Urologic Disease Significantly Impacted by Dietary, Social Habits

San Francisco, CA (UroToday.com) – Dietary and social habits can have significant impacts on urinary health, as evidenced by new studies being presented at the 2019 AUA Annual Meeting in Chicago. Four studies highlight the positive effects of heart-healthy diets on erectile function, the impact of marijuana smoking on urinary health and the impact of restrictive diets on testosterone production. These studies will be presented during a special session for media on May 4, 2019 at 9:00 a.m. Mayo Clinic urologist Dr. Tobias Kohler, chair of the AUA Public Media Committee, will moderate this session. 

Abstracts presented include: 

Publication # MP46-03 The Association Between Popular Diets and Serum Testosterone Among Men in the United States 

Low-fat diets have been shown to have a number of health benefits, but may have a negative impact on serum testosterone levels in men. This study, using data from the National Health and Nutrition Examination Survey (NHANES), examined the relationship between diets and serum testosterone levels. Among the 7,316 men identified for the study, 15.9 percent (1,160) were on a low-fat diet, 26.3 percent (1,924) were on a Mediterranean diet and 67.2 percent (4,920) were on a non-restrictive diet. 

Key findings include: 
  • Compared to men with non-restrictive diets, average testosterone was lower among men with low-fat and Mediterranean diets.
  • Men adhering to a low-fat diet were more likely to have a testosterone level under 300 ng/dl compared to those on non-restrictive diets. 
Publication # MP75-09 Marijuana Consumption Has A Direct Deleterious Effect On Spermatozoa By Increasing Intracellular Reactive Oxygen Species Levels 20 Times More Than Tobacco Smoking: Reasons For Concern On Widespread Use 
Marijuana and tobacco smoke have been shown to increase oxidative stress in cells, including reactive oxygen species (ROS), unstable molecules that build up at the cellular level. A build-up of ROS within cells can lead to DNA or RNA damage, or even cellular death. In this study of 622 men, researchers explored the potential association between marijuana and tobacco use in testicular and sperm function, as well as male infertility and hypogonadism. Subjects were divided into four groups: marijuana users (74), tobacco users (144), infertile (125) and fertile (279). 

Key findings include: 
  • Seminal ROS levels were higher in the marijuana group compared to tobacco and fertile groups. 
  • Marijuana users had worse overall semen parameters (including sperm concentration, sperm count, motility and morphology) than tobacco users. 
Publication # PD19-08 Marijuana, Alcohol, ED and Depression: Epidemiologic Correlations with BPH/LUTS 
Prostatic enlargement (benign prostatic hyperplasia, or BPH) may cause men to experience bothersome lower urinary tract symptoms (LUTS), such as nocturia, weak urine streams and urgency. In this review of 20,548 patients on medical treatment for BPH/LUTS, researchers identified several risk factors for LUTS: depression, hypertension, metabolic syndrome, erectile dysfunction, and also marijuana use. This is the first time marijuana use has been implicated as a risk factor for urination problems. 

Key findings include: 
  • Marijuana use and erectile dysfunction were associated with an increased risk of being on a LUTS medication.
  • On multivariate analysis, marijuana remained associated with this increased risk. 
  • Alcohol use was not associated with an increased risk of BPH/LUTS. 
Publication # PD28-07 Heart Healthy Diet and Erectile Dysfunction in the Health Professionals Follow-Up Study 
Heart-healthy lifestyle changes – such as smoking cessation and weight loss – are attractive, non-pharmacologic options in the treatment of erectile dysfunction (ED), but is unknown whether heart-healthy diets have an association with ED. Researchers conducted a prospective analysis of 26,246 men ages 40 to 75 in the Health Professionals Follow-Up Study, which included assessments on erectile function and dietary questionnaires (used to calculate Mediterranean Diet and Alternative Health Eating Index scores) to review whether dietary choices were related to risk of incident ED.Key findings include: 

Mediteranean Diet and Alternative Health Eating Index (AHEI) scores were associated with decreased risk of incident ED.
  • The inverse association between Mediterranean Diet and AHEI scores was strongest in men under age 60.
  • Higher intakes of legumes, fruit, vegetables, fish and long-chain fats were associated with a decreased risk of ED, and red and processed meats and trans fats were positively association with ED risk. 
“This is the first time we’ve seen a definitive connection between marijuana use and certain urologic conditions such as infertility and BPH/LUTS, and in the context of legalization of cannabis, more research is warranted,” Dr. Kohler said. “Most importantly, these studies further underscore the need for healthy lifestyles and an understanding of how what we put in our bodies affects how they function.” 
Abstracts: 

MP46-03  The Association Between Popular Diets and Serum Testosterone Among Men in the United States 
Richard Fantus, Joshua Halpern, Cecilia Chang, Mary Keeter, Nelson Bennett, Brian Helfand, Robert Brannigan 

Introduction: Millions of Americans each year trial new diets hoping to lose weight, gain strength or increase their energy level. While multiple studies have examined the benefits of low-fat and Mediterranean diets, the effects of these diet regimens on serum testosterone (T) are unknown. We hypothesized that men who restrict their dietary fat intake may be at increased risk for decreased serum T, a steroid hormone with cholesterol precursors. 

Methods: The National Health and Nutrition Examination Survey (NHANES) database was queried from 1999-2004 and 2011-2012. Men 18-80 years who completed the two-day dietary history and underwent serum T testing were included. Diets were categorized as low-fat (American Heart Association), Mediterranean (inclusive of low-fat), or non-restrictive. Multivariable modeling was used to determine the relationship between diet and serum T. 

Results:
Among 7316 men who met inclusion criteria, 1160 (15.9%) met criteria for a low-fat diet, 1924 (26.3%) a Mediterranean diet, and 4920 (67.2%) a non-restrictive diet. Mean serum T was 435.5 &[plusmn] 6.7 ng/dL, and 838 men (26.7%) had serum T < 300 ng/dl. Compared to men with non-restrictive diets, mean T was lower among men with low-fat (410.8&[plusmn]8.1 vs 443.5&[plusmn]7.3, p=0.005) and Mediterranean diets (412.9&[plusmn]9.1 vs 443.5&[plusmn]7.3, p=0.002). Multivariable analysis controlling for age, body mass index (BMI), activity level, diabetes, comorbidities, and prostate cancer showed men with non-restrictive diets had higher serum T compared to those adhering to low-fat (parameter estimate[PE] -57.2, 95% confidence interval [CI] -105.6 - -8.8, p<0.05) or Mediterranean diets (PE -26.2, 95% CI -61.9 - 9.6, p=0.15). Men adhering to a low-fat diet were more likely to have a T level <300 ng/dl compared to their non-restrictive counterparts (odds ratio [OR] 2.33, 95% confidence interval [CI] 0.77-7.034, p=0.13), which approached but did not reach statistical significance. 

Conclusions: In a nationally representative sample, men adhering to restrictive diets had lower serum T levels. This remained true even when controlling for common covariates such as comorbidities, age, BMI and activity levels. Future prospective research is required to both corroborate these findings and elucidate the mechanisms by which restrictive dieting may affect serum T. 

Funding: none 


MP75-09 
Marijuana Consumption Has A Direct Deleterious Effect On Spermatozoa By Increasing Intracellular Reactive Oxygen Species Levels 20 Times More Than Tobacco Smoking: Reasons For Concern On Widespread Use 
Jorge Hallak, Thiago Afonso Teixeira, Juliana Risso Pariz, Ivan Iori, Elaine Costa, Paulo Hilario Saldiva 

Introduction: Marijuana is the most consumed illicit drug in the world, with approximately 200 million users, considered by many as an inoffensive and relaxing habit, with &[Prime]real harm&[Prime] anecdotally aimed solely from cigarette smoking. The aim of study is to evaluate the effects of marijuana and tobacco use in sperm and testicular function and its relationship with hypogonadism and male infertility. 

Methods: Cohort study that engaged 18-59-year-old male subjects who came for an andrological evaluation and who self-reported use of marijuana and cigarette smoking. These subjects were paired by age and compared with three other groups: (a) fertile men (pre-vasectomy candidates with no risk factors for testicular dysfunction), (b) infertile men (&[ge]12 months trying pregnancy without success) and (c) group of men who reported use of tobacco smoking only. A complete semen analysis (World Health Organization criteria), testis volume (orchidometer and/or ultrasonography), biochemical markers of sperm function and functional tests, including: creatine - kinase activity, anti-sperm antibodies, reactive oxygen species (ROS), DNA fragmentation (SCSA), were evaluated. Statistical analysis was performed with SPSS 23.0 using the Kruskal-Wallis and Mann-Whitney tests (P<0.05). 

Results: a total of 622 men were divided as follow into the groups: marijuana (n=74), tobacco smokers (n=144), infertile (n=125) and fertile group (n=279). Seminal ROS levels were higher in the marijuana group (14.31&[plusmn]31.63 x104cpm/20x106 sperm) as compared with tobacco (0.70&[plusmn]1.55 x104cpm/20x106 sperm) and fertile groups (0.68&[plusmn]1.67 x104cpm/20x106 sperm) (P<0.01). Comparing marijuana and tobacco groups, the first had worst overall semen parameters including: sperm concentration, total sperm count, total progressive sperm count, progressive motility, and sperm morphology by both WHO and strict criteria (all P&[le]0.01). The mechanism was identified and is induction of oxidative stress through the generation of intracellular ROS by tetrahydrocannabinol the major component in marijuana. Estradiol levels were significantly lower (10.04&[plusmn]12.38ng/dl) in marijuana group (P<0.001) while testosterone, LH and FSH levels were within reference range in all groups. 

Conclusions: Both marijuana and tobacco are deleterious for testicular function but marijuana caused more sperm functional defects than tobacco, mediated by excess intracellular ROS generation. 

Funding: Androscience High Complexity Clinical and Research Andrology Laboratory. 


PD28-07 
Heart Healthy Diet and Erectile Dysfunction in the Health Professionals Follow-Up Study 
Scott R. Bauer, Meir J. Stampfer, Edward Giovannucci, Eric B. Rimm, Stacey A. Kenfield 

Introduction: Erectile dysfunction (ED) affects more than half of men over age 70 and leads to decreased quality of life. Non-pharmacologic treatments, such as smoking cessation and weight loss, are attractive options because they are inexpensive, well tolerated, and have additional health benefits, such as decreased cardiovascular risk. However, it remains unknown whether heart healthy dietary patterns are associated with ED. 

Methods: We conducted a prospective analysis of 26,246 men aged 40 to 75 years old enrolled in the Health Professionals Follow-Up Study. Erectile function was assessed with questionnaires in 2000, 2004, and 2008. Men were included if they reported 'good' or 'very good' erectile function in 2000 and incident ED was defined as 'poor' or 'very poor' function during follow-up. Dietary data was self-reported on validated food-frequency questionnaires completed every 4 years and used to calculate Mediterranean Diet and Alternative Health Eating Index (AHEI) scores, which were cumulatively updated. We used multivariable Cox proportional hazards models to adjust for confounders and compute hazard ratios (HR) for incident ED (N = 2,931). We evaluated for a priori effect modification by age. 

Results:
Higher Mediterranean Diet and AHEI scores were both associated with decreased risk of incident ED. Men in the highest, compared to the lowest, category of Mediterranean Diet score had a 14% lower risk of developing ED (HR = 0.86; 95% CI 0.82 - 0.91). Similarly, men in the highest quintile of AHEI score had a 17% lower risk of developing ED (HR = 0.83, 95% CI 0.77 - 0.89), compared to men in the lowest quintile. The inverse associations between Mediterranean Diet score or AHEI and incident ED were strongest among men aged <60 years (p-interaction = 0.004 and 0.006, respectively). When associations with individual score components were examined, higher intakes of legumes, fruit, vegetables, fish, and long-chain (n-3) fats were associated with decreased risk of ED. Conversely, total, red, and processed meat and trans fat intakes were positively associated with risk of ED. Other score components, including dairy, nuts, sugar-sweetened beverages, whole grains or cereals, and alcohol were not associated with ED. 

Conclusions: Heart health dietary patterns, including Mediterranean Diet and AHEI, are associated with decreased risk of incident ED in this prospective cohort study. Our findings support the evaluation of dietary interventions for the prevention or treatment of ED. 

Funding: Dr. Bauer was supported by grant 1K12DK111028 from the National Institute of Diabetes, Digestive, and Kidney Disorders. 


PD19-08 Marijuana, Alcohol, ED and Depression: Epidemiologic Correlations with BPH/LUTS 
Heather Carmichael, Granville Lloyd 

Introduction: Benign prostatic hyperplasia with lower urinary tract symptoms (BPH/LUTS) is a disease with high prevalence, societal impact and cost. Our aim was to explore associations including marijuana usage, alcohol usage and other medical comorbidities with BPH/LUTS treatment. 

Methods: We queried our hospital network database of nearly two million patients for data from the electronic medical record between January 2011 and October 2018. Men over the age of 40 who were on medical therapy for LUTS (selective alpha blockade and/or finasteride) were included. Patients with only one recorded visit or with a diagnosis of bladder/prostate malignancy were excluded. Medical therapy for LUTS was defined based on prescriptions for tamsulosin, alfuzosin and/or finasteride 5mg. Alcohol (AL) and marijuana (MJ) use were found from diagnosis code and/or social history text. Medical comorbidities including depression, obesity or metabolic syndrome (MetS), hypertension (HTN), erectile dysfunction (ED), hypogonadism, and diabetes (DM) were identified based on ICD-9/10 codes. Multivariable logistic regression was used to control for multiple additional confounders including patient age, race, insurance type, BMI, and vital signs. Alcohol (AL) and marijuana (MJ) use were found from diagnosis code and/or social history text. Medical diagnoses were based on ICD-9/10 codes. Multiple logistic regression was used to control for multiple confounders including patient age, race, insurance type, comorbidities, BMI, and vital signs. 

Results:
173,469 patients were included; 20,548 (11.9%) were on medical treatment for LUTS. On univariable analysis, MJ use and ED were associated with increased risk of being on a LUTS medication. AL use was associated with decreased risk of being on a LUTS medication. On multivariable analysis, MJ remained associated with an increased risk of LUTS medication, as did ED and depression. AL use had no significant association with LUTS treatment. (TABLE) 

Conclusions: Men with depression, marijuana usage, HTN, MetS, ED, hypogonadism and DM were more likely to be treated for LUTS, but alcohol use use was not associated. Marijuana use is a newly described association with LUTS and understanding of this interplay is desirable. 

Funding: Supported by the Health Data Compass Data Warehouse project (healthdatacompass.org) 

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