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PubMed2005

Selecting therapy for maintaining sexual function in patients with benign prostatic hyperplasia.

In the first of these mini-reviews the selection of therapy for the maintenance of sexual function in patients with BPH is outlined, along with an explanation of how altered regulation of neurotransmitters, especially noradrenaline, may underlie the syndrome of LUTS and sexual dysfunction. Other mini-reviews outline the current status of robotic surgery to treat renal and adrenal disorders, and its future applications, and the potential use of the nitric oxide/cGMP pathway as a potential target to treat BOO associated with benign prostatic enlargement. Finally, the capacity to be creative in academic departments is extolled as a core property of academicians, and its surfacing described as having the potential to revitalize individuals and departments.

5-alpha Reductase Inhibitors↗
PubMed2005

The impact of medical therapy on surgery for benign prostatic hyperplasia: a study comparing changes in a decade (1992-2002).

OBJECTIVES: To compare the clinical profile (age, comorbidities, symptom severity, and incidence of acute urinary retention, AUR), the type and duration of medical treatment, and indications for surgery of patients undergoing surgery for benign prostatic hyperplasia (BPH) in 1992 and 2002 at one centre. PATIENTS AND METHODS: In this single-centre, retrospective, cross-sectional observational study, the medical history of all patients who had surgery for BPH in the first semester of 1992 (85) and 2002 (70) was reviewed. The preoperative clinical profile was determined by assessing age, main comorbidities, prostatic volume, maximum urinary flow rate and symptom severity. The type and duration of pharmacology for BPH was evaluated from the medical history and telephone contact with the patients. Indications for surgery, the method of operation and the weight of removed tissue (open adenectomy) or the volume of the resected tissue (transurethral resection) were obtained from the patients' records and compared. Surgical complications in both groups were assessed, as was the average stay in hospital. RESULTS: In our institution, surgery for BPH decreased by 17.6% in the decade, with patients having surgery when older, at a mean (sd) of 69.1 (8.57) vs 72.3 (7.59) years, i.e. 3.1 years older (P = 0.028), but with similar comorbidities. Reasons for surgery in 1992/2002, respectively, were AUR in 41/37%, and symptoms worsening in 48/51%. The few cases of haematuria and bladder stone were similarly distributed in both groups. Pharmacology for BPH was prescribed in 46% of patients in 1992, phytotherapy being the most common (89%), whereas in 2002, 82% (P < 0.01) were treated, most of them with alpha-adrenergic antagonists (79%). Open surgery was indicated in 18.8% of patients in 1992 (mean adenoma weight 73.8 g, sd 37.12) and in 28.6% in 2002 (79.8 g, sd 35.41; P = 0.625). The mean (sd) hospital stay was 8.9 (4.06) vs 5.0 (1.22) days in 1992 and 2002, respectively (P < 0.01) for transurethral resection, and 14.1 (5.74) vs 8.7 (4.83) for open adenectomy (P = 0.013). The complication rate was similar for both groups. CONCLUSIONS: Compared with 1992, fewer patients with BPH have surgery, when older and after receiving medical treatment for longer. The indications for surgery are similar. Significantly more patients had open surgery, perhaps because the progressive increase in prostate volume was not affected by the medical therapy used predominantly during this decade.

5-alpha Reductase Inhibitors↗
PubMed1993

Hormonal chemoprevention of cancer in women.

The use of oral contraceptives in the United States during the past three decades has led to a dramatic decline in the incidence of cancers of the ovary and endometrium. The magnitude of these declines was predictable both from epidemiologic data and from the biologic effects of oral contraceptives on these tissues. Although the incidence of breast cancer has not been substantially affected by current oral contraceptives, it may be possible to develop alternative forms of contraception that provide protection against all three cancers. The major goal of hormonal chemoprevention of cancer is to reduce cell proliferation in the relevant epithelial tissue. New chemopreventive agents such as tamoxifen exemplify the application of this principle.

5-alpha Reductase Inhibitors↗
PubMed2004

Inhibition of 5alpha-reductase blocks prostate effects of testosterone without blocking anabolic effects.

We studied the effect of the 5alpha-reductase inhibitor MK-434 on responses to testosterone (T) in orchiectomized (ORX) male Brown Norway (BN) rats aged 13 mo. At 4 wk after ORX or sham surgery, a second surgery was performed to implant pellets delivering 1 mg T/day or placebo pellets. During the second 4 wk of the study, rats received injections of MK-434 (0.75 mg/day) or vehicle injections. Treatment with T elevated serum T to 75% above that for sham animals (P = 0.002) and did not affect serum dihydrotestosterone (DHT) or serum estradiol. T treatment also caused an elevation of prostate T and a marked elevation of prostate DHT. During the second half of the study, ORX rats lost an average of 18.86 +/- 4.62 g body wt. T completely prevented weight loss, and the effect was not inhibited by MK-434 (P < 0.001). ORX produced a nonsignificant trend toward a small (5%) decrease in the mass of the gastrocnemius muscle (P = 0.0819). This trend was also reversed by T, and the effect of T was not blocked by MK-434. T caused a significant 16% decrease in subcutaneous fat that was not blocked by MK-434 (P < 0.05). Finally, T caused a 65% decrease in urine excretion of deoxypyridinoline, a marker of bone resorption, and again the effect was not blocked by MK-434 (P < 0.0001). In contrast, T caused a greater than fivefold increase in prostate mass, and the effect was almost completely blocked by MK-434 (P < 0.0001). This study demonstrates that 5alpha-reductase inhibitors may block the undesirable effects of T on the prostate, without blocking the desirable anabolic effects of T on muscle, bone, and fat.

Androgens↗
PubMed2006

Obesity, diabetes, and risk of prostate cancer: results from the prostate cancer prevention trial.

Studies on the relationship between obesity and prostate cancer incidence are inconsistent. In part, this inconsistency may be due to a differential effect of obesity on low-grade and high-grade cancer or confounding of the association of obesity with prostate cancer risk by diabetes. We investigated the associations of obesity and diabetes with low-grade and high-grade prostate cancer risk. Data were from 10,258 participants (1,936 prostate cancers) in the Prostate Cancer Prevention Trial who all had cancer presence or absence determined by prostate biopsy. Multiple logistic regression was used to model the risk of total prostate cancer, and polytomous logistic regression was used to model the risk of low-grade and high-grade prostate cancer. Compared with men with body mass index < 25, obese men (body mass index > or =30) had an 18% [odds ratio (OR), 0.82; 95% confidence interval (95% CI), 0.69-0.98] decreased risk of low-grade prostate cancer (Gleason <7) and a 29% (OR, 1.29; 95% CI, 1.01-1.67) increased risk of high-grade prostate cancer (Gleason > or =7) or, alternatively, a 78% (OR, 1.78; 95% CI, 1.10-2.87) increased risk defining high-grade cancer as Gleason sum 8 to 10. Diabetes was associated with a 47% (OR, 0.53; 95% CI, 0.34-0.83) reduced risk of low-grade prostate cancer and a 28% (OR, 0.72; 95% CI, 0.55-0.94) reduced risk of high-grade prostate cancer. Associations of obesity or diabetes with cancer risk were not substantially changed by mutually statistical controlling for each other. Obesity increases the risk of high-grade but decreases the risk of low-grade prostate cancer, and this relationship is independent of the lower risk for prostate cancer among men with diabetes.

Adenocarcinoma↗
PubMed1998

Other antiandrogens.

Various substances of steroidal or nonsteroidal structure may serve as an alternative for the antiandrogenic treatment of acne. Compounds with antiandrogenic properties like cimetidine or ketoconazole are rarely administered for acne due to their weak effects. In contrast, spironolactone is an effective antiandrogen that shows good treatment effects in hirsutism and acne. Side effects occur frequently and are dose dependent. Isotretinoin--the most effective agent in acne therapy--has been under discussion for additional antiandrogenic properties for years. At present there is additional evidence for the antiandrogenic effects of isotretinoin. Regarding substances acting on both levels, androgen receptor binding and 5 alpha-reductase inhibition, the question is raised whether the term 'antiandrogen' should be amplified by including the 5 alpha-reductase inhibitors. This would pay tribute to the biological aspect of antiandrogenicity that takes into account not only the mode of action but also the effects of the substance. Under this aspect type 1 5 alpha-reductase inhibitors may gain attention in the future.

Acne Vulgaris↗
PubMed2001

Lower urinary tract symptoms: what are the implications for the patients?

Patients with lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH) complain about symptoms such as weak stream, dribbling, intermittency, frequency, nocturia and urgency. To effectively manage these symptoms, it is important to better understand the epidemiology and/or the bothersomeness of these symptoms, the impact of the symptoms on the patient's quality of life and life style, when and why patients seek medical advice and the subsequent management of LUTS/BPH in clinical practice. This paper gives an overview of these issues considering 3 recently conducted European surveys. Although voiding symptoms are more frequent in patients with LUTS/BPH, storage symptoms, such as frequency, urgency, nocturia and urge incontinence, seem to be more bothersome to the patients. LUTS seem to have a negative impact on the patient's quality of life and sexuality and to interfere strongly with daily life activities. With regard to sexuality, interference with the patient's overall sex life and erection problems is experienced as much more bothersome than ejaculation problems. After the initial symptoms, most patients postpone a visit to the physician and try to adjust their life style to self manage their symptoms. Eventually they seek medical advice because they are too much bothered by their LUTS. In Italy, medical therapy is the most frequently administered treatment option by urologists (57% of patients) followed by surgery (37% of patients). alpha(1)-Adrenoceptor antagonists are the predominant medical therapy prescribed (70% of all medically treated patients), particularly tamsulosin (35% of all medically treated patients). An interview with European urologists confirms that alpha(1)-adrenoceptor antagonists, especially newer uro-selective ones like tamsulosin, are a very appropriate initial treatment choice in the management of both voiding and storage LUTS.

Adrenergic alpha-Antagonists↗
PubMed1996

Healthcare resources should be targeted to chemoprevention: the argument against.

Chemoprevention of prostate cancer is an attractive idea that appeals to many struggling with the treatment of this disease. Many details inherent in any preventive strategy must be considered before embarking on this course, no matter how seductive it may appear. Critical issues of effectiveness, cost, difficulties in implementation, side effects, duration of the preventive cycle, and public acceptance may thwart prevention of prostate cancer from being implemented in the near future.

Anticarcinogenic Agents↗
PubMed2005

Bayesian analysis of multicentre trial outcomes.

Bayesian methods provide flexibility in the analysis of data from multicentre trials that would be difficult to achieve by other means. This paper illustrates some useful applications of Bayesian methods to the analysis of multicentre trials, with emphasis on insights that would be difficult to obtain using conventional frequentist methods. Two trials provide data for illustration: a large multicentre trial comparing two doses of a drug with placebo with respect to an essentially continuous measurement for which the original analysis revealed a significant treatment by centre effect, and a large multicentre trial with intraclass correlation induced by a categorical outcome of up to four episodes of heartburn reported by individual patients. The data from both trials had been analysed previously using conventional frequentist methods. Both sets of data were reanalysed using Bayesian and empirical Bayesian methods; all of the analyses provided the same conclusions for the key questions regarding treatment differences. The Bayesian methods provided some insights useful for model checking and also provided a way to explore some important quantitative aspects about the magnitude of treatment effects.

Antacids↗
PubMed1990

The effect of the steroidal androgen receptor antagonist, Win 49,596, on the prostate and testis of beagle dogs.

The effect of the steroidal androgen receptor antagonist Win 49,596 on the prostate and testis was studied in beagle dogs and was compared to the effects of the nonsteroidal androgen receptor antagonist ICI 176,334 and the steroidal 5 alpha-reductase inhibitor MK-906. Win 49,596 was shown to bind to the androgen receptor from normal canine prostate with a Ki of 2.2 microM. After 16 weeks of treatment, prostate size, as estimated by transrectal ultrasonography, was unchanged in intact controls and was 26% of the initial size in castrate controls. Oral doses of Win 49,596 from 0.625-40 mg/kg.day for 16 weeks caused dose-dependent prostatic regression and a dose-related increase in both the incidence and severity of glandular atrophy of the prostate. Prostatic secretory function was also inhibited by Win 49,596 treatment. The effects of Win 49,596 at 40 mg/kg.day on prostatic weight, total DNA, histomorphology, and secretory function were similar to those of castration, while the effects of Win 49,596 at 10 mg/kg.day were similar to those of ICI 176,334 at 0.25 mg/kg.day and MK-906 at 1.0 mg/kg.day. No effects on testicular weight, daily sperm production, or spermatogenesis were observed; however, mild Leydig cell hyperplasia was observed in two dogs treated with 40 mg/kg.day Win 49,596. In addition, at 10 and 40 mg/kg.day Win 49,596, moderate but variable increases in serum testosterone levels were observed. In summary, Win 49,596 caused regression of the hypertrophic canine prostate without effects on spermatogenesis and/or sexual function, supporting its possible use in the treatment of human benign prostatic hypertrophy/hyperplasia.

5-alpha Reductase Inhibitors↗