Pathogenesis Of BPH Research Articles

Cigarette smoking: A review of possible associations with benign prostatic hyperplasia and prostate cancer

There are conflicting data on the effect of cigarette smoking on serum levels of the various sex hormones. Some studies suggest that cigarette smoke produces an antiestrogenic effect. Smoking may also affect the metabolism of other sex steroids such as testosterone and adrenal hormones, and thereby influence the incidence of benign and malignant growth of the prostate. Epidemiologic studies analyzing a possible association between cigarette smoking and prostate cancer are not conclusive, although some show a positive relationship. The etiology of BPH is undoubtedly multifactorial. Estrogens as well as androgens may be involved in the pathogenesis of BPH. There are several studies that indicate that cigarette smokers have a lower likelihood of requiring surgery for BPH. Growth of the prostate may not correlate with serum levels of androgens and estrogens. The local hormonal milieu of the target cells in the prostate are probably more critical than the more easily measured serum levels. This review examines the literature dealing with cigarette smoking and both BPH and prostate cancer. If there is an effect, then elucidation of the mechanism by which smoking affects the growth of the prostate may improve our understanding of BPH and prostate cancer, and may suggest preventive strategies for high risk groups.

Quantifying the Smooth Muscle Content of the Prostate Using Double-Immunoenzymatic Staining and Color Assisted Image Analysis

The primary objective of the present study was to develop a method for quantifying the smooth muscle content of the prostate adenoma. A double immunoenzymatic staining technique was coupled with color assisted image analysis to determine the area density of the smooth muscle within the prostate adenoma. Eight males with symptomatic BPH underwent transrectal biopsy of the prostate. Four micron thick tissue sections were used for the double immunoenzymatic staining process. Rabbit anti-desmin and mouse anti-human prostatic acid phosphatase antibodies were used to selectively bind smooth muscle and prostatic epithelium, respectively. The two different tissue antigens were identified with peroxidase-antiperoxidase (PAP) and alkaline phosphatase-antialka-line phosphatase techniques. The alkaline phosphatase activity and peroxidase activity were developed with fast red and DAB chromogens. The BQ MEG IV Vista color system image analysis was used to discriminate color differences from the stained tissue sections. The thresholds were set to identify smooth muscle (dark brown), epithelium (red), fibrous tissue (pale brown), and glandular lumina (colorless). The mean area density of smooth muscle, fibrous tissue, glandular epithelium, and glandular lumina was 22%, 54%, 16%, and 9%, respectively. The present study suggests that a significant component of the prostate adenoma is smooth muscle. The application of this technique will be utilized to provide further insights into the role of smooth muscle in the pathogenesis and therapy of BPH.

Medical management of benign prostatic hyperplasia

Medical management of clinical BPH is a reality. The only effective nonsurgical treatment now recommended is aimed at relieving the dynamic component of clinical BPH. Pharmacologic treatment using alpha-adrenoceptor antagonists may be used appropriately to manage patients with prostatism who are poor surgical risks but who could benefit from reduced sympathetic tone. In addition, alpha blockers are used to relieve acute retention, and to prevent retention when increased sympathetic discharge is expected. Thus far, nonsurgical therapy aimed at reducing the mechanical obstruction associated with BPH by prostatic size reduction has failed to produce consistent objective improvement. However, several drugs are now being investigated and may be effective for reducing prostatic size in patients with BPH. Clinical trials are complicated by a number of factors, especially very variable symptoms. Moreover, reduction in prostatic size induced by drugs is not permanent and regrowth occurs with drug withdrawal, necessitating chronic treatment. Ideally, future research should be aimed at the prevention of BPH at an early age. However, this presupposes a better understanding of the pathogenesis of BPH. BPH may not be a single, variable disease but a family of diseases with a number of predictable clinical courses. In the future, we should pay particular attention to histologic variability, to see if in fact different pathologic forms of BPH follow different clinical patterns. If urologists are to keep their predominant position in managing the patient with BPH, they will have to keep informed of medical treatment trials and of potential alternative treatment strategies to prostatectomy.

Testosterone Metabolism of Fibroblasts Grown From Prostatic Carcinoma, Benign Prostatic Hyperplasia and Skin Fibroblasts

The metabolism of [1,2,6,7-3H]testosterone was assessed in fibroblast monolayers derived from tissue of 5 prostates with benign hyperplasia (BPH), 4 prostates with carcinoma (PC), and 3 biopsy samples of skin, 2 nongenital skin (NG) and 1 genital skin. The following metabolites could be identified: androstanedione androstenedione, dihydrotestosterone, androsterone, epiandrosterone, androstane-3α, 17β-diol and androstane-3β, 17β-diol. Testosterone was metabolized much more rapidly in fibroblasts originating from prostatic tissue than in fibroblasts derived from NG. A significantly higher formation of 5α-androstanes and 3α-hydroxysteroids could be observed in fibroblasts from BPH as compared to PC. 17-ketosteroid formation exceeded 5α-androstane formation in BPH, whereas 5α-reduction was the predominant pathway in fibroblasts grown from PC and NG. Since testosterone metabolism in fibroblasts of prostatic origin therefore resembles in many aspects that in whole prostatic tissue, fibroblasts grown from prostatic tissues might be a valuable tool for further investigation of the pathogenesis of human BPH and PC.

Hormone blood levels and their inter-relationships in normal men and men with benign prostatic hyperplasia (BPH).

In 128 non-hospitalized men (age range 36-65 years) rectal palpation revealed in 54 cases an enlargement of the prostate (group II), which was very distinct in 20 cases (group III). The measurement of testosterone (T), 5alpha-dihydrotestosterone (DHT), 5alpha-androstane-3alpha,17beta-diol (3alpha-diol) oestradiol (Oe2), sex-hormone-binding-globulin binding capacity (SHBG), luteinizing hormone (LH), follicle stimulating hormone (FSH) and prolactin (Prl) in the blood of normal men (group I) and those with BPH (group II or III) demonstrated no significant differences between the three groups when respective age ranges were compared. A significant increase of FSH and decrease of 3alpha-diol with age was seen in the normal group (I), which was similar but less pronounced in BPH (groups II and III). A distinct increase of DHT with age was found in BPH (group II), which was not so dominant in normal men (group I). From these data it is concluded that the conversion of DHT to 3alpha-diol might be reduced in older males independent from the occurrence of BPH and that the hyperplastic prostate possibly secretes significant amounts of DHT into the circulation. These results are discussed with respect to their possible role in the pathogenesis of BPH.

Comparison of androgen metabolites in benign prostatic hypertrophy (BPH) and normal prostate.

5 alpha-Dihydrotestosterone (DHT) and androstanediols (diols) have been measured in human prostate tissue. DHT levels in surgical specimens of prostate from 8 patients with BPH averaged 5.6 +/- 0.93 S.E. ng/g and were significantly greater than (P less than 0.01) values of 2.1 +/- 0.32 S.E. ng/g in 6 normal prostates obtained post-mortem from males less than 50 yrs old. Androstanediols averaged 2.3 +/- 0.35 S.E. ng/g in the BPH specimens compared to values of 10.2 +/- 2.4 S.E. ng/g in the normal prostates (P less than 0.01). This significantly higher (P less than 0.001) ratio of diols/DHT in the normal (5.1 +/- 0.93 S.E.) compared to the BPH prostate (0.45 +/- 0.08 S.E.) suggests that a decrease in 3-hydroxysteroid oxido-reductase, which converts DHT to diol, may be an important clue to the pathogenesis of BPH.