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LE Magazine December 2004

Lower urinary tract symptoms and benign prostatic hyperplasia.
Benign prostatic hyperplasia (BPH) is an important cause of lower urinary tract symptoms (LUTS). However, many other causes, including smooth muscle dysfunction and neurological factors may contribute to these symptoms, and accurate diagnosis is imperative before invasive treatments are chosen. Careful recording of symptoms, giving emphasis on how they interfere with the patient’s quality of life, as well as the use of properly selected tests, constitutes the mainstay of making a correct diagnosis. Men with mild or moderate symptoms not experiencing complications are ideal candidates for medical treatment. For the rest with persistent symptoms or complications such as infection, bleeding, chronic retention or renal impairment further investigation and more invasive forms of treatment need to be considered. We review the patho-physiology of the disease, and current approaches and management of this common problem.

Minerva Urol Nefrol. 2004 Jun;56(2):109-22

Phytotherapy for benign prostatic hyperplasia.
OBJECTIVE: To systematically review the existing evidence regarding the efficacy and safety of phytotherapeutic compounds used to treat men with symptomatic benign prostatic hyperplasia (BPH). DESIGN: Randomized trials were identified searching MEDLINE (1966—1997), EMBASE, Phytodok, the Cochrane Library, bibliographies of identified trials and review articles, and contact with relevant authors and drug companies. The studies were included if men had symptomatic benign prostatic hyperplasia, the intervention was a phytotherapeutic preparation alone or combined, a control group received placebo or other pharmacologic therapies for BPH, and the treatment duration was at least 30 days. Key data were extracted independently by two investigators. RESULTS: A total of 44 studies of six phytotherapeutic agents (Serenoa repens, Hypoxis rooperi, Secale cereale, Pygeum africanum, Urtica dioica, Curcubita pepo) met inclusion criteria and were reviewed. Many studies did not report results in a method allowing meta-analysis. Serenoa repens, extracted from the saw palmetto, is the most widely used phytotherapeutic agent for BPH. A total of 18 trials involving 2939 men were reviewed. Compared with men receiving placebo, men taking Serenoa repens reported greater improvement of urinary tract symptoms and flow measures. Serenoa repens decreased nocturia (weighted mean difference (WMD) = -0.76 times per evening; 95% CI = -1.22 to -0.32; n = 10 studies) and improved peak urine flow (WMD = 1.93 ml s(-1); 95% CI = 0.72 to 3.14, n = 8 studies). Men treated with Serenoa repens rated greater improvement of their urinary tract symptoms versus men taking placebo (risk ratio of improvement = 1.72; 95% CI = 1.21 to 2.44, n = 8 studies). Improvement in symptoms of BPH was comparable to men receiving the finasteride. Hypoxis rooperi (n = 4 studies, 519 men) was also demonstrated to be effective in improving symptom scores and flow measures compared with placebo. For the two studies reporting the International Prostate Symptom Score, the WMD was -4.9 IPSS points (95% CI = -6.3 to -3.5, n = 2 studies) and the WMD for peak urine flow was 3.91 ml s(-1) (95% CI = 0.91 to 6.90, n = 4 studies). Secale cereale (n = 4 studies, 444 men) was found to modestly improve overall urological symptoms. Pygeum africanum (n = 17 studies, 900 men) may be a useful treatment option for BPH. However, review of the literature has found inadequate reporting of outcomes which currently limit the ability to estimate its safety and efficacy. The studies involving Urtica dioica and Curcubita pepo are limited although these agents may be effective combined with other plant extracts such as Serenoa and Pygeum. Adverse events due to phytotherapies were reported to be generally mild and infrequent. CONCLUSIONS: Randomized studies of Serenoa repens, alone or in combination with other plant extracts, have provided the strongest evidence for efficacy and tolerability in treatment of BPH in comparison with other phytotherapies. Serenoa repens appears to be a useful option for improving lower urinary tract symptoms and flow measures. Hypoxis rooperi and Secale cereale also appear to improve BPH symptoms although the evidence is less strong for these products. Pygeum africanum has been studied extensively but inadequate reporting of outcomes limits the ability to conclusively recommend it. There is no convincing evidence supporting the use of Urtica dioica or Curcubita pepo alone for treatment of BPH. Overall, phytotherapies are less costly, well tolerated and adverse events are generally mild and infrequent. Future randomized controlled trials using standardized preparations of phytotherapeutic agents with longer study durations are needed to determine their long-term effectiveness in the treatment of BPH.

Public Health Nutr. 2000 Dec;3(4A):459-72

Fatty fish consumption and risk of prostate cancer.
Consumption of fatty fish might reduce the risk of prostate cancer, although epidemiological studies of fish consumption are rare. We studied the association between fish consumption and prostate cancer in a population-based prospective cohort of 6272 Swedish men. During 30 years of follow-up, men who ate no fish had a two-fold to three-fold higher frequency of prostate cancer than those who ate moderate or high amounts did. Our results suggest that fish consumption could be associated with decreased risk of prostate cancer.

Lancet. 2001 Jun 2;357(9270):1764-6

Effects of tomato sauce consumption on apoptotic cell death in prostate benign hyperplasia and carcinoma.
Population studies have suggested that lycopene, which is mostly found in tomato and tomato products, may reduce the risk of prostate cancer. We previously found that tomato sauce consumption prior to prostatectomy for prostate cancer decreased serum prostate specific antigen, decreased oxidative DNA damage, and increased lycopene concentrations in prostate tissue (Chen et al., 2001). Here, we extended those investigations to determine whether apoptotic cell death and associated Bcl-2 and Bax proteins were modulated by tomato sauce intervention. Thirty-two patients diagnosed by biopsy with prostate carcinoma were given tomato sauce pasta entrees (30 mg lycopene/day) for 3 wk before prostatectomy. Thirty-four patients with prostate cancer who did not consume tomato sauce and underwent prostatectomy served as controls. When tumor areas with the most apoptotic cells were compared in the biopsy (before) and resected prostate tissue (after), tomato sauce consumption increased apoptotic cells in benign prostate hyperplasia (BPH) from 0.66 +/- 0.10% to 1.38 +/- 0.31% (P = 0.013) and in carcinomas from 0.84 +/- 0.13% to 2.76 +/- 0.58% (P = 0.0003). When comparable morphological areas were counted, apoptotic cell death in carcinomas increased significantly with treatment, from 0.84 +/- 0.13% to 1.17 +/- 0.19% (P = 0.028), and apoptotic cell death in BPH showed a tendency toward an increase from 0.66 +/- 0.10% to 1.20 +/- 0.32% (P = 0.20). When the values of apoptotic cells in BPH and carcinomas of patients who consume tomato sauce were compared with corresponding control lesions of the patients who did not consume tomato sauce in resected prostate tissue, the differences of values were not significant [BPH 1.38 +/- 0.31% vs. 1.14 +/- 0.32% (P = 0.97); carcinomas 2.76 +/- 0.58% vs. 1.91 +/- 0.32% (P = 0.24)]. Tomato sauce consumption did not affect Bcl-2 expression but decreased Bax expression in carcinomas. These data provide the first in vivo evidence that tomato sauce consumption may suppress the progression of the disease in a subset of patients with prostate cancer by increasing apoptotic cell death. However, because of the relatively small number of control and tomato sauce-supplemented patients and the variability in the values of apoptotic cells in BPH and carcinomas, a much larger number of patients needs to be examined to support the data generated in this study.

Nutr Cancer. 2003;47(1):40-7

Lower prostate cancer risk in men with elevated plasma lycopene levels: results of a prospective analysis.
Dietary consumption of the carotenoid lycopene (mostly from tomato products) has been associated with a lower risk of prostate cancer. Evidence relating other carotenoids, tocopherols, and retinol to prostate cancer risk has been equivocal. This prospective study was designed to examine the relationship between plasma concentrations of several major antioxidants and risk of prostate cancer. We conducted a nested case-control study using plasma samples obtained in 1982 from healthy men enrolled in the Physicians’ Health Study, a randomized, placebo-controlled trial of aspirin and beta-carotene. Subjects included 578 men who developed prostate cancer within 13 years of follow-up and 1294 age- and smoking status-matched controls. We quantified the five major plasma carotenoid peaks (alpha- and beta-carotene, beta-cryptoxanthin, lutein, and lycopene) plus alpha- and gamma-tocopherol and retinol using high-performance liquid chromatography. Results for plasma beta-carotene are reported separately. Odds ratios (ORs), 95% confidence intervals (Cls), and Ps for trend were calculated for each quintile of plasma antioxidant using logistic regression models that allowed for adjustment of potential confounders and estimation of effect modification by assignment to either active beta-carotene or placebo in the trial. Lycopene was the only antioxidant found at significantly lower mean levels in cases than in matched controls (P = 0.04 for all cases). The ORs for all prostate cancers declined slightly with increasing quintile of plasma lycopene (5th quintile OR = 0.75, 95% CI = 0.54-1.06; P, trend = 0.12); there was a stronger inverse association for aggressive prostate cancers (5th quintile OR = 0.56, 95% CI = 0.34-0.91; P, trend = 0.05). In the placebo group, plasma lycopene was very strongly related to lower prostate cancer risk (5th quintile OR = 0.40; P, trend = 0.006 for aggressive cancer), whereas there was no evidence for a trend among those assigned to beta-carotene supplements. However, in the beta-carotene group, prostate cancer risk was reduced in each lycopene quintile relative to men with low lycopene and placebo. The only other notable association was a reduced risk of aggressive cancer with higher alpha-tocopherol levels that was not statistically significant. None of the associations for lycopene were confounded by age, smoking, body mass index, exercise, alcohol, multivitamin use, or plasma total cholesterol level. These results concur with a recent prospective dietary analysis, which identified lycopene as the carotenoid with the clearest inverse relation to the development of prostate cancer. The inverse association was particularly apparent for aggressive cancer and for men not consuming beta-carotene supplements. For men with low lycopene, beta-carotene supplements were associated with risk reductions comparable to those observed with high lycopene. These data provide further evidence that increased consumption of tomato products and other lycopene-containing foods might reduce the occurrence or progression of prostate cancer.

Cancer Res. 1999 Mar 15;59(6):1225-30

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