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 Clinical Management Series
Natural Medicines in the Clinical Management of Benign Prostatic Hyperplasia
Alpha-Blockers | Antiproliferatives and Growth Inhibiting Supplements | Anti-inflammatory Supplements
Miscellaneous | The Bottom Line | References
 

Benign prostatic hyperplasia (BPH) is a very common problem in older men. The chance of prostate problems increases dramatically with age. By age 60, over HALF of men have some prostate enlargement. By age 70, 90% have prostate enlargement. About a third of men over age 50 develop symptoms due to prostate enlargement.11215,11216,11217

The prostate is normally a walnut-sized gland that produces seminal fluid. The prostate is affected by testosterone and estrogen. Both hormones contribute to increased levels of dihydrotestosterone (DHT). DHT increases prostatic cell proliferation and glandular size.

As men age, testosterone levels decrease and estrogen levels increase. Estrogen increases the number of DHT receptors in the prostate and also inhibits DHT metabolism.11215,11216,11288 These changes can lead to further enlargement of the prostate.

BPH involves hyperplasia (an increase in the number of cells) rather than hypertrophy (an increase in the size of cells). But for practical purposes, the terms are often used interchangeably. BPH symptoms are caused by an increase in the number of cells in the prostatic epithelium and surrounding tissues. The enlarging prostate blocks the urethra, resulting in urinary symptoms. However, surprisingly, there's not a strong relationship between prostate size and severity of symptoms.

Men often wonder if BPH increases their risk for prostate cancer. It does not. BPH adversely affects the quality rather than the quantity of a man's life.11215,11218

Nonetheless, BPH symptoms can be very troubling for some men. Urinary incontinence can be socially debilitating. Nocturia can decrease sleep quality and affect daytime performance.11215

Symptoms of Benign Prostatic Hyperplasia11215,11219
Voiding (Obstructive) Symptoms Storage (Irritative) Symptoms
Hesitancy Frequency
Intermittency (urinary stream stops and starts) Nocturia
Decreased force of stream Urgency
Abdominal straining Urge incontinence
Incomplete emptying  
Prolonged urination  
Post-micturition dribbling  

Treatment options for BPH consist of doing nothing, drug treatment with alpha-blockers and/or 5-alpha reductase inhibitors, or surgical treatment. Treatment decisions are based on the severity of symptoms and their effect on quality of life.11221

Commonly Used Conventional and Natural Medicines for Benign Prostatic Hyperplasia*
Alpha-Adrenergic Blockers
   Alfuzosin (Uroxatral)
   Doxazosin (Cardura)
   Prazosin (Minipress)
   Tamsulosin (Flomax)
   Terazosin (Hytrin)
5-Alpha Reductase Inhibitors
   Conventional Medicines
      Dutasteride (Avodart)
      Finasteride (Proscar)
   Natural Medicines
      Saw palmetto (Serenoa repens)a
Antiproliferative
   African wild potato (Hypoxis hemerocallidea)
   Beta-sitosterol
   Lycopene
   Pumpkin seed (Cucurbita pepo)
   Pygeum (Prunus africana)
   Red clover (Trifolium pratense)
   Soy (Glycine max)
   Stinging nettle root (Urtica dioica)
Anti-inflammatories
   Rye grass pollen (Secale cereale)b
Miscellaneous
   Buchu (Agathosma betulina)
   Fireweed (Epilobium angustifoliumi)
   Flaxseed oil (Linum usitatissimum)
   Garlic (Allium sativum)
   Prickly pear cactus (Opuntia ficus-indica)
   Uva-ursi (Arctostaphylos uva-ursi)
Nutrients
   Selenium
   Vitamin Ec
   Zinc
a may also have anti-inflammatory and antiproliferative effects
b may also have alpha1-blocking activity
c may also have antiproliferative effects
*Note: Many natural products are tried for benign prostatic hyperplasia, but very few have reliable evidence that they work. Inclusion in this list does NOT imply that these products are effective for benign prostatic hyperplasia.

 
 
 
Alpha-Blockersreturn to top 

The alpha-blockers are most effective for reducing symptoms of BPH. Therefore, they are often considered first line agents for rapid symptom relief.

5-alpha Reductase Inhibitors

The 5-apha reductase inhibitors such as finasteride (Proscar) and dutasteride (Avodart) are often added on when alpha-blockers alone don't provide adequate symptoms relief. These drugs actually help shrink prostate tissues, whereas the alpha-blockers do not.

For men who have a high risk of BPH progression, immediately starting combination treatment with a 5-alpha reductase inhibitor plus alpha-blocker is usually the best bet. These are men who are over 50 years of age, have low urine flow, high PSA levels, or have larger prostates.

For more information on using combination treatment, read the Pharmacist's Letter / Prescriber's Letter Detail-Document #180714.

Many men turn to natural products to prevent or treat BPH, often in combination with conventional treatment.11222,11223 Unlike many natural products used for other conditions, some products used for BPH are good evidence-based alternatives to conventional drugs. Some natural products for BPH might work similar to the 5-alpha reductase inhibitors.

Saw palmetto (Serenoa repens) is the best known and most widely used supplement for BPH. It has antiandrogenic, antiproliferative, and anti-inflammatory properties. Saw palmetto seems to have some effects similar to finasteride and dutasteride. They all inhibit 5-alpha reductase which reduces prostate growth by preventing the conversion of testosterone to dihydrotestosterone (DHT).6765,6769,6770,6773 However, saw palmetto is less potent than finasteride and dutasteride.

Saw palmetto does not reduce overall prostate size like finasteride...but saw palmetto does seem to shrink the inner prostatic epithelium.5093 Saw palmetto's activity appears to be prostate-specific. Saw palmetto might also slow prostate cell proliferation by inhibiting several growth factors and by stimulating the normal death of some prostate cells.6765,6769,6770

Saw palmetto also seems to inhibit lipoxygenase and cyclooxygenase (COX) enzymes. These enzymes may be involved in prostate inflammation. A saw palmetto extract seems to lower markers of prostatic inflammation such as tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta.6769,6779,11224

Most research suggests that saw palmetto provides mild to moderate improvement in many BPH symptoms...frequent urination, painful urination, hesitancy, urgency. Saw palmetto also decreases nocturia, improves peak and mean urine flow, and lowers residual urine volume in men with BPH.764,2732,6750,6751,6762,6764,6772,6773,6777,6778,8330,14275 Saw palmetto seems to be as effective as finasteride, and saw palmetto might be better tolerated.6424,14275 Saw palmetto doesn't seem to cause impotence as often as finasteride.764,6424,6762 Unlike finasteride, saw palmetto also doesn't reduce prostate-specific antigen (PSA) levels. Finasteride can reduce PSA levels making prostate cancer monitoring more difficult.2735,6771

Saw palmetto does not seem to be as effective as alpha1-adrenergic blockers such as prazosin or selective alpha1-blockers such as alfuzosin (Uroxatral) and tamsulosin (Flomax) for BPH symptom relief.6775,6776,8901 And saw palmetto doesn't work as quickly as alpha1-blockers. Saw palmetto treatment for 1-2 months is usually necessary before men feel improvement.2732,6750,6778 But there's some research suggesting that saw palmetto might be as effective as tamsulosin for symptom relief after 12 months of treatment.11243 Combining saw palmetto with a selective alpha1-blocker such as tamsulosin does not seem to relieve symptoms any better than an alpha1-blocker alone.6775,6776,8901

Although most research is positive, not all research has shown a beneficial effect.11314,14274 In a recent high quality study, saw palmetto was ineffective for reducing symptoms in men with moderate to severe symptoms of BPH after a year of treatment.14274 The reason for this inconsistent finding might be due to different outcome measures, product selection, or other factors.

Most clinical studies have used a specific extract of saw palmetto berry containing 80% to 90% fatty acids. Encourage patients who want to use saw palmetto to use a product that contains this type of formulation. It's similar to Super Saw Palmetto (Enzymatic Therapy), ProstaPro (PhytoPharmica), Standardized Saw Palmetto Extract (Nature's Way), and others.

Saw palmetto is generally well-tolerated and causes few significant side effects. Dizziness and gastrointestinal complaints such as nausea, vomiting, constipation, and diarrhea occasionally occur.6751,6762,11354 There is a single case report linking saw palmetto use with intraoperative hemorrhage, but episodes of bleeding or coagulation abnormalities have not been reported in clinical studies.8659 There is also one report of acute hepatitis and pancreatitis in a patient who took saw palmetto.14457 Symptoms resolved when the patient stopped taking the product...and emerged again when it was restarted; however, researchers did not analyze the product to rule-out possible contamination.

Tell men with BPH who want to try saw palmetto to get a urologic exam first to rule out more serious conditions such as prostate cancer. Explain that taking a saw palmetto extract 320 mg daily might relieve BPH symptoms about as well as the prescription drug Proscar for some patients. Tell patients that there is no reason to take saw palmetto to prevent BPH or to "maintain urinary health." There is no reliable evidence that it works for this purpose.

 
View brands containing:
-Saw palmetto
  Question #1
Which of the following is TRUE regarding the use of saw palmetto for BPH?
  •   Question #2
    Before starting saw palmetto, men should
  •   Question #3
    How should you advise a man who wants to take saw palmetto for his BPH symptoms?
  • Antiproliferatives and Growth Inhibiting Supplementsreturn to top 

    Pygeum (Prunus africana), also known as African plum tree, is often tried for BPH. It's used alone or in combination with saw palmetto or other natural products. It's thought to be helpful for BPH due to antiproliferative and anti-inflammatory effects.

    There's preliminary evidence that pygeum suppresses epithelial growth factor (EGF). This might help shrink prostate epithelial cells.11226 Pygeum might also inhibit other growth factors...basic fibroblast growth factor (bFGF)...insulin-like growth factor (IGF). Inhibiting these growth factors might decrease prostate tissue growth and hyperplasia.4301 Pygeum may also have anti-inflammatory activity...it decreases production of leukotrienes and other 5-lipoxygenase metabolites.10425,10426

    In clinical studies, pygeum decreases nocturia by 19%, increases peak urine flow by 23%, and reduces residual urine volume by 24% in men with BPH.3902,3903,3904,4302,6368,10425,10426

    Explain to men that taking pygeum extract will probably help for symptoms of BPH. But it's not known if it is any more effective than standard treatments. Pygeum is very well tolerated. The most common side effect is GI upset.10426

    If a patient wants to try it, recommend taking 75-200 mg/day of a lipophilic extract standardized to contain 14% triterpenes. This formulation has been used in clinical studies and is contained in the brand name product Tadenan (Solvay Pharma).

    Stinging nettle root (Urtica dioica) has a long history of use for treating BPH symptoms and is widely used in Germany. Stinging nettle seems to have an antiproliferative effect on prostatic cells in vitro.11227,11229 It might also decrease the effects of androgenic hormones.11228

    Most research with stinging nettle has evaluated products containing both stinging nettle and saw palmetto. Some evidence suggests that these combinations might reduce symptoms.6763 But contradictory evidence suggests no benefit. Additionally, it's not known if any benefit is due to the stinging nettle, saw palmetto, or both. There's no reliable evidence that stinging nettle alone is effective...or that the combination of stinging nettle plus saw palmetto is any better than saw palmetto alone.

    For now, don't recommend stinging nettle combo products. If a man wants to try a product for BPH symptoms, single-ingredient saw palmetto products as described above are the best bet.

    Beta-sitosterol is a plant's version of cholesterol. It's found in many foods and herbs used for BPH. Beta-sitosterol is thought to be beneficial for BPH patients because it seems to have antiproliferative effects on prostate tissue.11234

    Taking beta-sitosterol 60-130 mg/day significantly improves urinary symptoms. It increases maximum urinary flow and decreases the volume of urine left in the bladder. Like saw palmetto, beta-sitosterol does not affect prostate size.5327,5328,5329,7198

    Beta-sitosterol is also used to lower cholesterol. It is an ingredient in the cholesterol-lowering margarine Take Control. Take Control contains 1120 mg beta-sitosterol per tablespoon.

    Tell men, particularly those with elevated cholesterol, who are interested in beta-sitosterol for BPH that it is worth a try. Keep in mind that if beta-sitosterol margarine is used, other fat in the diet should be reduced accordingly to prevent weight gain.

    African wild potato (Hypoxis hemerocallidea) (also known as South African star grass), pumpkin seed (Cucurbita pepo), and soy (Glycine max) are plant-based sources of beta-sitosterol.

    Some evidence suggests that a specific African wild potato extract (Harzol, Azuprostat) decreases urinary symptoms and improves quality of life in men with BPH.5327,5328,7198 There is also some evidence that a pumpkin seed extract might reduce some symptoms of BPH when used alone, or combined with saw palmetto.6777,11231 These extracts are promising, but it's too soon to recommend them.

    Practice Pearl
    African wild potato might have a hypoglycemic effect.11236 Tell patients with diabetes to monitor their blood sugar closely if they use products containing African wild potato.

    Even though soy is a source of beta-sitosterol, so far, there's no reliable evidence that soy extracts are helpful for reducing BPH symptoms. But preliminary research suggests that another constituent in soy, genistein, which is an isoflavone, might inhibit growth of prostate cells. More evidence is needed before soy should be recommended for BPH.

    Like soy, red clover (Trifolium pratense) contains isoflavones. Red clover might relieve BPH symptoms by an anti-androgenic effect.11239 It seems to increase the natural death of prostate cells rather than decreasing cell proliferation.11240

    Preliminary clinical evidence shows that taking red clover isoflavones 40-80 mg/day might decrease nocturnal urinary frequency and improve quality of life in some men with BPH. However, red clover isoflavones do not seem to affect urine flow rate, prostate-specific antigen (PSA) values, or prostate size.6128 It is too soon to recommend it.

    Lycopene, is a carotenoid pigment of tomatoes and other red or pink fruits and vegetables. It is widely promoted for "prostate health." Lycopene does seem to reduce proliferation of prostatic epithelial cells and might decrease the risk of prostate cancer.2406,7772,7773,7895,11237,12878 But there's no credible evidence that lycopene supplements are beneficial for treating or preventing BPH. Don't recommend lycopene supplements for treating symptoms of BPH. For people who are interested in lycopene for general prostate health, suggest increasing intake of lycopene-containing foods, such as tomatoes and tomato-based sauces.

    Men might ask about vitamin E for prostate health. Preliminary research suggests that vitamin E might have an antiproliferative effect on BPH cells.11235 But there's no reliable evidence that taking vitamin E supplements can prevent or treat BPH symptoms.

    There's been some buzz about vitamin E possibly reducing the risk of developing prostate cancer. But the evidence is inconsistent and contradictory.3959,11289,11303,12872,12873,13036,13043,14135 Advise patients not to rely on vitamin E supplements for preventing or treating prostate disease.

    		 
    View brands containing:
    -Pygeum
    View brands containing:
    -Stinging nettle root
      Question #4
    Which of the following is most appropriate to recommend for a BPH patient?
  • View brands containing:
    -Beta-sitosterol
    View brands containing:
    -African wild potato
    -Pumpkin seed
    -Soy
      Question #5
    In addition to improving BPH symptoms, beta-sitosterol can
  •   Question #6
    Which of these is a plant source of beta-sitosterol content?
  • View brands containing:
    -Red clover
    -Lycopene
    -Vitamin E
    Anti-inflammatory Supplementsreturn to top 

    Rye grass pollen (Secale cereale) extract contains beta-sterols. It seems to relax urethral smooth muscle tone and increase bladder muscle contractility. It might affect alpha1-adrenergic receptors and relax both the internal and external bladder sphincter muscles.8176 It might also decrease inflammation by inhibiting the biosynthesis of prostaglandins and leukotrienes.5298

    Rye grass pollen extracts seem to improve BPH symptoms...frequency, nocturia, urgency, decreased urine flow rate, dribbling, and painful urination in men with mild to moderate BPH.5292,5293,5294 It may also decrease prostate size, improve urinary flow, and decrease residual urine volume. But not all research has shown effects on these more objective BPH measures.5292,8176,8520

    Rye grass pollen extract is sold as a prescription drug throughout Western Europe, Japan, Korea, and Argentina.8176 Tell patients that rye grass pollen extracts appear to be safe and effective when used for up to 6 months. For patients who decide to try rye grass pollen, recommend Cernilton. It's the brand of rye grass pollen extract used in most clinical studies.

    Practice Pearl
    Rye grass pollen extract is unlikely to cause allergic reactions in men with allergy to rye grass pollen. During the extraction process of the brand Cernilton, allergens are removed.5292 Allergic reactions to rye grass pollen extract have not been reported in clinical trials.8176

    		 
    View brands containing:
    -Rye grass pollen
      Question #7
    What should you tell a patient who is interested in trying rye grass pollen for BPH?
  • Miscellaneousreturn to top 

    Garlic is sometimes used for BPH. There is preliminary evidence that it might be helpful for improving urinary flow, decreasing urinary frequency, and other symptoms associated with BPH or prostate cancer, according to preliminary clinical research.10374 But it's too soon to recommend garlic for BPH.

    A variety of herbs including prickly pear cactus (Opuntia ficus-indica), fireweed (Epilobium angustifolium), buchu (Agathosma betulina), uva-ursi (Arctostaphylos uva-ursi), flaxseed oil (Linum usitatissimum) are used for BPH. But there's no reliable evidence that they are effective.

    Minerals such as selenium and zinc are sometimes promoted for prevention or treatment of BPH. But there are no reliable clinical trials showing that either selenium or zinc is beneficial for BPH. In fact, population research suggests that a diet high in zinc might increase the risk of BPH.6908

    Herbs and Supplements that Might Adversely Affect BPH11242
    Products with sympathomimetic effects may make urination more difficult. Sympathomimetics increase muscle tone of the prostate stroma, causing the prostate to contract around the urethra. They may also cause contraction of the internal bladder sphincter.
    Bitter orange Yohimbe
    Products with anticholinergic effects can also make urination more difficult. Anticholinergics decrease the ability of the bladder detrusor muscle to cause bladder contraction.
    Henbane Scopolia
    Jimson weed Wild lettuce
    Products with hormonal activity can accelerate prostate enlargement.
    Androstenediol Dehydroepiandrosterone (DHEA)
    Androstenedione Pregnenolone

    		 
    View brands containing:
    -Garlic
    -Prickly pear cactus
    -Fireweed
    -Buchu
    -Uva-ursi
    -Flaxseed oil
    -Selenium
    -Zinc
      Question #8
    A patient asks you to recommend a supplement for BPH. Which of the following supplements would be the most appropriate choice?
  • The Bottom Linereturn to top 

    Saw palmetto is perennially one of the best selling herbal products worldwide. It appears to be about as effective as Proscar for BPH symptoms. Unlike Proscar, saw palmetto doesn't usually cause sexual dysfunction and doesn't affect PSA levels. Alpha1-blockers seem to provide more symptom relief than saw palmetto and have a faster onset of action.

    Pygeum is also well-studied for BPH symptoms. As a single agent, it appears to decrease nocturia, increase urine flow, and decrease residual urine volume. But it hasn't been compared to conventional BPH drugs.

    Beta-sitosterol is a constituent of many herbal products for BPH. It hasn't been compared with conventional BPH drugs, but appears to reduce BPH symptoms. Beta-sitosterol as a supplement or as beta-sitosterol margarine is a good choice for men who have BPH and hypercholesterolemia.

    African wild potato appears to help BPH symptoms, most likely because of its high beta-sitosterol content. Preliminary research suggests it may lower blood glucose, but this hasn't been reported in clinical studies. Tell men with diabetes who try African wild potato to monitor blood sugar closely.

    Rye grass pollen extract also contains beta-sitosterol. There's good research to support its use. Whether it works as well as Proscar or alpha1-blockers is unknown. It's used widely as a prescription drug in Europe, Japan, and other countries.

    Stinging nettle and pumpkin seed are sometimes added to combination BPH products. But more evidence is needed before they can be recommended. There's no proof that supplements with these added ingredients are more effective.

    A lot of men with BPH are interested in isoflavones, such as those found in soy and red clover. Tell men that there's some preliminary research that looks promising, but it's too soon to recommend isoflavones for BPH.

    People may ask about supplements such as garlic, lycopene, vitamin E, selenium, and zinc. There's a lot a research going on to see if these supplements are useful for treating or preventing prostate cancer. Remind patients that BPH does not predispose men to prostate cancer. So far, there's no reliable clinical evidence that any of these supplements can prevent or treat BPH.

    Combination therapy with alpha1-antagonists and Proscar might work better than either drug alone.11289 But combining saw palmetto with conventional prostate drugs doesn't seem to improve effectiveness. It's not known if combining other supplements with convention drugs offers any additional benefit.

    For men who want to try natural medicines for treating BPH, recommend single-ingredient products such as saw palmetto, pygeum, or beta-sitosterol. Although there is not as much evidence, rye grass pollen extract will probably also help many men. Explain to men that patience is needed when using these products. Adequate doses for a trial of 1-2 months is usually needed before determining if there is significant symptom relief.

    		 
      
     
    Recommendation Chart for Natural Medicines Used for BPH *
    Benign Prostatic Hyperplasia
    Safety/EffectiveLikely
    Safe    		Possibly
    Safe    		Insufficient
    Evidence    		Possibly
    Unsafe    		Likely
    Unsafe    		Unsafe
    Effective      
    Likely
    Effective
    -Beta-sitosterol
    -Pygeum
    -Saw palmetto
         		     
    Possibly
    Effective
    -Rye grass pollen
     
    -African wild potato
    -Pumpkin seed
         		    
    Insufficient
    Evidence
    -Garlic
    -Selenium
    -Soy
    -Vitamin E
    -Zinc
     
    -Buchu
    -Fireweed
    -Flaxseed oil
    -Lycopene
    -Prickly pear cactus
    -Red clover
    -Stinging nettle
    -Uva-ursi
         		    
    Possibly
    Ineffective    		      
    Likely
    Ineffective    		      
    Ineffective      
     KEY:
     Consider recommending this product.
     Don't recommend using this product.
     Recommend against using this product.

    * These proposed recommendations are based solely on the Safety and Effectiveness Ratings contained in Natural Medicines Comprehensive Database. This assumes use of high-quality, uncontaminated products and the use of typical doses. Keep in mind that some products are never appropriate for some patients due to concomitant disease states, potential drug interactions, or other clinical factors. Use your clinical judgment before recommending any product.

    References return to top
    764Gerber GS, Zagaja GP, Bales GT, et al. Saw palmetto (Serenoa repens) in men with lower urinary tract symptoms: effects on urodynamic parameters and voiding symptoms. Urol 1998;51:1003-7.
    2406Giovannucci E, Ascherio A, Rimm EB, et al. Intake of carotenoids and retinol in relation to risk of prostate cancer. J Natl Cancer Inst 1995;87:1767-76.
    2732Wilt TJ, Ishani A, Stark G, et al. Saw palmetto extracts for treatment of benign prostatic hyperplasia: a systematic review. JAMA 1998;280:1604-9.
    2735Marks LS, Tyler VE. Saw palmetto extract: newest (and oldest) treatment alternative for men with symptomatic benign prostatic hyperplasia. Urology 1999;53:457-61.
    3902Barlet A, Albrecht J, Aubert A, et al. [Efficacy of Pygeum africanum extract in the medical therapy of urination disorders due to benign prostatic hyperplasia: evaluation of objective and subjective parameters. A placebo-controlled, double-blind, multicenter study]. [Article in German]. Wien Klin Wochenschr 1990;102:667-73.
    3903Breza J, Dzurny O, Borowka A, et al. Efficacy and acceptability of tadenan (Pygeum africanum extract) in the treatment of benign prostatic hyperplasia (BPH): a multicentre trial in central Europe. Curr Med Res Opin 1998;14:127-39.
    3904Dufour B, Choquenet C, Revol M, et al. Controlled study of the effects of Pygeum africanum extract on the functional symptoms of prostatic adenoma. Ann Urol (Paris) 1984;18:193-5.
    3959Heinonen OP, Albanes D, Virtamo J, et al. Prostate cancer and supplementation with alpha-tocopherol and beta-carotene: incidence and mortality in a controlled trial. J Natl Cancer Inst 1998;90:440-6.
    4301Yablonsky F, Nicolas V, Riffaud JP, Bellamy F. Antiproliferative effect of Pygeum africanum extract on rat prostatic fibroblasts. J Urol 1997;157:2381-7.
    4302Andro MC, Riffaud JP. Pygeum africanum extract for the treatment of patients with benign prostatic hyperplasia. A review of 25 years of published experience. Curr Ther Res 1995;56:796-817.
    5093Marks L, Partin AW, Epstein JI, et al. Effects of a saw palmetto herbal blend in men with symptomatic benign prostatic hyperplasia. J Urol 2000;163:1451-6.
    5292Buck AC, Cox R, Rees RW, et al. Treatment of outflow tract obstruction due to benign prostatic hyperplasia with the pollen extract, cernilton. A double-blind, placebo-controlled study. Br J Urol 1990;66:398-404.
    5293Rugendorff EW, Weidner W, Ebeling L, Buck AC. Results of treatment with pollen extract (Cernilton N) in chronic prostatitis and prostatodynia. Br J Urol 1993;71:433-8.
    5294Yasumoto R, Kawanishi H, Tsujino T, et al. Clinical evaluation of long-term treatment using cernitin pollen extract in patients with benign prostatic hyperplasia. Clin Ther 1995;17:82-7.
    5298Loschen G, Ebeling L. [Inhibition of arachidonic acid cascade by extract of rye pollen]. [Article in German]. Arzneimittelforschung 1991;41:162-7.
    5327Berges RR, Windeler J, Trampisch HJ, et al. Randomised, placebo-controlled, double-blind clinical trial of beta-sitosterol in patients with benign prostatic hyperplasia. Beta-sitosterol Study Group. Lancet 1995;345:1529-32.
    5328Klippel KF, Hiltl DM, Schipp B. A multicentric, placebo-controlled, double-blind clinical trial of beta-sitosterol (phytosterol) for the treatment of benign prostatic hyperplasia. Br J Urol 1997;80:427-32.
    5329Wilt TJ, MacDonald R, Ishani A. beta-sitosterol for the treatment of benign prostatic hyperplasia: a systematic review. BJU Int 1999;83:976-83.
    6128Gerber G, Lowe FC, Spigelman S. The use of a standardized extract of red clover isoflavones for the alleviation of BPH symptoms. Endocrine Soc 82nd Ann Mtg, Toronto, CAN 2000;Jun 21-4:abstract 2359.
    6368Chatelain C, Autet W, Brackman F. Comparison of once and twice daily dosage forms of Pygeum africanum extract in patients with benign prostatic hyperplasia: a randomized, double-blind study, with long-term open label extension. Urology 1999;54:473-8.
    6424Carraro JC, Raynaud JP, Koch G, et al. Comparison of phytotherapy (Permixon) with finasteride in the treatment of benign prostate hyperplasia: a randomized international study of 1,098 patients. Prostate 1996;29:231-40.
    6750Champault G, Patel JC, Bonnard AM. A double-blind trial of an extract of the plant Serenoa repens in benign prostatic hyperplasia. Br J Clin Pharmacol 1984;18:461-2.
    6751Braeckman J. The extract of serenoa repens in the treatment of benign prostatic hyperplasia: a multicenter open study. Curr Ther Res 1994;55:776-85.
    6762Wilt T, Ishani A, Stark G, et al. Serenoa repens for benign prostatic hyperplasia. Cochrane Database Syst Rev. 2000;(2):CD001423.
    6763Sokeland J. Combined sabal and urtica extract compared with finasteride in men with benign prostatic hyperplasia: analysis of prostate volume and therapeutic outcome. BJU Int 2000;86:439-42.
    6764Boyle P, Robertson C, Lowe F, Roehrborn C. Meta-analysis of clinical trials of permixon in the treatment of symptomatic benign prostatic hyperplasia. Urology 2000;55:533-9.
    6765Di Silverio F, Monti S, Sciarra A, et al. Effects of long-term treatment with Serenoa repens (Permixon) on the concentrations and regional distribution of androgens and epidermal growth factor in benign prostatic hyperplasia. Prostate 1998;37:77-83.
    6769Levin RM, Das AK. A scientific basis for the therapeutic effects of Pygeum africanum and Serenoa repens. Urol Res 2000;28:201-9.
    6770Bayne CW, Ross M, Donnelly F, Habib FK. The selectivity and specificity of the actions of the lipido-sterolic extract of serenoa repens (permixon®) on the prostate. J Urol 2000;164:876-81.
    6771Strauch G, Perles P, Vergult G, et al. Comparison of finasteride (Proscar) and Serenoa repens (Permixon) in the inhibition of 5-alpha reductase in healthy male volunteers. Eur Urol 1994;26:247-52.
    6772Stepanov VN, Siniakova LA, Sarrazin B, Raynaud JP. Efficacy and tolerability of the lipidosterolic extract of Serenoa repens (Permixon) in benign prostatic hyperplasia: a double-blind comparison of two dosage regimens. Adv Ther 1999;16:231-41.
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