Cause Of Benign Prostatic Hyperplasia Research Articles

Oestrogen and benign prostatic hyperplasia: effects on stromal cell proliferation and local formation from androgen

Oestrogens have been implicated as a cause of benign prostatic hyperplasia (BPH). Previous animal studies led to the hypothesis that oestrogens can stimulate prostate growth, resulting in hyperplasia of the gland. In humans, the precise role of oestrogens in BPH pathogenesis is currently unclear. We investigated the direct effects of oestradiol on the proliferation of BPH-derived prostate cells in culture. Oestradiol (10(-7) and 10(-6) M) moderately increased the proliferation of stromal cells in culture; this stimulation was antagonised by anti-oestrogen ICI 182 780, indicating an oestrogen receptor (ER)-mediated mechanism. By contrast, oestradiol had no effects on the proliferation of epithelial cells in culture. Parameters that can determine the response of stromal cells to oestrogens, including expression of the two ER subtypes and aromatase activity, were investigated. ER beta expression in stromal cells in culture was demonstrated by immunohistochemistry and western blot analysis, and was confirmed by semi-quantitative RT-PCR showing higher expression of ER beta than ER alpha mRNA in stromal cells. Aromatase, the enzyme that converts androgen precursors to oestrogens, was also examined. Aromatase mRNA and activity were detected in stromal, but not epithelial cells in culture, suggesting a mechanism whereby oestrogen concentrations can be regulated in the BPH stroma. Taken together, these findings support the hypothesis that oestrogens play a role in the pathogenesis of BPH, a disease characterised predominantly by stromal overgrowth.

The overlooked cause of benign prostatic hyperplasia: prostatic urethral angulation

Benign prostatic hyperplasia (BPH) is one of the most common problems faced by aging men and can be associated with bothersome lower urinary tract symptoms that affect quality of life by interfering with normal daily activities and sleep patterns. Despite the clinical importance of BPH, its pathogenesis is still poorly understood. Previously, our understanding of BPH was centered on bladder outlet obstruction being secondary to benign prostatic enlargement. However, prostate size itself is not correlated with the urine flow rate and symptomatology. The prostatic urethra is a bend tube and the increased prostatic urethral angulation shows a higher bladder neck on cystoscopic examination. Although some urologists suspected that the higher bladder neck might be a causal factor for BPH, the clinical significance of prostatic urethral angulation was previously underestimated. In this study, we propose a new hypothesis that prostatic urethral angulation is a causal factor for BPH. By applying the concept of fluid dynamics to the process of urination in the prostatic urethra, we show that the energy loss in this bending tube (the prostatic urethra) can occur during micturition and it increases proportionally to prostatic urethral angulation; this energy loss results in a decrease of the urine velocity and accordingly, the urine flow rate is inversely associated with prostatic urethral angulation. We also propose that BPH involves prostatic urethral angulation as well as the classical BPH triad of prostatic enlargement, bladder outlet obstruction, and symptomatology. Our hypothesis suggests that prostatic urethral angulation is an overlooked cause of bladder outlet obstruction and is a causal factor of BPH, and provides novel insight into the pathogenesis of BPH. Ultimately, the relationship between prostatic urethral angulation and urine flow rate, and other clinical factors including urodynamic parameters, the symptomatology, the response to treatment, and disease progression, need to be investigated in a clinical setting.

Turbulent urinary flow in the urethra could be a causal factor for benign prostatic hyperplasia

Benign prostatic hyperplasia (BPH) is the most common form of prostate disease in middle-aged and elderly men, and leads to severe impairment later in life. Despite its significant impact on public health, the underlying cause of BPH is yet to be determined. This hypothesis proposes a new causal factor for BPH. Applying concepts of dynamics of fluids to the process of urination it could be stated that a turbulent urinary flow through the passage of the urethra. The turbulent urinary flow in the urethra applies pressure and stretch forces to the surrounding tissue. This stimulus repeated over time and coupled with age-related changes of the urethral tissue could contribute to the development of BPH. In support of this hypothesis, several mechanotransduction studies have shown that vibration and pressure forces applied to different cell tissues can provoke cellular and molecular changes. Another supportive data is the presence of the hyperplasic reaction surrounding the urethra specifically located in the transition zone, the only zone where BPH develops. It is crucial to identify causal factors to understanding the disease and to determine effective primary prevention strategies. Future studies of the dynamics of fluids in the urethra are warranted. The finding of significant forces transmitted to the periurethral tissue from a turbulent urinary flow could give us the clue to the underlying cause of BPH. If this hypothesis proves to be valid there are several primary prevention measures that could be implemented to impede the development of BPH. Educational intervention measures in younger populations to avoid frequent urinary retention and active urination (process of forcing the urine through the urethra at a high velocity) could be considered. Studies of the impact of turbulence in the standing vs. sitting position during urination in men should also be considered.

Risk Factors for Benign Prostatic Hyperplasia in South Korean Men

Objectives: Benign prostatic hyperplasia (BPH) is the most common prostate disease in middle-aged and elderly men, and leads to severe impairment in later life. Despite the significant effect on public health, the causes of BPH have received little attention. Identifying risk factors for BPH is crucial for understanding the etiology and for determining effective interventions or targeting strategies. Methods: This survey was performed in two steps: (1) a pilot study was first conducted prior to the main study in order to estimate baseline characteristics, and (2) the main study investigated the prevalence and risk factors of BPH using clinical diagnostic tests and a questionnaire. A total of 641 males, aged 50–79 years, participated in this community-based cross-sectional study. Results: Age was the only significant demographic risk factor of BPH. The presence of chronic bronchitis and a high prostate-specific antigen (PSA) level increased the risk by three- and twofold, respectively. The risk decreased as drinking frequency increased. Physical activity 3–5 times/week reduced the risk relative to being active less than twice per week; however, engaging in physical activity nearly everyday increased the risk 1.7-fold relative to being active up to twice per week. Conclusions: Although BPH has been considered a disease that is unavoidable with advancing age, the clear identification and control of the underlying risk factors might allow effective prevention by placing a special emphasis on those at risk.

Management of benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is a common cause of morbidity among older men. Primary care physicians need to develop expertise in its management. The causes of BPH are unknown; aging and the presence of male androgens are the dominant risk factors. Obtaining a medical history is a key step in assessing whether lower urinary tract symptoms are due to BPH or to some other process. A reliable and valid seven-item questionnaire has been developed to objectively assess symptom severity. A focused physical examination including a digital rectal exam should be performed, as well as a urinalysis and serum creatinine. Optional tests include uroflowmetry, post-void residual urine, and prostate-specific antigen measurements. BPH is treated primarily to improve the quality, rather than increase the quantity, of life. Optimal decisions about treatment are best made by a clinician and an informed patient working together.

Association between Family History of Benign Prostatic Hyperplasia and Urinary Symptoms: Results of a Population-based Study

Baseline measurements for a population-based prospective cohort study were used to assess the association between family history of enlarged prostate and urinary symptoms. Between December 1989 and March 1991, a group of randomly selected men aged 40-79 years from Olmsted County, Minnesota, was administered a previously validated questionnaire that included questions with wording close to that of the American Urological Association's Symptom Index. A detailed family history of an enlarged prostate was obtained by personal interview, and peak urinary flow rates were measured for each participant. Of the 2,119 men, 440 (21 percent) reported a family history of an enlarged prostate. The age-adjusted odds of having moderate or severe urinary symptoms were elevated among those with a family history relative to those without (odds ratio = 1.3, 95 percent confidence interval 1.1-1.7). With simultaneous control for effects of age and worry about urologic function, the odds ratio remained at 1.3 (95 percent confidence interval 1.0-1.6). Furthermore, this risk was greater for men with relatives diagnosed at a younger age (odds ratio = 2.5, 95 percent confidence interval 1.5-4.3). Men with a family history were also 1.3 times as likely to have an impaired peak urinary flow rate. These findings suggest that men with a family history of an enlarged prostate may be at increased risk for development of symptoms and signs suggestive of benign prostatic hyperplasia and that this risk is greater in men with relatives diagnosed at a younger age. Recognition of this association may help to target early interventions and may lead to further clues about the causes of benign prostatic hyperplasia.

A Unifying Hypothesis that Links Benign Prostatic Hyperplasia and Prostatic Intraepithelial Neoplasia with Prostate Cancer: Invited Comments

Prostatic Intraepithelial Neoplasia (PIN) and prostatic cancer (PCA) are not caused by infection, allergic reaction, inadequate immunological response, ischemia, ageing, systemic hormones, carcinogens, nor prostatic ductal contents. PIN and PCA are apparently caused by increased inner acinar pressure due to partially blocked draining ducts. Only this explanation can account for all the observations about PIN and PCA. All other possible causes are disproved by specific observations. In order to further clarify the cause of PIN and PCA, it is important to discover if peripheral zone lesions cluster around ducts or blood vessels. PIN patterns are the morphological precursors of both PCA and prostatic cysts. Different PIN patterns represent different adaptive stages to increasing inner acinar pressure. The immediate tissue cause of PCA is PIN disruption seeding the stroma with high-grade PIN (HGPIN) cells. These cells, programmed for adaptive proliferation and mobility in PIN, are sufficient in the stroma to cause all stages and patterns of invasive PCA. No mutated cells are necessary. For reasons given, the primary cause of the initial ductal blockage that results in PIN and PCA cannot be inflammation, stones, proteineous plugs, infarction, venus thrombosis, ductal hyperplasia, nor a constricted penis at ejaculation. Only benign prostatic hyperplasia (BPH) can explain all the facts and is thus the primary cause of the ductal blockage resulting in cysts, PIN and PCA. The main causes of BPH are apparently disuse atrophy of sexual and abdominal muscles, and atherosclerosis of the capsular branch of the prostatic artery, causes atypical adenomatous hyperplasia (AAH) in the transition zone. The resulting muscular and glandular atrophy decreases local and general growth inhibitors. New growth in the adult prostate is abnormal because epithelial cells grow into ducts rather into the stroma. In such ducts, the growths cannot receive stromal growth inhibitory signals, and thus continue to grow indefinitely and result in BPH, AAH-adenosis, blockage of ducts, cysts, PIN and PCA.

The origin and development of benign prostatic hyperplasia. An age-dependent process.

Although the exact cause of benign prostatic hyperplasia (BPH) is not well defined, it is thought to occur as the result of epithelial-stromal interactions in the appropriate hormonal milieu. Benign prostatic hyperplasia originates in the periurethral and transition zones of the prostate in a microscopic (histologically identifiable) state as early as the third decade of life. With advancing age and the presence of androgens, approximately 50% of microscopic BPH will develop into macroscopic (palpably enlarged prostate) BPH. However, clinically significant BPH necessitating treatment will develop in only 50% of men with an enlarged prostate gland. In the United States, the estimated risk of a 50-year-old man undergoing a prostatectomy in his lifetime is approximately 25% to 40%. If left untreated, a significant number of symptomatic patients will remain stable or improve without adverse sequelae.

Development of a model for the induction of estrogen‐related prostatic hyperplasia in the dog and its response to the aromatase inhibitor 4‐hydroxy‐4‐androstene‐3,17‐dione: Preliminary results

Although the presence of the testes is an absolutely necessary prerequisite for benign prostatic hyperplasia (BPH) to occur, the role of androgens in the cause of BPH is still controversial. There are increasing signs for a decisive role of estrogens in that connection. We treated castrated beagle dogs of known age with androstenedione (an androgen that can be aromatized) and with the aromatase inhibitor 4-hydroxyandrostendione. Six or 9 months of treatment with androstenedione resulted in a BPH characterized by typical androgenic effects--ie, hyperplasia and hypertrophy of the epithelium--and by typical estrogenic effects--, stimulation of the stroma, especially of the smooth muscles, and cystic enlargement of the tubules. These estrogen-related effects could be clearly antagonized by the simultaneous treatment with the aromatase inhibitor 4-hydroxyandrostenedione. The hyperplastic effects on the epithelium were also partly antagonized by the aromatase inhibitor. Our preliminary results further strengthen the effectiveness of aromatase inhibitors as an alternative treatment of human BPH, which is thought to be predominantly a stromal disease.