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PubMed2001

5alpha-reductase activity in the prostate.

The prostate gland depends on androgen stimulation for its development and growth. However, testosterone is not the major androgen responsible for growth of the prostate. Testosterone is converted to dihydrotestosterone (DHT) by the enzyme Delta(4), 3 ketosteroid, 5alpha-reductase in prostatic stromal and basal cells. DHT is primarily responsible for prostate development and the pathogenesis of benign prostatic hyperplasia (BPH). Inhibitors of 5alpha-reductase reduce prostate size by 20% to 30%. This reduction in glandular tissue is achieved by the induction of apoptosis, which is histologically manifested by ductal atrophy. Inhibition also diminishes the number of blood vessels in the prostate because of a reduction in vascular-derived endothelial growth factor. 5alpha-Reductase occurs as 2 isozymes, type 1 and type 2, with the prostate expressing predominantly the type-2 isozyme, and the liver and skin expressing primarily the type-1 isozyme. Patients have been identified with deficiencies in the type-2 5alpha-reductase, but not type 1. Knockout mice with the type-2 5alpha-reductase demonstrate a phenotype similar to that seen in men with 5alpha-reductase deficiency. Type-1 5alpha-reductase knockout male mice are phenotypically normal. Enzymatic activity for 5alpha-reductase or immunohistochemical detection has been noted in other genitourinary tissues, such as the epididymis, testes, gubernaculum, and corporal cavernosal tissue. Preputial skin predominately expresses the type-1 5alpha-reductase, whereas stromal cells in the seminal vesicle also express type-2 isozyme. However, epithelial cells in the epididymis, but not surrounding stroma, express type-1 5alpha-reductase. In addition to influencing prostatic growth, 5alpha-reductase also influences the expression of neuronal nitric-oxide synthase in the corpus cavernosum. The contribution of DHT in the serum, which is partially derived from type-1 5alpha-reductase in the liver and the small amount of type-1 5alpha-reductase in the prostate, may play a role in maintaining prostatic enlargement. Thus, in an effort to increase efficacy of treatment for BPH, clinical trials are under way using new drugs, such as GI-198745 (Glaxo-Wellcome, Research Triangle Park, NC), PNU 157706 (Pharmacia & Upjohn, Peapack, NJ), FR146687 (Fujisawa, Osaka, Japan), and LY 320236 (Lilly, Indianapolis, IN), which inhibit both the type-1 and type-2 5alpha-reductase.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1999

Reduced progesterone metabolites are not critical for plus-maze performance of lactating female rats.

Lactation has been associated with anxiolysis in several tests of anxiety. These observations, considered together with observations that progesterone and its 5alpha-reduced metabolites are anxiolytic in cycling, nonlactating females, raised the question of whether the changes in anxiety-related behaviors that accompany lactation are driven by reduced progesterone metabolites. Lactating female rats were tested on the plus-maze on postpartum days 2 or 7, and demonstrated enhanced open-arm performance relative to cycling, nonlactating females. Hormonal analysis indicated that while serum levels of both progesterone and its 3alpha,5alpha-reduced metabolite were increased in lactating females, the turnover of progesterone to the metabolite was markedly reduced during lactation. Furthermore, treatment with a 5alpha-reductase inhibitor for 3 days prior to testing potentiated the open-arm performance in lactating females, implying that enhanced open-arm performance was not mediated by the reduction of progesterone or other steroids. Additionally, analysis of GABA(A) receptor function indicated that parturition and lactation did not alter the sensitivity of the receptor to GABA or to modulation by reduced steroids. The mechanisms driving enhanced plus-maze behavior in lactating females appear to differ from mechanisms identified in nonlactating females.

5-alpha Reductase Inhibitors↗
PubMed1998

The medical management of lower urinary tract symptoms and benign prostatic hyperplasia.

Prostatism is a widely used term assigned to the symptom complex of older men with voiding dysfunction. The cause of the syndrome has routinely been ascribed to an enlarged prostate. More recent thinking recognizes that many men with such symptoms do not, in fact, have prostate enlargement or benign prostatic hyperplasia (BPH) and that such symptoms are not a surrogate for BPH. Such recognition is essential if cost effective medical management of lower urinary tract symptoms (LUTS) is to be achieved. Prostate volume has emerged as a key factor in the selection of medical therapy of LUTS and BPH not only regarding symptom relief but also to the newer concept of the prevention of disease progression and the avoidance of future adverse events in those men with true BPH. In the United States, medical management is now first line therapy for LUTS. The proper selection of therapy based on the patient's individual pathophysiologic characteristics is now made possible by many new recent studies within the medical literature.

Adrenergic alpha-Antagonists↗
PubMed1999

Treatment changes in prostatic hyperplasia and cancer, including androgen deprivation therapy and radiotherapy.

Substantial and characteristic changes occur in the microscopic appearance and immunophenotype of the hyperplastic prostate and adenocarcinoma following androgen deprivation therapy and radiotherapy. These changes are rarely seen in untreated cancer, and in the authors' opinion, the combinations of features following therapy are sufficiently distinctive to warrant recognition. Pathologists must be aware of these distinct changes because of the reliance placed on nuclear and nucleolar size in the identification of prostate cancer, particularly in small specimens and lymph node metastases.

5-alpha Reductase Inhibitors↗
PubMed2003

Sexual function in patients treated for benign prostatic hyperplasia.

CONTEXT: What is the effect of different treatment options for benign prostatic hyperplasia (BPH) on sexual function or dysfunction? With increasing age, sexual dysfunction and BPH become more prevalent. Some treatments for BPH can affect sexual function. Different surgical treatments have different effects on sexual function depending on how much the internal involuntary sphincter is affected. The same is true for medical therapies, each class of drug having a unique affect on sexual function. STARTING POINT: In the past, many articles suggested a causal relation between BPH and sexual dysfunction. But a recent report by H Leliefeld and colleagues (BJU International 2002; 89: 208-13) confirms the idea that the relation is coincidental. Prospectively, these investigators examined patients at baseline and 9 months after various treatments for BPH with questionnaires on voiding symptoms, related complications, and sexual function. 84% of patients reported no change in sexual function. All treatments showed both improvement and deterioration in 3-14% and 0-16% of patients, respectively. As expected, age was the most important determinant of sexual function. In addition, the effect of severe irritative symptoms or the presence of urological comorbidity, such as bladder stones, increased the rate of sexual dysfunction. In this study, most patients underwent surgical therapy or watchful waiting while fewer had medical therapy. Too few patients had minimally invasive procedures to comment on their effect on sexual function. WHRE NEXT? Thus the relation between treatment of BPH (or watchful waiting) and sexual dysfunction is usually coincidental, unless symptoms become severe or complications (such as bladder stones or urinary retention) develop. More prospective studies are needed to assess the effect of BPH and its treatment on sexual function. Medical therapy is now more common than surgery in developed countries and treatment of BPH is commonly advocated for improvement in quality of life. Therefore any effects on sexual function become even more important. As minimally invasive surgical operations become more common, more data will be required for such interventions. The difficulty will be in keeping up with the rapidly evolving techniques of minimally invasive therapies.

Adult↗
PubMed2003

Prostate cancer epidemiology.

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.

Adult↗
PubMedDate not supplied

[Treatment of benign prostatic hypertrophy: present situation and future prospects].

Review article offering an up-to-date view and a forecast for the future evolution of a disease which over the last few years has been the subject of increasingly scientific thoroughness. It deals with the natural history of the disease and the application of basic knowledge from other fields. It establishes the importance of a therapeutic evaluation of the results obtained with alternative medical and surgical approaches in the management of this entity. This review of benign prostate hyperplasia analyses the present realities and the future perspectives of the disease. It includes the most important contributions from international consensus and recommendations, and evaluation of the impact of drug treatment, the discredit of alternative options, the contribution of basic sciences to the understanding of the development of prostate cancer and the future of surgical management (TUR) and its alternatives.

5-alpha Reductase Inhibitors↗
PubMed2003

The impact of prostate volume following neoadjuvant androgen deprivation on quality of life and voiding symptoms in patients undergoing permanent prostate brachytherapy.

OBJECTIVE: Patients with large prostate volumes undergoing interstitial brachytherapy (BT) are currently believed to have worse urinary symptoms and quality of life (QOL) following the implant. We sought to determine if data from patients treated with neoadjuvant androgen ablation followed by BT at our institution supported this notion using a cross-sectional study design. METHODS: From 14 March 1997 to 25 August 2000, 248 patients underwent neoadjuvant androgen ablation followed by BT monotherapy (BTM) or BT combined with external beam (BTC) for treatment of localized prostate cancer. FACT-G and AUASS questionnaires were mailed to all patients on 1 September 2001. Overall FACT-G scores along with the irritative (IAUA) and obstructive (OAUA) subscales of the AUASS were calculated for each patient. Prostate volume (one to two weeks prior to BT), number of seeds, and implant method (ultrasound or CT guided) were compared with the outcomes on the two validated instruments. All analyses were adjusted for time since procedure and patient age. RESULTS: 169 of 248 (68%) patients returned questionnaires. The median prostate volume was 37cc and number of seeds implanted was 95. Our data shows little correlation between total FACT-G or AUASS scores and volume of the prostate. Likewise, neither FACT-G nor IAUA scores appeared related to the number of seeds implanted. A correlation was seen when comparing number of seeds with OAUA scores, but this result appeared to be driven by the BTC group. Number of needles implanted did not appear to be related to total FACT-G scores. The number of needles inserted was related to both IAUA and OAUA scores in the BTC group, but not in BTM group. CONCLUSION: Quality of life and urinary function scores do not appear to be strongly related to pre-implant prostate volume or method of implantation and thus patients should not be dissuaded from considering neoadjuvant androgen ablation followed by BT solely due to prostate size.

Aged↗