-0.95), endometrial (HR 0.79, 95% CI 0.68-0.92), myeloid leukemia (HR 0.80, 95% CI 0.70-0.92), myeloma (HR 0.83, 95% CI 0.72-0.95), colon (HR 0.84, 95% CI 0.77-0.91), head and neck (HR 0.85, 95% CI 0.78-0.93), rectal (HR 0.87, 95% CI 0.80-0.95), bladder (HR 0.87, 95% CI 0.82-0.92), and breast (HR 0.90, 95% CI 0.87-0.93). Body mass index adjustment modestly attenuated associations for several cancers, but 10 of 13 inverse associations remained statistically significant after this adjustment. Leisure-time physical activity was associated with higher risks of malignant melanoma (HR 1.27, 95% CI 1.16-1.40) and prostate cancer (HR 1.05, 95% CI 1.03-1.08). Associations were generally similar between overweight/obese and normal-weight individuals. Smoking status modified the association for lung cancer but not other smoking-related cancers. Conclusions and Relevance Leisure-time physical activity was associated with lower risks of many cancer types. Health care professionals counseling inactive adults should emphasize that most of these associations were evident regardless of body size or smoking history, supporting broad generalizability of findings.
Article
Full-text available
Background: Evidence suggests that ejaculation frequency may be inversely related to the risk of prostate cancer (PCa), a disease for which few modifiable risk factors have been identified. Objective: To incorporate an additional 10 yr of follow-up into an original analysis and to comprehensively evaluate the association between ejaculation frequency and PCa, accounting for screening, clinically relevant disease subgroups, and the impact of mortality from other causes. Design, setting, and participants: A prospective cohort study of participants in the Health Professionals Follow-up Study utilizing self-reported data on average monthly ejaculation frequency. The study includes 31925 men who answered questions on ejaculation frequency on a 1992 questionnaire and followed through to 2010. The average monthly ejaculation frequency was assessed at three time points: age 20-29 yr, age 40-49 yr, and the year before questionnaire distribution. Outcome measurements and statistical analysis: Incidence of total PCa and clinically relevant disease subgroups. Cox models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results and limitations: During 480831 person-years, 3839 men were diagnosed with PCa. Ejaculation frequency at age 40-49 yr was positively associated with age-standardized body mass index, physical activity, divorce, history of sexually transmitted infections, and consumption of total calories and alcohol. Prostate-specific antigen (PSA) test utilization by 2008, number of PSA tests, and frequency of prostate biopsy were similar across frequency categories. In multivariable analyses, the hazard ratio for PCa incidence for ≥21 compared to 4-7 ejaculations per month was 0.81 (95% confidence interval [CI] 0.72-0.92; p<0.0001 for trend) for frequency at age 20-29 yr and 0.78 (95% CI 0.69-0.89; p<0.0001 for trend) for frequency at age 40-49 yr. Associations were driven by low-risk disease, were similar when restricted to a PSA-screened cohort, and were unlikely to be explained by competing causes of death. Conclusions: These findings provide additional evidence of a beneficial role of more frequent ejaculation throughout adult life in the etiology of PCa, particularly for low-risk disease. Patient summary: We evaluated whether ejaculation frequency throughout adulthood is related to prostate cancer risk in a large US-based study. We found that men reporting higher compared to lower ejaculatory frequency in adulthood were less likely to be subsequently diagnosed with prostate cancer.
Article
Full-text available
In November, 2014, 65 prostate cancer pathology experts, along with 17 clinicians including urologists, radiation oncologists, and medical oncologists from 19 different countries gathered in a consensus conference to update the grading of prostate cancer, last revised in 2005. The major conclusions were: (1) Cribriform glands should be assigned a Gleason pattern 4, regardless of morphology; (2) Glomeruloid glands should be assigned a Gleason pattern 4, regardless of morphology; (3) Grading of mucinous carcinoma of the prostate should be based on its underlying growth pattern rather than grading them all as pattern 4; and (4) Intraductal carcinoma of the prostate without invasive carcinoma should not be assigned a Gleason grade and a comment as to its invariable association with aggressive prostate cancer should be made. Regarding morphologies of Gleason patterns, there was clear consensus on: (1) Gleason pattern 4 includes cribriform, fused, and poorly formed glands; (2) The term hypernephromatoid cancer should not be used; (3) For a diagnosis of Gleason pattern 4, it needs to be seen at 10x lens magnification; (4) Occasional/seemingly poorly formed or fused glands between well-formed glands is insufficient for a diagnosis of pattern 4; (5) In cases with borderline morphology between Gleason pattern 3 and pattern 4 and crush artifacts, the lower grade should be favored; (6) Branched glands are allowed in Gleason pattern 3; (7) Small solid cylinders represent Gleason pattern 5; (8) Solid medium to large nests with rosette-like spaces should be considered to represent Gleason pattern 5; and (9) Presence of unequivocal comedonecrosis, even if focal is indicative of Gleason pattern 5. It was recognized by both pathologists and clinicians that despite the above changes, there were deficiencies with the Gleason system. The Gleason grading system ranges from 2 to 10, yet 6 is the lowest score currently assigned. When patients are told that they have a Gleason score 6 out of 10, it implies that their prognosis is intermediate and contributes to their fear of having a more aggressive cancer. Also, in the literature and for therapeutic purposes, various scores have been incorrectly grouped together with the assumption that they have a similar prognosis. For example, many classification systems consider Gleason score 7 as a single score without distinguishing 3+4 versus 4+3, despite studies showing significantly worse prognosis for the latter. The basis for a new grading system was proposed in 2013 by one of the authors (J.I.E.) based on data from Johns Hopkins Hospital resulting in 5 prognostically distinct Grade Groups. This new system was validated in a multi-institutional study of over 20,000 radical prostatectomy specimens, over 16,000 needle biopsy specimens, and over 5,000 biopsies followed by radiation therapy. There was broad (90%) consensus for the adoption of this new prostate cancer Grading system in the 2014 consensus conference based on: (1) the new classification provided more accurate stratification of tumors than the current system; (2) the classification simplified the number of grading categories from Gleason scores 2 to 10, with even more permutations based on different pattern combinations, to Grade Groups 1 to 5; (3) the lowest grade is 1 not 6 as in Gleason, with the potential to reduce overtreatment of indolent cancer; and (4) the current modified Gleason grading, which forms the basis for the new grade groups, bears little resemblance to the original Gleason system. The new grades would, for the foreseeable future, be used in conjunction with the Gleason system [ie. Gleason score 3+3=6 (Grade Group 1)]. The new grading system and the terminology Grade Groups 1-5 have also been accepted by the World Health Organization for the 2016 edition of Pathology and Genetics: Tumours of the Urinary System and Male Genital Organs.
Article
Full-text available
A great variety of studies on preoperative serum testosterone as a predictor of progression of prostate cancer have been reported recently. The purpose of this study was to investigate the relationship of preoperative serum testosterone levels in patients who underwent radical prostatectomy with prognostic factors. Clinical data were collected from 60 patients who underwent radical prostatectomy. The 60 cases were divided into 2 groups according to their preoperative serum testosterone levels: group 1 (n=21), <3 ng/ml; group 2 (n=39), ≥3 ng/ml. The groups were compared according to prog-ression factors. Multivariate logistic regression analysis was performed to determine the correlation between biochemical recurrence and each variable. The incidence of extraprostatic invasions was significantly higher in group 1 with 13 cases in group 1 (61.9%) and 11 cases in group 2 (28.2%) (p=0.011). The incidence of biochemical recurrence was also significantly higher in group 1 with 5 cases in group 1 (23.8%) and 2 cases in group 2 (5.1%) (p=0.032). A low serum testosterone level (≤3 ng/ml) was associated with an increased risk of biochemical recurrence (odds ratio [OR], 13.64; 95% confidence interval [CI], 1.66 to 2.43; p=0.015) and an increased risk of extraprostatic invasions (OR, 4.96; 95% CI, 1.41 to 17.38; p=0.012). The incidence rates of extraprostatic invasions and biochemical recurrence were significantly higher in the group with preoperative average serum testosterone of less than 3 ng/ml. Therefore, these results suggest that preoperative average serum testosterone will be useful in predicting postoperative prostate cancer progression.
Article
Full-text available
The association between aging-related testosterone deficiency and late-onset hypogonadism in men remains a controversial concept. We sought evidence-based criteria for identifying late-onset hypogonadism in the general population on the basis of an association between symptoms and a low testosterone level. We surveyed a random population sample of 3369 men between the ages of 40 and 79 years at eight European centers. Using questionnaires, we collected data with regard to the subjects' general, sexual, physical, and psychological health. Levels of total testosterone were measured in morning blood samples by mass spectrometry, and free testosterone levels were calculated with the use of Vermeulen's formula. Data were randomly split into separate training and validation sets for confirmatory analyses. In the training set, symptoms of poor morning erection, low sexual desire, erectile dysfunction, inability to perform vigorous activity, depression, and fatigue were significantly related to the testosterone level. Increased probabilities of the three sexual symptoms and limited physical vigor were discernible with decreased testosterone levels (ranges, 8.0 to 13.0 nmol per liter [2.3 to 3.7 ng per milliliter] for total testosterone and 160 to 280 pmol per liter [46 to 81 pg per milliliter] for free testosterone). However, only the three sexual symptoms had a syndromic association with decreased testosterone levels. An inverse relationship between an increasing number of sexual symptoms and a decreasing testosterone level was observed. These relationships were independently confirmed in the validation set, in which the strengths of the association between symptoms and low testosterone levels determined the minimum criteria necessary to identify late-onset hypogonadism. Late-onset hypogonadism can be defined by the presence of at least three sexual symptoms associated with a total testosterone level of less than 11 nmol per liter (3.2 ng per milliliter) and a free testosterone level of less than 220 pmol per liter (64 pg per milliliter).
Article
Full-text available
Series editors J M Stephenson, A Babiker The study of sexual behaviour lies at the heart of understanding the transmission dynamics of sexually transmitted infections (STIs). Academic investigation into sexual behaviour dates back to the 18th century and, over time, has employed a variety of approaches including the medical and psychiatric investigation of sexual disorders, anthropological investigations, and survey research based largely on volunteer samples. More recent studies, driven largely by the public health response to HIV/AIDS, have focused on large scale probability sample survey research.1–5 Key areas of inquiry have shifted towards describing population patterns of risk behaviours for STI/HIV transmission, understanding how epidemics of STIs are generated, and informing disease control strategies. Sexual behaviour is a largely private activity, subject to varying degrees of social, cultural, religious, moral and legal norms and constraints. A key challenge for all sex survey research is to generate unbiased and precise measures of individual and population behaviour patterns. Methods are needed to minimise measurement error which may be introduced by participation bias, recall and comprehension problems, and respondents' willingness to report sensitive and sometimes socially censured attitudes or behaviours.6, 7 This paper briefly considers the role of different types of study in understanding STI epidemiology. It then focuses on potential sources of measurement error in survey research and strategies for assessing and limiting them.Sex Transm Inf 2001;77:84–92 The type of study chosen will depend on the purpose of the investigation. However, studies generally fall into four main groups: general population surveys, studies on population subgroups, partner and network studies, ethnographic and qualitative studies. ### GENERAL POPULATION PROBABILITY SAMPLE SURVEYS Cross sectional population surveys aim to describe the overall distribution of behaviours in populations. By using probability sampling techniques and maximising response rates, large scale behavioural surveys can provide robust estimates of the prevalence …
Article
Full-text available
Psychologists have worried about the distortions introduced into standardized personality measures by social desirability bias. Survey researchers have had similar concerns about the accuracy of survey reports about such topics as illicit drug use, abortion, and sexual behavior. The article reviews the research done by survey methodologists on reporting errors in surveys on sensitive topics, noting parallels and differences from the psychological literature on social desirability. The findings from the survey studies suggest that misreporting about sensitive topics is quite common and that it is largely situational. The extent of misreporting depends on whether the respondent has anything embarrassing to report and on design features of the survey. The survey evidence also indicates that misreporting on sensitive topics is a more or less motivated process in which respondents edit the information they report to avoid embarrassing themselves in the presence of an interviewer or to avoid repercussions from third parties.
Article
A population-based case-control study of prostate cancer was performed in King County, Washington, in White men and Black men aged 40-64 years, between 1993 and 1996. Incident prostate cancer cases (n = 753) were identified from the Seattle-Puget Sound Surveillance, Epidemiology, and End Results (SEER) cancer registry. Controls (n = 703) were identified through random digit dialing and were frequency matched to cases on age. Sexual behavior, medical history, and other potential prostate cancer risk factors were ascertained through an in-person interview. There was no relation between sexual orientation and prostate cancer, although the number of men who had sex with men was small. Risk estimates increased directly with the lifetime number of female sexual partners (trend p < 0.001) but not with male partners (trend p = 0.62). Risk also increased with decreasing age at first intercourse, but this effect disappeared after adjusting for the number of female partners. Prior infection with gonorrhea was positively associated with risk (odds ratio = 1.50; 95% confidence interval: 1.0, 2.2), but no effect was seen among men with other sexually transmitted diseases. No relation between lifetime frequency of sexual intercourse and risk of prostate cancer was apparent. These findings are consistent with previous studies that support an infectious etiology for prostate cancer.
Article
Background: The controversy surrounding the relationship between testosterone and prostate cancer has existed for decades. The literature surrounding this topic is confusing and at times contradictory. There is no level-one quality evidence that confirms or refutes the relationship between either high or low serum testosterone levels and the subsequent development of prostate cancer. This commentary aims to review the issues involved and to provide an interpretation as to the causes of the confusion and to provide a framework for ongoing discussion and investigation. Materials and methods: A Medline and PubMed search was conducted using search terms: testosterone levels and prostate cancer to identify pertinent literature. Results: There is no consistent evidence that a single testosterone level is predictive of prostate cancer risk. Conclusion: The development of prostate cancer is a complex biologic process potentially involving genetics,dietary, life style and hormonal factors. Serum testosterone levels do not accurately reflect the internal prostatic milieu. Finally, if testosterone levels are to be considered in the etiology of prostate cancer they should be measured and interpreted on a chronic basis with multiple measurements over a period of years.
Article
Epidemiological investigations may allow conclusions on the etiology of prostate cancer. Such data from autopsy studies and morbidity as well as mortality statistics are based on local or national cancer registries and informations obtained from death certificates. Clear cut evidence of certain environmental factors to be involved in prostate cancer development derives from the situation in Japan: (1) high incidence of latent carcinoma despite a 10-fold lower morbidity of manifest carcinoma compared to the western hemisphere; (2) increased grade of malignancy of latent carcinoma and approximating morbidity and mortality rates to the population of the country of immigration. A comparable situation is seen in the Jewish population. In Europe an absolute increase of morbidity is encountered: Cancer Registries of Birmingham, Hamburg, Sweden, Halle (DDR). According to the UICC following incidence rates can be calculated n per 100,000 population per year): USA - 33.9; Sweden - 26.5; England - 17.4; GFR - 16.5; Japanese immigrants - 12.6; Japan - 3.8, China - 0.9. German mortality data (Cancer Atlas of the GFR), which are based on death certificates, show a steady increase between 1955 and 1975 without conclusive differences for the various 'Bundeslander'. On a world-wide basis neither studies on endocrinology nor on the socioeconomic status or sexual life, infectious as well as genetic factors have provided a valuable clue for the etiology of prostatic carcinoma.
Article
Controversy exists regarding the propensity of hypogonadism and metabolic disorders to promote the development of high-risk prostate cancer (PCa). Our aim was to prospectively test whether preoperative circulating testosterone levels, obesity, and metabolic syndrome (MetS) were correlated with aggressive pathological features after radical prostatectomy (RP). Overall, 354 patients undergoing robot-assisted RP at our academic institution, between 2010 and 2013, to treat clinically localized PCa were included in this prospective study. Pelvic lymphadenectomy was performed in 116 (32.8%) patients and confirmed the absence of nodal metastases in all of them. Cardiovascular risk factors and body-mass index (BMI) were used to define MetS and obesity, respectively. Total testosterone (TT) levels were assessed using an immunoassay method, whereas bioavailable testosterone (BT) and free testosterone (FT) levels were estimated using Vermeulen׳s formula. Multivariate logistic regression analyses assessed independent predictors for postoperative aggressive pathological features (i.e., a pathological Gleason score [GS]≥7, extracapsular extension [ECE], seminal vesicle invasion [SVI], and positive surgical margins [PSM]) and GS upgrading. Low TT, BT, and FT levels were found in 54 (15.2%), 70 (19.8%), and 62 (17.5%) patients, respectively. Median BMI was 26.3kg/m(2) (range: 17.4-43.9), and prevalence of MetS was 18.9%. Significantly higher rates of pathological GS≥7 were observed in groups with a low TT level (46.3% vs. 33.3%; P = 0.01), low BT level (44.3% vs. 33.1%; P<0.001), and low FT level (46.8% vs. 32.9%; P = 0.001). Multivariate analyses demonstrated that only low BT and FT levels were independent predictors of pathological GS≥7 (odds ratio [OR] = 1.76; P<0.001 and OR = 1.39; P<0.001, respectively) and GS upgrading (OR = 2.82; P<0.001 and OR = 1.71; P<0.001, respectively), but there was no significant correlation between low circulating testosterone levels and ECE, SVI, or PSM. Furthermore, BMI (OR = 1.28; P = 0.04) and MetS (OR = 1.19; P = 0.01) were only correlated with PSM. Hypogonadism, obesity, and MetS were not independent predictors of pathological GS ≥7, ECE, or SVI after RP. Our data suggest that only low BT and FT levels, which might logically result in an active androgen-depleted environment, were linked with high-grade PCa. Copyright © 2014 Elsevier Inc. All rights reserved.
Article
Background: The etiology of prostate cancer (PCa) is poorly understood. Sexual activity and sexually transmitted infections (STIs) are among factors under scrutiny, with controversial findings to date. Methods: We examined the association between the number and gender of sexual partners, STIs and PCa risk in the context of PROtEuS, a population-based case-control study set amongst the mainly French-speaking population in Montreal, Canada. The study included 1590 histologically-confirmed PCa cases diagnosed in a Montreal French hospital between 2005 and 2009, and 1618 population controls ascertained from the French electoral list, Montreal residents, frequency-matched to cases by age. In-person interviews elicited information on sociodemographic, lifestyle and environmental factors. Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) between sexually related factors and PCa risk, adjusting for age, ancestry, family history of PCa, and PCa screening history. Results: Subjects with more than 20 sexual partners in their lifetime had a decreased risk of PCa (OR 0.78, 95% CI 0.61-1.00) as did subjects who specifically had more than 20 female sexual partners (OR 0.72, 95% CI 0.56-0.94). By contrast, having had several male sexual partners appeared to confer some excess in risk of PCa. No association emerged for history of STIs and PCa but STIs prevalence was low. Conclusion: Our findings are in support of a role for the number of sexual partners in PCa development. The gender of sexual partners should be taken into account in future studies investigating this association.
Article
Introduction: The role of testosterone supplementation (TS) as a treatment for male sexual dysfunction remains questionable. Aim: The aim of this study was to attempt a meta-analysis on the effect of TS on male sexual function and its synergism with the use of phosphodiesterase type 5 inhibitor (PDE5i). Methods: An extensive Medline, Embase, and Cochrane search was performed. Main outcome measures: All randomized controlled trials (RCTs) comparing the effect of TS vs. placebo or the effect of TS as add on to PDE5is on sexual function were included. Data extraction was performed independently by two of the authors (A. M. Isidori and G. Corona), and conflicts resolved by the third investigator (M. Maggi). Results: Out of 1,702 retrieved articles, 41 were included in the study. In particular, 29 compared TS vs. placebo, whereas 12 trials evaluated the effect of TS as add on to PDE5is. TS is able to significantly ameliorate erectile function and to improve other aspects of male sexual response in hypogonadal patients. However, the presence of possible publication bias was detected. After applying "trim and fill" method, the positive effect of TS on erectile function and libido components retained significance only in RCTs partially or completely supported by pharmaceutical companies (confidence interval [0.04-0.53] and [0.12; 0.52], respectively). In addition, we also report that TS could be associated with an improvement in PDE5i outcome. These results were not confirmed in placebo-controlled studies. The majority of studies, however, included mixed eugonadal/hypogonadal subjects, thus imparting uncertainty to the statistical analyses. Conclusions: TS plays positive effects on male sexual function in hypogonadal subjects. The role of TS is uncertain in men who are not clearly hypogonadal. The apparent difference between industry-supported and independent studies could depend on trial design more than on publication bias. New RCTs exploring the effect of TS in selected cases of PDE5i failure that persistently retain low testosterone levels are advisable.
Article
Although prostate cancer (PCa) screening reduces the incidence of advanced disease and mortality, trade-offs include overdiagnosis and resultant overtreatment. To review primary data on PCa overdiagnosis and overtreatment. Electronic searches were conducted in Cochrane Central Register of Controlled Trials, PubMed, and Embase from inception to July 2013 for original articles on PCa overdiagnosis and overtreatment. Supplemental articles were identified through hand searches. The lead-time and excess-incidence approaches are the main ways used to estimate overdiagnosis in epidemiological studies, with estimates varying widely. The estimated number of PCa cases needed to be diagnosed to save a life has ranged from 48 down to 5 with increasing follow-up. In clinical studies, generally lower rates of overdiagnosis have been reported based on the frequency of low-grade minimal tumors at radical prostatectomy (1.7-46.8%). Autopsy studies have reported PCa in 18.5-38.5%, although not all are low grade or low volume. Factors influencing overdiagnosis include the study population, screening protocol, and background incidence, limiting generalizability between settings. Reported rates of overtreatment vary widely in the literature, although contemporary international studies suggest increasing use of conservative management. Epidemiological, clinical, and autopsy studies have been used to examine PCa overdiagnosis, with estimates ranging widely from 1.7% to 67%. Correspondingly, estimates of overtreatment vary widely based on patient features and may be declining internationally. Careful patient selection for screening and reducing overtreatment are important to preserve the benefits and reduce the downstream harms of prostate-specific antigen testing. Because all of these estimates are extremely population and context specific, this must be considered when using these data to inform policy. Screening reduces spread and death from prostate cancer (PCa) but overdiagnoses some low-risk tumors that may not have caused harm. Because treatment has potential side effects, it is critical that not all patients with PCa receive aggressive treatment.
Article
Study Type – Prognosis (prospective cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Previous data from clinically localized prostate cancer (PCa) series treated with radical prostatectomy (RP) have suggested that low preoperative serum total testosterone level is associated with more aggressive PCa; however, the definition of low preoperative total testosterone level varied among these studies (from 220 ng/dL to 387 ng/dL). Moreover, no relevant data exist in the literature regarding ethnic Chinese patients. The study shows that the most widely used threshold for low pretreatment total testosterone level (total testosterone < 300 ng/dL) is not appropriate for ethnic Chinese patients, because it could not distinguish patients with more aggressive PCa from those with less aggressive disease. Setting the threshold at the level of total testosterone < 250 ng/dL works better, because pretreatment total testosterone < 250 ng/dL is associated with a significantly higher incidence of Gleason score 8–10 disease in RP specimens.
Article
OBJECTIVE To assess whether prostate cancer might be related to hormone levels and, by inference, to differences in sexual activity.PATIENTS, SUBJECTS AND METHODS In a case-control study of men with prostate cancer aged < 70 years at diagnosis and age-matched control subjects, information was collected on two aspects of sexual activity; the number of sexual partners and the frequency of total ejaculations during the third to fifth decades of life.RESULTSThere was no association of prostate cancer with the number of sexual partners or with the maximum number of ejaculations in 24 h. There was a negative trend (P < 0.01) for the association between risk and number of ejaculations in the third decade, independent of those in the fourth or fifth. Men who averaged five or more ejaculations weekly in their 20s had an odds ratio (95% confidence interval) of 0.66 (0.49–0.87) compared with those who ejaculated less often.CONCLUSIONS The null association with the number of sexual partners argues against infection as a cause of prostate cancer in this population. Ejaculatory frequency, especially in early adult life, is negatively associated with the risk of prostate cancer, and thus the molecular biological consequences of suppressed or diminished ejaculation are worthy of further research.
Article
Data on testosterone levels of patients with prostate cancer of different grade and stage are inconsistent. We retrospectively investigated serum total testosterone of a radical prostatectomy cohort to further shed light on this problem. The preoperative level of serum total testosterone of 217 patients (mean age: 65±5.8 years) undergoing radical prostatectomy between 1989 and 2002 was analyzed for possible associations with Gleason score (≤6 vs. <7 vs. 8-10) and tumor stage (pT2 vs. pT3 vs. N+) with adjustment for age, diabetes and obesity. Patients exhibiting prostate-specific antigen (PSA) levels of >10 ng/ml and biopsy Gleason scores of ≥7 were submitted to standard lymphadenectomy. The multivariate model revealed a significant effect of body mass index (BMI) (p=0.0003) and diabetes (p=0.002) on testosterone levels. Significantly lower testosterone levels were recorded in patients with nodal metastases (p<0.0001) compared to patients with non metastatic disease. No significant associations between testosterone, Gleason score and stage were found in patients with non- metastatic disease. Testosterone levels prior to radical prostatectomy were lower in patients with nodal involvement.
Article
Introduction: Epidemiologic studies exploring sexuality across different cultures and geographic regions are scanty, particularly from the Middle East. The Global Online Sexuality Survey (GOSS) is an Internet-based survey investigating male and female sexual function. GOSS-Arabic-Males is the Arabic version targeting males in the Middle East, exploring prevalence rate of and factors affecting erectile dysfunction and its therapeutic trends, as well as premature ejaculation, attitudes toward genital size, and contraception. Aim: To explore epidemiologic aspects of male sexuality through an online survey. Main outcome measures: Prevalence rate of erectile dysfunction, its relationship to risk factors, and therapeutic trends. Methods: The online survey was randomly offered to Web surfers in the Middle East. Results: Eight hundred four subjects completed the survey. The overall prevalence of ED was 45.1%, strongly correlating with various risk factors studied, including age, diabetes, hypertension under treatment, depression, concerns over genital size, interpersonal distress, premature ejaculation, low libido, and subjective reports of penile deviation. Adjusted to the World Standard Population, the prevalence rate for ED was 47%. Phosphodiesterase (PDE) inhibitors gave a poor response among those with low libido and interpersonal distress, emphasizing the need for proper diagnosis and psychological counseling parallel to medical treatment. Furthermore, PDE inhibitors were stigmatized with unrealistic concerns that decreased their utility to a great extent. Conclusion: In the study population of Arab-speaking Internet users, prevalence of erectile dysfunction and effect of risk factors have proven similar to reports from different parts of the world, though not unanimously. Premature ejaculation, low desire, concerns over penile size, and penile curvature are factors to be considered in the evaluation of ED patients. PDE inhibitors are stigmatized with false beliefs that should be addressed through mass media and counseling if this population is to take full benefit from this therapeutic option.
Article
High sexual activity (SA) has been reported to reduce the risk of prostate cancer (PC). The role of sex hormones (SHs) in this regard remains controversial. To determine the impact of SA and SHs on PC development. In a multicentric hospital-based case-control study, 194 newly diagnosed PC patients along with 317 age-matched controls were studied. Sociodemographic and medical characteristics of participants were recorded. History of vasectomy and sexually transmitted infection (STI), marital status, age at first intercourse, premarital sex, and the current frequency of sexual intercourses per month (SPM) were evaluated. Total testosterone (TT), free testosterone (FT), estradiol (ES), sex hormone binding globulin, and albumin were also measured. Logistic regression model was used to identify independent risk factors for PC. (i) The association between SA, SHs, and the risk of PC; (ii) The correlation between SHs and SA; (iii) The interaction between SHs and SA and established risk factors for PC and erectile dysfunction in determining the risk of PC; and (iv) The correlation between SHs and SA in determining the risk of PC in different decades of life. Vasectomy, STI, and marital status did not differ significantly between two cohorts. Controls reported premarital sex more commonly than cases (P < 0.001). Cases had the first intercourse at older age (P = 0.03) and had less SPM (P < 0.001). TT, FT, and ES were higher in controls (P < 0.001). In multivariate analysis, TT, calculated FT, SPM >4, and age at time of marriage <24 were protective against PC. The protective effect of high SA and SHs increased as patients' age increased. High SA as well as TT and FT were protective against PC. Their protective role enhances by each decade of increasing age. The protective effect of high SA was independent from circulating levels of SHs.
Article
• To investigate the relationship between pretreatment testosterone levels and pathological specimen characteristics, by prospectively examining serum androgen concentrations in a well-studied cohort of patients who underwent radical prostatectomy (RP) for localized prostate cancer. • A total of 107 patients with clinically localized prostate cancer had an assay of total testosterone before laparoscopic RP at our institution. • The results were classified into two groups based on the total serum testosterone: group1, < 3 ng/mL; group 2, ≥ 3 ng/mL. • Student's t-test was used to compare continuous variables, and Fisher's exact test or the chi-squared test was used to compare categorical variables. • Survival curves were established using the Kaplan-Meier method and compared using the log-rank test. In all tests, P < 0.05 was considered to indicate statistical significance. • All patients had localized prostate cancer based on digital rectal examination (DRE) and preoperative magnetic resonance imaging (MRI). Groups 1 and 2 were similar in terms of age, body mass index, preoperative co-morbidities (cardiovascular and diabetes mellitus), clinical stage of prostate cancer and preoperative PSA levels. • In pathological specimens, low total testosterone (< 3 ng/mL) was an independent risk factor for high Gleason score (> 7) and for locally advanced pathological stage (pT3 and pT4). • Higher preoperative testosterone correlated with disease confined to the gland. • There was no association between serum testosterone levels and surgical margin status, on the one hand, and biochemical recurrence on the other. • Low serum testosterone appears to be predictive of aggressive disease (Gleason score >7 and extraprostatic disease, pathological stage > pT2) in patients who underwent RP for localized prostate cancer.
Article
In this paper, studies by a large series of independent investigators are reviewed with regard to the basic structure and function of the prostate in an attempt to examine their relationship to prostatic cancer etiology. These studies demonstrate that the functional activities of the prostate involve secretion, transport, and reabsorption of a variety of materials into and out of the glandular lumen and that these activities are directly related to the basic structural organization of the gland. These functional activities are constantly occurring in the prostate even under basal (ie, nonejaculating) conditions. Due to these functional activities, the prostatic fluid in the glandular lumen is a complex mixture of a variety of components derived, not only from the synthetic activity of the glandular epithelial cells of the gland itself, but also from the blood serum. The levels of these components are continuously modulated, not only by the frequency of active ejaculation, but also, under basal conditions by the continuous interaction with the glandular prostatic cells lining the acinar lumen and ducts. A concept is presented that the initiation and/or promotion of prostatic carcinogenesis may well involve the chronic modulation/interaction of the prostatic glandular cells with their lumenal fluid.
Article
A population-based case-control study was carried out among 981 men (479 black, 502 white) with pathologically confirmed prostate cancer and 1315 controls (594 black, 721 white). In-person interviews elicited information on sexual behaviour and other potential risk factors for prostate cancer. Blood was drawn for serologic studies in a subset of the cases (n = 276) and controls (n = 295). Prostate cancer risk was increased among men who reported a history of gonorrhoea or syphilis (odds ratio (OR) = 1.6; 95% confidence internal (CI) 1.2-2.1) or showed serological evidence of syphilis (MHA-TP) (OR = 1.8; 95% CI 1.0-3.5). Patterns of risk for gonorrhoea and syphilis were similar for blacks (OR = 1.7; 95% CI 1.2-2.2) and whites (OR = 1.6; 95% CI 0.8-3.2). Risks increased with increasing occurrences of gonorrhoea, rising to OR = 3.3 (95% CI 1.4-7.8) among subjects with three or more events (Ptrend = 0.0005). Frequent sexual encounters with prostitutes and failure to use condoms were also associated with increased risk. Syphilis, gonorrhoea, sex with prostitutes and unprotected sexual intercourse may be indicators of contact with a sexually transmissible factor that increases the risk of prostate cancer.
Article
Because more and more men are being diagnosed with prostate cancer worldwide, knowledge about and prevention of this disease is important. Epidemiological studies have provided some insight about the cause of prostate cancer in terms of diet and genetic factors. However, compared with other common cancers such as breast and lung cancer, the causes remain poorly understood. Several important issues could help in our understanding of this disease-the variation in incidence of prostate cancer between ethnic populations and the factors leading to familial clustering of the diseases.
Article
Corpora amylacea in the prostate are a frequent finding in benign acini, but are only rarely observed in adenocarcinoma. To determine the incidence and comparative histopathology of this finding, we prospectively reviewed all consecutive needle core biopsies (excluding consultations) received at Bostwick Laboratories between December 2001 and July 2003. Among 5130 cases of adenocarcinoma (34% of 15,279 total needle biopsy cases), we identified 19 (31 biopsy specimens) with corpora amylacea within cancerous acini (0.4% incidence). Patients ranged in age from 51 to 89 years (mean, 68 years). The corpora amylacea were located within cancers with Gleason pattern 3 (28 of 31 specimens), Gleason pattern 4 (one specimen), and Gleason pattern 5 (two specimens), and ranged from less than 0.1-0.3 mm in diameter. Coexistent eosinophilic proteinaceous debris was noted in all 31 specimens, luminal mucin in 19, crystalloids in 15, and collagenous micronodules in two specimens. Our results indicate that the incidence of corpora amylacea in adenocarcinoma is low, but the presence of such inclusions cannot be used to exclude malignancy.
Article
It has been reported that more aggressive prostate cancer (PC) can be associated with low serum testosterone levels. The relationship between serum androgens and PC is still not completely understood. In this study we examined the association of prognostic factors in men who underwent radical retropubic (RRP) prostatectomy with low or normal total testosterone. We retrospectively evaluated 64 consecutive patients with localized PC treated with RRP between July 2002 and November 2003. PC was diagnosed by transrectal ultrasonography guided biopsy performed for either a suspicious digital rectal examination or serum prostate specific antigen greater than 4.0 ng/ml. Gleason score was determined in prostatic biopsies. Pathological TNM staging (1997), capsular perforation, seminal vesicle involvement and surgical margin status were determined in all surgical specimens. The threshold for serum total testosterone was 270 ng/dl. In all analyses p <0.05 was considered statistically significant. There were no statistically significant differences among prostate specific antigen, Gleason score (biopsy or specimen), pathological stage, capsular perforation and seminal vesicle involvement. However, patients with low total testosterone had increased positive surgical margins (p = 0.026). Patients with low total testosterone more frequently present with positive surgical margins in RRP specimens. The true association between low testosterone and poor clinical outcome in the long term needs validation in large prospective studies.
Article
Epidemiologic studies have failed to support the hypothesis that circulating androgens are positively associated with prostate cancer risk and some recent studies have even suggested that high testosterone levels might be protective particularly against aggressive cancer. We tested this hypothesis by measuring total testosterone, androstanediol glucuronide, androstenedione, DHEA sulfate, estradiol, and sex hormone-binding globulin in plasma collected at baseline in a prospective cohort study of 17,049 men. We used a case-cohort design, including 524 cases diagnosed during a mean 8.7 years follow-up and a randomly sampled sub-cohort of 1,859 men. The association between each hormone level and prostate cancer risk was tested using Cox models adjusted for country of birth. The risk of prostate cancer was approximately 30% lower for a doubling of the concentration of estradiol but the evidence was weak (P(trend)=0.07). None of the other hormones was associated with overall prostate cancer (P(trend) >or= 0.3). None of the hormones was associated with nonaggressive prostate cancer (all P(trend) >or= 0.2). The hazard ratio [HR; 95% confidence interval (95% CI)] for aggressive cancer almost halved for a doubling of the concentration of testosterone (HR, 0.55; 95% CI, 0.32-0.95) and androstenedione (HR, 0.51; 95% CI, 0.31-0.83), and was 37% lower for a doubling of the concentration of DHEA sulfate (HR, 0.63; 95% CI, 0.46-0.87). Similar negative but nonsignificant linear trends in risk for aggressive cancer were obtained for free testosterone, estradiol, and sex hormone-binding globulin (P(trend)=0.06, 0.2, and 0.1, respectively). High levels of testosterone and adrenal androgens are thus associated with reduced risk of aggressive prostate cancer but not with nonaggressive disease.
Article
Black men are diagnosed with prostate cancer more often than white men, present with more advanced disease and have worse stage specific survival. Given the high risk of incidence and mortality in this population, determining potentially modifiable factors is important. Recent studies have suggested a link between chronic inflammation and development of prostate cancer. In concurrence, population based studies of white men have revealed an increased risk of prostate cancer with history of sexually transmitted diseases and prostatitis. We explored the chronic inflammation hypothesis of prostate cancer development among black men by examining sexual activity, sexually transmitted diseases and prostatitis in a population based study of 129 patients and 703 controls 40 to 79 years old. After adjusting for age, income, cigarette smoking, and history of digital rectal examination and prostate specific antigen tests in the last 5 years, we observed that a history of gonorrhea infection and prostatitis increased the odds of prostate cancer 1.78-fold (95% CI 1.13, 2.79) and 4.93-fold (95% CI 2.79, 8.74), respectively. Men reporting 25 or more sexual partners were 2.80 (95% CI 1.29, 6.09) times more likely to be diagnosed with cancer compared to men with 5 or fewer partners. Our findings support the significance of prior sexual practices, exposure to sexually transmitted microbial agents and history of prostatic infection in the natural history of prostate cancer in black men. Additional prospective research incorporating serological markers of infectious agents or predictive markers of chronic inflammation should serve to elucidate the possible causal pathway of recurring or persistent infection in the etiology of prostate cancer in black men.
Development, molecular biology, and physiology of the prostate
  • A E Ross
  • R Rodriguez
Ross AE, Rodriguez R. Development, molecular biology, and physiology of the prostate. In Wein AJ, Kavoussi LR, Partin AW, Peters CA, editors. Campbell-Walsh urology. Philadelphia, PA: Elsevier; 2016:[chapter 102].
Census of Population and Housing: SocioEconomic Indexes for Areas (SEIFA), Australia
  • Australian Bureau
  • Statistics
Australian Bureau of Statistics. Census of Population and Housing: SocioEconomic Indexes for Areas (SEIFA), Australia, 2011. http://www.abs. gov.au/ausstats/abs@.nsf/mf/2033.0.55.001; 2011 [accessed June 3, 2016].
  • N P Papa
N.P. Papa et al. / Urologic Oncology: Seminars and Original Investigations 35 (2017) 530.e7-530.e13 530.e13