Alcohol Found to Lessen Risk for Enlarged Prostate


Risk is 35 percent lower for men who drink 36 grams or more of alcohol per day

27 sept 2009-- A man's risk of developing benign prostatic hyperplasia (BHP) decreases as his consumption of alcohol increases, but not the risk of lower urinary tract symptoms (LUTS), according to a meta-analysis reported in the October issue of the Journal of Urology.

J. Kellogg Parsons, M.D., of the University of California San Diego, and colleagues screened 463 articles on alcohol intake, BHP and LUTS, and fully reviewed 33 articles before performing meta-analyses of 19 articles. The reviewers pooled data to assess the risk for BHP and LUTS for different levels of alcohol consumption.

The researchers calculated BHP risk in six strata defined by grams of alcohol per day: up to 5 gm/d, up to 12 gm/d, up to 15 gm/d, up to 24 gm/d, up to 36 gm/d, and more than 36 gm/d. Alcohol consumption was associated with a significant or marginally significant decrease in BHP risk for all six strata, with alcohol consumption of 36 gm or more daily associated with a 35 percent decrease in BHP risk compared to no alcohol consumption (odds ratio, 0.65). However, three of four studies that had a primary outcome of LUTS showed a non-significant trend toward increased likelihood of LUTS with increased alcohol consumption.

"Alcohol consumption is associated with a decreased likelihood of BPH but not of LUTS. Further studies are needed to determine the mechanisms by which alcohol modifies the risk of BPH," the authors write.

One study author reported financial relationships with two pharmaceutical companies.

Abstract
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Enlarged prostates: The choice of treatment needs careful consideration

There are many options now for managing prostate symptoms, but new surgical techniques are often over-promoted

19 oct 2008--In the last few years, the treatment options for prostate problems have expanded. The German Institute for Quality and Efficiency in Health Care (IQWiG) has assessed new treatments and warns that some new surgical techniques are being heavily promoted without first having been adequately evaluated.
Informed choices are essential
For many men, the symptoms of this condition are just annoying. But for some men, an enlarged prostate means going to the toilet so often that a good night's sleep has become a thing of the past. Most of the time the cause is an enlarged prostate, a condition doctors call "benign prostatic hyperplasia". One in five men in their 50s are affected - and the majority of men in their 70s will have symptoms.
The treatment choices have greatly expanded in recent years. However IQWiG's evaluation of the research raises questions about many surgical techniques. According to the Institute's Director, Professor Peter Sawicki, "Not everything that is new is necessarily an improvement. Better information is necessary to help men and their doctors weigh up the advantages and disadvantages of the various treatments."
To that end, IQWiG has published easy-to-understand summaries of the research in this area on IQWiG's website for the public, www.informedhealthonline.org. Included is information on managing prostate symptoms, medicines and surgical options as well as the stories of men who have used different treatments.
Most men with BPH symptoms will never need surgery
According to researchers' best estimates, about 3 out of every 10 men in Europe will handle their prostate symptoms without medication or surgery and perhaps only 1 in 10 will have surgery. The rest will use medications, including herbal medicines, if their symptoms become too troublesome.
"In Germany and other European countries, drugs called alpha blockers have taken over as the most common treatment choice for benign prostatic hyperplasia," said Professor Sawicki. "These drugs were originally developed to reduce high blood pressure, but prostate symptoms will also improve at least a little for 60% of the men who use them."
In analysing the research results for surgery, the Institute concluded that the original surgical procedures still have the best results. A few of the new surgical techniques appear to have good results - for example, possibly shortening the time needed in hospital. But more research is needed to confirm this. And most of the new techniques use equipment that has not yet been tested in enough trials.
"Prostate surgery can be very effective, but the adverse effects are a major concern for many men. Some of the newer techniques might have fewer adverse effects, but they may be so much less effective that the symptoms return, as bad as ever, within a couple of years," Professor Sawicki said.

AUA: New Therapies Show Promise for BPH

By Charles Bankhead
ORLANDO, 28 may 2008 -- Two new therapeutic strategies for benign prostatic hyperplasia (BPH) -- one oral, one injectable -- showed promise in clinical trials, investigators said here.
The vitamin D agonist elocalcitol significantly slowed prostate growth and improved urinary flow in a placebo-controlled dose-finding study reported at the American Urological Association meeting.
A second study found that a single intraprostatic injection of a PSA-activated protoxin significantly reduced prostate symptoms and volume in a small phase 1 clinical evaluation.
Elocalcitol is a nonhypercalcemic vitamin D agonist that demonstrated anti-inflammatory and antiproliferative activity in preclinical studies, said Francesco Montorsi, M.D., of the Universita Vita Salute San Raffaele in Milan, Italy. Preliminary clinical studies showed that elocalcitol arrests prostate growth and improves bladder function.
Clinical investigation continued in a dose-finding study involving 540 men with symptomatic BPH.
The patients were randomized to placebo or to one of three active therapies: elocalcitol 75 or 150 mcg or elocalcitol 150 mcg plus the alpha blocker tamsulosin (Flomax) at a dose of 0.4 mg.
Treatment continued for six months, and the primary endpoint was the percentage change in total prostate volume from baseline.
All three active-therapy groups did significantly better compared with placebo, which had a mean increase in prostate volume of 3.52%.
Prostate volume increased by 1.52% with the 75 mcg dose of elocalcitol (P<0.0135), 0.54% with 150 mcg of elocalcitol (PP=0.0059).
"The rate of prostate growth in the placebo group was in line with published literature," Dr. Montorsi said. "The reduced rate of growth with elocalcitol shows that the drug can arrest prostate growth."
Prostate symptoms improved by five to six points on the International Prostate Symptom Scale and did not differ between groups. Similarly, maximum urinary flow (Qmax) improved by about 1 to 2 mL/sec in all four groups.
"The results seem to be comparable to those historically obtained with the 'gold standard' alpha-blockers," said Dr. Montorsi.
In a subgroup analysis of men with IPSS scores ≥12 and at least three urgency episodes daily at baseline, the 150 mcg dose of elocalcitol led to significant improvement (P<0.01) compared with placebo, as did combination therapy (P<0.04).
Adverse events occurred less frequently with elocalcitol monotherapy compared with placebo and slightly more often with the combination, but the differences were not significant.
In particular, elocalcitol did not adversely affect sexual function compared with placebo.
Explaining the second strategy, investigators in Canada and at Johns Hopkins presented data from 15 patients treated with PRX302, a modified bacterial protoxin injected into the prostate.
The modified protoxin (proaerolysin) is activated by PSA, resulting in the release of C-terminal inhibitory peptide and generation of active toxin, said Peter J. Pommerville, M.D., of Can-Med Clinical Research in Victoria, British Columbia.
"We believe the activated toxin bores small holes into cell membranes, allowing the cell contents to leak out and promoting apoptosis," Dr. Pommerville said in an interview. "The end result is a reduction in prostate volume."
In the phase I study, three patients each received one of five doses of PRX302. Using transrectal ultrasound guidance, investigators injected the protoxin transperineally into both prostatic lobes. Additionally, three or four deposits per injection were made in the transition zone along the urethra.
The baseline prostate volume averaged 45.3 cm3 and decreased to 37.7 cm3 at 90 days (P<0.01).
IPSS score decreased from a baseline mean of 19.1 to 9.4 at 90 days (P=0.015).
Quality-of-life score improved from a mean of 4.3 at baseline to 1.8 at 90 days (P<0.01).
"We hypothesize that the reduction in prostate mass reduces the pressure on the urethra, leading to a reduction in prostate symptoms," said Dr. Pommerville.
The protoxin was well tolerated; no grade 3-4 adverse events occurred during the study, he added. The most common adverse event was urinary frequency.
Dr. Montorsi disclosed relationships with GlaxoSmithKline, Pfizer, Bayer, Eli Lilly, Pierre Fabre, and AMS. Dr. Pommerville disclosed that he is an investigator for Protox Therapeutics.
Primary source: Journal of UrologySource reference:Montorsi F, et al "Elocalcitol in the treatment of BPH: a multicenter, randomized, placebo-controlled phase IIb clinical trial" J Urol 2008; 179(suppl): 700; Abstract 2035. Additional source: Journal of UrologySource reference: Pommerville PJ, et al "A PSA-activated protoxin (PRX302) administered transperineally to men with symptomatic benign prostatic hyperplasia is well tolerated and exhibits signs of activity" J Urol 2008; 179(suppl): 673; Abstract 1961.

For Men, Relief in Sight

By GERALD SECOR COUZENS
14 may 2008--MEN, the joke goes, spend the first half of their lives making money and the second making water. That is because after age 50 many men face an embarrassing problem called B.P.H., for benign prostatic hyperplasia. This slowly progressive enlargement of the prostate can make urination difficult or painful and send men trudging to the bathroom many times during the day and night.
Though bothersome, B.P.H. is not life threatening. Nor does it lead to cancer. When left untreated, however, B.P.H. can lead to serious health problems for some.
“My father used to be up 10 times a night and said it wasn’t a problem for him,” said Dr. Franklin C. Lowe, professor of urology at Columbia University College of Physicians and Surgeons. “However, he developed urinary tract infections annually because of his B.P.H. and almost died from sepsis one year. Surprisingly, his case is not unique.”
Many doctors are now urging men to become proactive earlier to prevent chronic problems in the future. Bladder stones, infections and bladder or kidney damage can arise and sometimes require surgery. Urological experts are beginning to rethink treatments, too, based on symptoms and how much a man is bothered by them.
“There is a big difference between having the symptoms and being bothered by the symptoms,” said Dr. Kevin T. McVary, professor of urology at the Feinberg School of Medicine at Northwestern University. “Some men go to the bathroom several times a night, get right back to sleep and are not bothered,” he said. Watchful waiting, or monitoring symptoms while holding off on medical or surgical treatments, is a reasonable plan for these men, he added. But for patients who have trouble getting back to sleep, “there are many effective options, and patients almost always end up with less bothersome symptoms once they choose to do something,” he said.
Although no drug offers a cure, “many men can be managed nicely with medical therapy,” Dr. Lowe said. The latest thinking is that combination therapy — taking both of the two main types of B.P.H. drugs — achieves maximum benefit. Alpha blockers like Flomax, Uroxatral, Hytrin and Cardura relax muscle fibers in the bladder and prostate. Other drugs like Proscar and Avodart, called 5-alpha-reductase inhibitors, shrink the prostate over 9 to 18 months. Once the drugs are stopped, however, symptoms typically recur. Researchers are also exploring the use of erectile dysfunction drugs for men with erection problems and B.P.H. as well as the antiwrinkle drug Botox.
There are also minimally invasive B.P.H. therapies that use heat, ultrasound, microwaves, low-frequency radio waves or lasers to hollow out the prostate’s core and relieve the pressure on the urethra that is reducing urine flow. These outpatient procedures have a long-lasting effect, although many men need an additional procedure within five years, and some even sooner.
“I tell patients, If you have to go through one procedure for your prostate, make sure it is one that will give long-lasting results,” Dr. Lowe said. He recommends the transurethral resection of the prostate. This “gold standard” surgery, performed under anesthesia, involves removing excess prostate tissue with an instrument inserted through the penis. It can offer relief for 10 years or more.
Robert H. Getzenberg, professor of urology at the Johns Hopkins Brady Urological Institute in Baltimore, notes that many men with B.P.H. are surprised to find that their urinary symptoms persist even after cancer surgery to remove the prostate. “People used to think that B.P.H. was just a disease of the prostate, and that’s not entirely true,” he said. “That’s because the prostate is only one component of B.P.H. The bladder, as we have found out, is another.”
Over time, he adds, the bladder may respond to changes in urinary patterns and pressure by becoming thicker and less resilient. When that occurs, a man feels as if he has to urinate more often, and the prostate problem has become a bladder issue.
Dr. Getzenberg believes there is more than one type of B.P.H., and that each requires different treatment. “There is the common B.P.H. found in most men as they age,” he said. “Urinary symptoms are mild and less likely to lead to bladder and other urinary tract damage.” A more severe form of B.P.H. is not always benign. “It’s highly symptomatic and has increased risk of damage to the bladder,” he added.
Genetic tests may eventually give men answers that will lead to better treatment of their condition. “If we can differentiate men into different groups, we can treat this disease more efficiently and effectively,” Dr. Getzenberg said. “This will allow us to intervene much earlier in the disease process.”

Dutasteride/Tamsulosin May Be Helpful for Benign Prostatic Hyperplasia

Laurie Barclay
December 28, 2007 — In men with moderate to severe lower urinary tract symptoms (LUTS) and prostate enlargement (≥ 30 cc) from benign prostatic hyperplasia (BPH), combination therapy with tamsulosin and dutasteride provided significantly greater benefit vs tamsulosin or dutasteride monotherapy, according to the 2-year results from the Combination of Avodart and Tamsulosin (CombAT) study reported in the February issue of the Journal of Urology.
"The aim of the ongoing CombAT study is to investigate whether combination therapy with dutasteride and the alpha-blocker tamsulosin is more effective than either monotherapy alone for improving the symptoms and long-term clinical outcomes of AUR [acute urinary retention] and BPH related prostatic surgery in men with moderate to severe symptoms of BPH and a prostate volume of 30 cc or greater," write Claus G. Roehrborn, from the University of Texas Southwestern Medical Center in Dallas, Texas, and colleagues. "We report the results of analyses of the 2-year primary and secondary end points of LUTS, Qmax [peak urinary flow] and prostate volume, and further analyses of efficacy data as well as safety and tolerability outcomes."
In this ongoing, multicenter, double-blind, parallel group study, men 50 years or older with a clinical diagnosis of BPH and LUTS were randomized to receive 0.5 mg of dutasteride, 0.4 mg of tamsulosin, or the combination once daily for 4 years. Inclusion criteria were International Prostate Symptom Score (IPSS) of 12 points or greater, prostate volume 30 cc or greater, total serum prostate-specific antigen (PSA) of 1.5 ng/mL or greater to 10 ng/mL or less, and peak urinary flow greater than 5 to 15 mL per second or less with a minimum voided volume of 125 mL or greater.
LUTS were evaluated every 3 months, and peak urinary flow was evaluated every 6 months. The main outcome measure at 2 years was the change from baseline in IPSS.
Compared with monotherapy, combination therapy resulted in significantly greater improvements in LUTS vs dutasteride from month 3 and tamsulosin from month 9, and in BPH-related health status from months 3 and 12, respectively. From month 6, combination therapy was associated with a significantly greater improvement from baseline in peak urinary flow vs monotherapy dutasteride or tamsulosin monotherapies.
Compared with monotherapies, combination therapy was associated with a significant increase in drug-related adverse events. However, most of these did not necessitate stopping treatment.
"In men with moderate to severe lower urinary tract symptoms and prostate enlargement (≥ 30 cc) combination therapy provides a significantly greater degree of benefit than tamsulosin or dutasteride monotherapy," the study authors write.
A limitation of the CombAT study was the lack of a double placebo group, which could potentially exaggerate symptom response.
"Data from the remaining 2 years of the CombAT study will provide further information on the pattern of symptoms and long-term outcomes (AUR and the need for BPH related surgery) associated with combination therapy vs tamsulosin and dutasteride monotherapies," the study authors conclude.
GlaxoSmithKline supported this study. Some of the authors have disclosed various financial relationships with GlaxoSmithKline, Pfizer, Astellas, Merck, Indevus, Eli Lilly, and Bayer.
In an accompanying editorial comment, Steven A. Kaplan, from Weill Cornell Medical College of Cornell University in New York City, notes that one must be cautious not to overinterpret these findings. Nonetheless, he describes CombAT as "an important contribution to our evolving understanding of the management of LUTS."
"The 5-ARIs [5-alpha-reductase inhibitor] and specifically in this study dutasteride are widely accepted as the backbone of therapy because of their unparalleled [effect] on disease management and they are also highly effective for relieving symptoms in select patients," Dr. Kaplan writes. "The alpha-blockers probably do not work as effectively in large prostates as they do in smaller prostates. What remains indisputable is that prostate size and symptom type, ie storage vs voiding at baseline, will drive therapeutic choices and optimize outcomes."
J Urol. 2008;179:616-621. Published online December 19, 2007.

Pain meds may worsen symptoms of enlarged prostate

Fri Sep 21, 4:25 PM ET
Common painkillers like ibuprofen and naproxen may act as a double-edged sword when it comes to men's prostate function, according to a report in the Harvard Men's Health Watch.
Recent evidence suggests that drugs such as these, called nonsteroidal anti-inflammatory drugs (NSAID), may lower the risk of developing an enlarged prostate and worsen urinary symptoms in men who already have the condition.
Prostate enlargement, known as benign prostatic hyperplasia (BPH), is common among older men. The condition is unrelated to prostate cancer, but it does cause bothersome symptoms such as frequent urination and difficulty with emptying the bladder completely.
It's known that certain medications, most commonly cold and allergy remedies, can make BPH symptoms worse. Now, a large study in the Netherlands recently implicated NSAIDs as another cause of worsening BPH, according to the Harvard publication.
Using data from 5,900 men age 45 and older, researchers found that men using NSAIDs were twice as likely as non-users to develop acute urinary retention, a sudden inability to empty the bladder.
The findings stand in contrast with those from a recent U.S. study of more than 2,400 men with no history of urological problems. Those who regularly used NSAIDs were less likely to develop BPH.
The seemingly conflicting results may reflect two different actions of NSAIDs, according to the report.
In men who already have BPH, the painkillers may worsen urinary symptoms because they block production of chemicals called prostaglandins; the bladder produces prostaglandins to enhance contractions of surrounding muscles, and blocking this process may make it even harder for men with BPH to empty their bladders.
On the other hand, there's evidence that inflammation contributes to the development of BPH, so NSAIDs may help prevent the condition.
However, younger men should not start popping painkillers to the lower their risk of BPH, according to the Harvard publication. All men should use NSAIDs carefully, following the label directions unless a doctor tells them otherwise.
Men with BPH should pay attention to whether their symptoms increase when taking an NSAID. If this does happen, they should tell their doctor, and possibly switch to acetaminophen (Tylenol) for pain relief.
SOURCE: Harvard Men's Health Watch, September 2007.

AUA: ED Drugs May Have Role in Treatment of BPH

ANAHEIM, Calif., May 25 -- Treatments for erectile dysfunction may prove effective against benign prostatic hyperplasia and lower urinary tract symptoms, possibly because they share a common etiologic pathway.
Studies involving all three of the currently available type 5 phosphodiesterase (PDE5) inhibitors showed improvement in BPH and urinary symptoms, regardless of whether the patients had concomitant erectile dysfunction. The three studies, two from the U.S. and one from Germany, were reported at the American Urological Association meeting.
The data reinforce an emerging theoretical and scientific framework that posits a common pathway for development of erectile dysfunction, benign prostatic hyperplasia, and lower urinary tract symptoms, and, the research suggests, possibly overactive bladder, researchers said.
The larger of the two prospective, randomized trials was conducted by Kevin McVary, M.D., of Northwestern University, and colleagues. It involved 369 men who had erectile dysfunction and concomitant lower urinary tract symptoms.
The patients, whose mean age was 60, had about a six-year history of erectile dysfunction and a five-year history of BPH and lower urinary tract symptoms. They were randomized to placebo or to 50 mg of sildenafil (Viagra) taken nightly before bedtime or 1 hour before sexual activity.
Treatment continued for 12 weeks. The primary endpoints were change in the erectile function (EF) domain score of the International Index of Erectile Function, change in the International Prostate Symptom Score (IPSS), and change in maximum urinary flow (Qmax).
Overall, patients treated with sildenafil had a 6.32-point improvement in the IPSS compared to 1.93 for the placebo group (P<0.001). EF domain scores improved by an average of 9.17 in the sildenafil group and 1.86 in the placebo group (P<0.001). Qmax did not differ between groups at baseline or at the end of the study.
Stratification of the data by baseline severity showed that patients with severe (IPSS ≥20) lower urinary tract symptoms improved substantially more compared with placebo than did those with moderate (IPSS 8-19) symptoms (P=0.0619). Among men with severe symptoms at baseline (54% of the cohort), substantially more had mild (16% vs. 4%) or moderate (57% vs. 36%) symptoms compared with placebo at the end of the study, the researchers found.
"The improvement in IPSS correlated with the IIEF changes," said Dr. McVary said. "Patients with more severe symptoms had more improvement, in a sense because they have more room for change."
He noted, however, that the researchers were surprised to find that the improvement did not correspond with the flow rate. "Although we didn't have an active comparator, the improvement looks to be comparable to what we might expect when giving alpha-blockers or a five-alpha reductase inhibitor," he said.
Asked to speculate about the lack of correlation between symptom improvement and flow rate, Dr. McVary said he and his colleagues initially suspected a predominance of urgency symptoms as opposed to obstruction. However, the data showed that both types of symptoms improved to a similar degree.
With respect to potential mechanisms involved in the co-existence of lower urinary tract symptoms and erectile dysfunction and the lack of flow improvement, Dr. McVary said that a pelvic deficiency in nitric oxide remains a viable explanation.
Other possibilities, he said, include an effect on bladder compliance, modulation of potential PDE5 effects on sensory innervation, and perhaps a change in pelvic flow affecting ischemia.
German investigators prospectively evaluated vardenafil (Levitra) as treatment for BPH in a randomized placebo-controlled study involving 222 men with moderate or severe symptoms.
The patients were randomized to placebo or vardenafil 10 mg BID for eight weeks, and the primary endpoints were change in IPSS, UROLIFE (a BPH quality-of-life questionnaire), and the EF domain of the IIEF.
The mean baseline IPSS was 16.8 in both groups. At the end of the study, vardenafil patients had a mean improvement of 5.9 compared with 3.6 for the placebo group (P=0.0013), reported Christian Stief, M.D., of Ludwig-Maximilians University in Munich.
Vardenafil also led to significantly greater improvement in the IPSS subscales for obstructive symptoms (3.2 vs. 1.9, P=0.0081) and irritative symptoms (2.6 vs. 1.7, P=0.0017).
The vardenafil group had significantly greater improvement on the UROLIFE questionnaire (P<0.0001 compared to placebo) and in the subscales for activity and perceived sexual life. IIEF scores improved by an average of 7.5 with vardenafil and 1.5 with placebo (P=0.0001).
The third study, a post hoc analysis of 156 men with erectile dysfunction and concomitant lower urinary tract symptoms showed that tadalafil (Cialis) significantly improved erectile function compared to placebo after 12 weeks of randomized therapy, reported Marc C. Gittelman, M.D., of South Florida Medical Research in Aventura, and colleagues.
Patients randomized to tadalafil started treatment at 5 mg/day for six weeks, followed by dose escalation to 20 mg/day over an additional six weeks.
Baseline IIEF scores averaged 13 to 14 in the placebo and tadalafil groups. The data were stratified by baseline urinary symptom severity.
Among patients with moderate symptoms, the erectile function score had improved by 6.8 points with tadalafil at six weeks versus 0.8 with placebo. At 12 weeks the tadalafil patients had a mean improvement of 8.3 compared with 1.7 in the placebo group.
In patients with severe symptoms, the EF domain score improved by 4.5 with tadalafil after six weeks compared to no change in the placebo group. At 12 weeks tadalafil patients had a mean improvement of 6.7 in the EF score compared with 0.7 in the placebo patients.
For all comparisons, tadalafil demonstrated a significant advantage over placebo (P<0.001). The magnitude of the tadalafil benefit did not differ between patients with moderate or severe lower urinary tract symptoms.
Multiple lines of evidence suggest a common pathophysiology for erectile dysfunction and BPH/lower urinary tract symptoms, said Dr. Kaplan. Such findings point toward the attractive possibility of treating the conditions with a single agent.