Aruna V. Sarma

Obesity and Benign Prostatic Hyperplasia: Clinical Connections, Emerging Etiological Paradigms and Future Directions

PURPOSE Benign prostatic hyperplasia is a highly prevalent disease in older men with substantial adverse effects on public health. Classic etiological paradigms for benign prostatic hyperplasia focus on nonmodifiable risk factors. However, obesity also potentially promotes benign prostatic hyperplasia. MATERIALS AND METHODS We performed a structured, comprehensive literature review to identify studies of obesity, benign prostatic hyperplasia, lower urinary tract symptoms and physical activity. RESULTS A preponderance of published evidence suggests strong positive associations of obesity with benign prostatic hyperplasia and lower urinary tract symptoms. This evidence encompasses most established metrics of adiposity, including body mass index, waist circumference and waist-to-hip ratio, and falls under 3 general categories, including prostate volume, clinical benign prostatic hyperplasia and lower urinary tract symptoms. 1) Prior studies consistently showed that increased adiposity is positively associated with radiographically determined prostate volume and enlargement, suggesting that obesity promotes prostate growth. 2) Most studies revealed that obesity increases the risk of clinical benign prostatic hyperplasia by several measures, including the initiation of benign prostatic hyperplasia medical treatment, noncancer prostate surgery, physician diagnosed benign prostatic hyperplasia, histological diagnosis and urinary flow rate. 3) Prior studies demonstrated that obesity increases the risk of lower urinary tract symptoms, as measured by a validated questionnaire. Also, most studies showed that physical activity significantly decreases the risk of benign prostatic hyperplasia. CONCLUSIONS Obesity markedly increases the risk of benign prostatic hyperplasia. Since physical activity decreases the risk of benign prostatic hyperplasia, these observations support the development of novel prevention strategies and treatment targeted toward adiposity, weight loss and lifestyle.

Comparison of lower urinary tract symptom severity and associated bother between community-dwelling black and white men: the Olmsted County Study of Urinary Symptoms and Health Status and the Flint Men’s Health Study

OBJECTIVES To determine the magnitude of racial disparity in lower urinary tract symptom (LUTS) severity and bother by combining two large comparable epidemiologic studies of community-dwelling white and black men, thereby avoiding many of the referral biases present in previous studies. Prior studies evaluating racial differences in benign prostatic hyperplasia have been hampered by selection bias, because nearly all have used surgical treatment as a marker for benign prostatic hyperplasia. METHODS Data from the Olmsted County Study of Urinary Symptoms and Health Status and the Flint Mens Health Study were combined for a total study sample of 2480 men. We examined LUTS severity and associated bother as measured by the self-administered American Urological Association Symptom Index and Symptom Problem Index. RESULTS Overall 34% of white men reported moderate/severe LUTS compared with 41% of black men (P <0.001). These patterns were consistent across age and persisted after adjustment for age and other sociodemographic factors. The relationship between LUTS severity and bother differed by race in that black men reported less bother for each unit increase in LUTS (P <0.001). CONCLUSIONS In contrast to studies based on clinical populations, our community-based study demonstrated greater LUTS severity in black men compared with white men but black men reported less bother for any given level of LUTS severity. Although these findings suggest a racial disparity in benign prostatic hyperplasia, additional studies of anatomic, physiologic, and molecular factors may clarify whether these racial differences are real or due to sociocultural differences in reporting symptom morbidity.

Bladder Management After Spinal Cord Injury in the United States 1972 to 2005

PURPOSE Studies have shown that bladder management with an indwelling catheter for patients with spinal cord injury is associated with more urological complications such as stones, urinary infection, urethral strictures and bladder cancer. However, little is known about actual bladder management for these patients in clinical practice. MATERIALS AND METHODS Using the National Spinal Cord Injury Database the bladder management method was determined at discharge from rehabilitation and at each 5-year followup period for 30 years. RESULTS At discharge from rehabilitation (24,762 patients) the selection of bladder management with a condom catheter decreased steadily from a peak of 34.6% in 1972 to a low of 1.50% in 2001. The use of clean intermittent catheterization increased from 12.6% in 1972 to a peak of 56.2% in 1991. Indwelling catheter use initially decreased from 33.1% in 1972 to 16.5% in 1991 but increased to 23.1% in 2001. Of 12,984 individuals with followup data those originally using an indwelling catheter for bladder management were unlikely to switch to another method, with 71.1% continuing to use an indwelling catheter at 30 years. Individuals using clean intermittent catheterization and condom catheterization at discharge home did not continue to use these methods with only 20% and 34.6% remaining on the same management, respectively. CONCLUSIONS With time bladder management with clean intermittent catheterization has increased in popularity. However, only 20% of patients initially on clean intermittent catheterization remained on this form of bladder management. More research on the safety of each of these methods needs to be performed to provide better guidance to aid with this decision.

Features of the metabolic syndrome and prostate cancer in African-American men

Metabolic syndrome refers to a cluster of conditions that includes hypertension, dyslipidemia, central adiposity, and high blood glucose levels. Over the past decade, a growing body of literature suggests that metabolic syndrome may be associated with several different forms of cancer. Because prostate cancer risk is highest among African Americans, and these men, similarly, are more prone to developing specific features of the metabolic syndrome, including hypertension and type‐2 diabetes, any relationships would have a significant impact on developing strategies for the primary prevention of prostate cancer.

Insulin-like growth factor-1, insulin-like growth factor binding protein-3, and body mass index: clinical correlates of prostate volume among Black men

OBJECTIVES To examine the relationship between insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein-3 (IGFBP-3), and body mass index and prostate volume, as a surrogate marker for benign prostatic hyperplasia, in a community-based sample of black men. Epidemiologic studies examining the role of IGF-1 and IGFBP-3 suggest that increased levels of serum IGF-1 and decreased levels of serum IGFBP-3 are associated with an increased risk of prostate cancer. Few studies have examined these factors with respect to benign prostatic hyperplasia, and these have been limited to white men. METHODS The study population consisted of a sample of 364 black men, 40 to 79 years of age, residing in Genesee County, Michigan. Men with prostate cancer or prior prostate surgery were excluded. All subjects completed a clinical examination, which included a complete urologic examination with transrectal ultrasonography, anthropometric measurements, and serum assays for IGF-1 and IGFBP-3. RESULTS Multivariable regression models demonstrated that prostate volume increased with increasing age (P <0.0001) and body mass index (P = 0.03). IGFBP-3 rather than IGF-1 was positively associated with increasing prostate volume (P = 0.003). CONCLUSIONS This is the largest study describing the relationships between IGF-1, IGFBP-3, and body mass index and prostate volume, and the only study in black men. Although earlier studies demonstrated an association between IGF-1 and prostate cancer risk, our findings indicate that IGFBP-3 is more relevant for prostate enlargement, suggesting that IGF-1 and IGFBP-3 may play different pathophysiologic roles in benign and malignant prostatic conditions.

Effect of Intensive Glycemic Therapy on Erectile Function in Men With Type 1 Diabetes

PURPOSE We determined whether intensive glycemic therapy reduces the risk of erectile dysfunction in men with type 1 diabetes enrolled in the Diabetes Control and Complications Trial. MATERIALS AND METHODS The Diabetes Control and Complications Trial randomized 761 men with type 1 diabetes to intensive or conventional glycemic therapy at 28 sites between 1983 and 1989, of whom 366 had diabetes for 1 to 5 years and no microvascular complications (primary prevention cohort), and 395 had diabetes for 1 to 15 years with nonproliferative retinopathy or microalbuminuria (secondary intervention cohort). Subjects were treated until 1993, and followed in the Epidemiology of Diabetes Interventions and Complications study. In 2003 we conducted an ancillary study using a validated assessment of erectile dysfunction in 571 men (80% participation rate), 291 in the primary cohort and 280 in the secondary cohort. RESULTS Of the participants 23% reported erectile dysfunction. The prevalence was significantly lower in the intensive vs conventional treatment group in the secondary cohort (12.8% vs 30.8%, p = 0.001) but not in the primary cohort (17% vs 20.3%, p = 0.49). The risk of erectile dysfunction in primary and secondary cohorts was directly associated with mean HbA1c during the Diabetes Control and Complications Trial, and Epidemiology of Diabetes Interventions and Complications combined. Age, peripheral neuropathy and lower urinary tract symptoms were other risk factors. CONCLUSIONS A period of intensive therapy significantly reduced the prevalence of erectile dysfunction 10 years later among those men in the secondary intervention cohort but not in the primary prevention cohort. Higher HbA1c was significantly associated with risk in both cohorts. These findings provide further support for early implementation of intensive insulin therapy in young men with type 1 diabetes.

Benign Prostatic Hyperplasia and Lower Urinary Tract Symptoms

Lower urinary tract symptoms affect more than half of older men. Options for bothersome symptoms include α-adrenergic-receptor blockers, 5α-reductase inhibitors, phosphodiesterase-5 inhibitor therapy, and antimuscarinic therapy.

Associations Between C-Reactive Protein and Benign Prostatic Hyperplasia/Lower Urinary Tract Symptom Outcomes in a Population-based Cohort

Inflammation may play a role in the development of benign prostatic hyperplasia and/or lower urinary tract symptoms (LUTS). Higher levels of C-reactive protein (CRP) may therefore be associated with the development of these outcomes. The authors examined the association of CRP levels measured in 1996 with rapid increases in prostate volume, prostate-specific antigen levels, and LUTS as well as rapid decreases in peak flow rates (through 2005) in a population-based cohort of men residing in Olmsted County, Minnesota. Men with CRP levels of > or =3.0 mg/L were more likely to have rapid increases in irritative LUTS (odds ratio (OR) = 2.14, 95% confidence interval (CI): 1.18, 3.85) and rapid decreases in peak flow rates (OR = 2.54, 95% CI: 1.09, 5.92) compared with men with CRP levels of <3.0 mg/L. CRP levels were not significantly associated with rapid increases in prostate volume, obstructive LUTS, or prostate-specific antigen levels. Associations were attenuated after adjusting for age, body mass index, hypertension, and smoking history (irritative LUTS: OR = 2.00, 95% CI: 1.04, 3.82; peak flow rate: OR = 2.45, 95% CI: 0.73, 8.25). These results suggest that rapid increases in irritative LUTS and rapid decreases in peak flow rates may be due to inflammatory processes.

Concomitant Longitudinal Changes in Frequency of and Bother From Lower Urinary Tract Symptoms in Community Dwelling Men

PURPOSE Care for men with benign prostatic hyperplasia consumes a sizable amount of health care resources, which is largely driven by bother from lower urinary tract symptoms. While cross-sectional studies have demonstrated a strong correlation between frequency of symptoms and associated bother, there are few longitudinal data demonstrating how these track together. MATERIALS AND METHODS In 1989, 2,115 white men between 40 and 79 years old were recruited from a random sample of the Olmsted County population. These men completed a self-administered questionnaire that assessed lower urinary tract symptom severity and associated bother with questions similar to those in the American Urological Association Symptom Index. Questionnaires were completed biennially thereafter through 1996. RESULTS Annualized changes in symptom score increased from a median of 0.02 per year (25th, 75th percentile -0.35, 0.60) for men in their forties to 0.43 (-0.12, 1.16) for men in their sixties. The median change in bother scores was 0 (-0.30, 0.29) across all ages. The correlation between longitudinal symptom score slopes and bother score slopes was 0.55 (p <0.001) overall and did not differ substantively across age. CONCLUSIONS These results demonstrate that there is a great deal of variability between individuals in the amount of longitudinal change in lower urinary tract symptom severity and bother. While for bother, there is little change across individuals on average, within individual frequency and bother track together fairly closely. However, there remain some men with increases in frequency who do not report similar increases in bother, possibly representing some component of adaptation or acceptance of worsening symptom severity with age.

Genetic polymorphisms in CYP17 , CYP3A4 , CYP19A1 , SRD5A2 , IGF-1 , and IGFBP-3 and prostate cancer risk in African-American men: The Flint Men's Health Study

Association studies have examined the significance of several candidate genes based on biological pathways relevant to prostate carcinogenesis, including both the androgen and insulin‐like growth factor pathways. Clinical and epidemiologic evidence suggest that androgens, specifically testosterone and dihydrotestosterone (DHT) are important not only in normal prostate growth but in the pathogenesis of prostate cancer. Similarly, the insulin‐like growth factor‐1 (IGF‐1) signaling pathway regulates both cellular proliferation and apoptosis. Therefore, genes involved in the biosynthesis, activation, metabolism and degradation of androgens and the stimulation of mitogenic and antiapoptotic activities of prostate epithelial cells represent important candidates for affecting the development and progression of prostate cancer.