All About Natural Testosterone - Chapter 9b

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Maximize Your Vitality & Potency For Men Over 40

By Jonathan V. Wright, M.D. and Lane Lenard, Ph.D.
$14.95 - 256 pages, softcover
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Chapter 9b

Effects of Saw Palmetto Extract in Men With BPH

The vast majority of trials of saw palmetto extract in men with BPH have demonstrated it to be an effective and exceptionally safe therapeutic option. The most important of these studies are those that included large numbers of men and/or employed a double-blind, placebo-controlled, or comparative design.

In a large, multicenter, open-label trial* conducted in Belgium by 112 urologists, supervised by the University of Brussels urologist Dr. Johan Braeckman, 505 men with mild to moderate symptoms of BPH took saw palmetto extract (160 mg, twice daily) for three months. The results demonstrated impressive improvement in these men. As shown in Figure 9-1, the maximum urinary flow rate increased by 17% after 45 days of treatment, and by 25% after 90 days, compared with the pretreatment baseline. Similar increases were observed in mean urinary flow rates. Residual urinary volume (the amount of urine remaining in the bladder after a urination attempt) was 20% lower than baseline at both time points, and prostatic volume (the size of the prostate) was reduced by 9 and 10% after 45 and 90 days, respectively. The International Prostate Symptom Score (IPSS), based on a brief patient questionnaire, is a standardized measure of prostate symptoms. IPSS scores were decreased by 22 and 35%, respectively. All these differences were statistically significant. The only relevant measure that showed no significant change was PSA level.14

(* In an open-label study, both the investigators and the participants know what the experimental substance is. There is no placebo control.)

Braeckman's results may be discounted by some for the lack of a placebo control. This was not the case with a study by a French team headed by Dr. G. Champault, of l'Hôpital Jean Verdier in Paris. Using a double-blind, placebo-controlled design, these researchers asked 110 men with symptoms of BPH to take either saw palmetto extract (Permixon®) (160 mg, twice daily) or placebo for 30 days. Under these more rigorous experimental conditions, saw palmetto extract produced clearly superior results, compared with both pretreatment baseline and placebo. As shown in Figure 9-2, those taking saw palmetto extract experienced large, statistically significant improvements in the frequency of nighttime trips to the toilet, urinary flow rate, and residual urine volume.

Saw Palmetto Extract vs Proscar®

How does saw palmetto extract compare with Proscar®? Only one published study has compared the two treatments in men with BPH. This was a very large, double-blind, French-based trial supervised by Dr. Jean-Christophe Carraro, of the Pierre Fabre Médicament, and conducted in 87 different urology centers in nine European countries.9 The 1,098 men, all over age 50, were randomly asked to take either Permixon® (160 mg, twice daily) or Proscar® (5 mg, once daily) for six months. Neither the men nor the physicians who administered the treatments knew who was getting which treatment.

The results showed that both treatments were equally effective in reducing the symptoms of BPH. As shown in Figure 9-3, both treatments were associated with essentially equivalent improvements in prostate symptoms (about 22% at 6 weeks, 40% at 26 weeks), quality of life (about 54% at 6 weeks; 70% at 26 weeks), and urine flow rate (about 15% at 6 weeks, 25-30% at 26 weeks). The only significant difference between the two treatments on these measures was a slight advantage for Proscar® in peak urinary flow rate at 26 weeks.

In terms of sexuality, however, the Permixon-treated men fared significantly better. The Proscar-treated men complained substantially more about decreased libido, impotence, and ejaculatory disorders. As the authors wrote, "Patients receiving finasteride experienced statistically significant deterioration in sexual function score compared to those receiving Permixon®. The difference between the two groups, which was in favor of Permixon® for all four items of the questionnaire, was noted from the first follow-up visit at six weeks and remained significant at 26 weeks."9

Although both treatments were equally effective in decreasing symptoms of BPH, Proscar® was associated with a significantly greater (-16%) reduction in prostate size compared with Permixon® (-7%). How is this possible, if according to the conventional medical wisdom, BPH symptoms are a result of an enlarged prostate?

This finding underscores a fact, demonstrated by other research, that prostate symptoms and urinary flow rates are not necessarily directly related to prostate size. The authors suggest two possible explanations for this apparent discrepancy: 1) The decrease in prostate volume associated with 5-α-reductase inhibition may not necessarily occur in the part of the prostate where BPH develops and obstructs urinary flow. 2) Intensified 5-α-reductase activity may not necessarily be the sole or even the most important cause of BPH.

Proscar® also caused a large drop in PSA levels, where Permixon® had no effect. The reason for this difference is also unclear (as is its clinical significance), but it may be related to the exclusion from the study of men with elevated PSA levels and/or a greater reduction in PSA-producing prostate epithelial cells by the 5-α-reductase inhibitor.

Taken together, these results reinforce the contention that the laser-beam approach to BPH therapy represented by high-tech synthetic drugs, whose only effect is to inhibit 5-α-reductase, may be misdirected. On the contrary, the broader therapeutic approach represented by saw palmetto extract, with its multiple avenues of attack, is not only equally effective in reducing symptoms, but more tolerable.

The results of the Carraro et al study essentially represent the European view of BPH treatment. What do scientists on this side of the Atlantic Ocean think about saw palmetto versus finasteride? Curiously, it is hard to find a positive word about saw palmetto in the U.S. literature. Unlike Carraro, the results of the only two other published comparative studies suggest that finasteride is the superior treatment.

You don't have to look too far to find the source of this apparent discrepancy. While the Carraro et al study was conducted by a large group of independent researchers (the paper was not supported by funds from any pharmaceutical company), the two pro-finasteride papers were published by scientists employed by - you guessed it - Merck & Co., the manufacturer of Proscar®. A close examination of these papers indicates that their primary purpose was to try to convince physicians - based on some very flimsy and contrived science - that, despite what they may have heard about saw palmetto, Proscar® was superior for treating men with BPH, because only Proscar really gets to the root of the problem - 5-α-reductase inhibition. This is not to say that these researchers have lied, made up data, or otherwise misrepresented the facts. On the other hand, these papers are excellent illustrations of the way apparently good science can be manipulated to stack the experimental deck in favor of a particular point of view. Let's look at these two papers and see what was done.

The Rhodes study. The first study, by Rhodes et al,4 was published in 1993 (three years before Carraro et al). It was an in-vitro (test tube) and in-vivo (lab rats and human subjects) comparison of the relative ability of finasteride and saw palmetto (and other plant extracts) to inhibit 5-α-reductase.

In the introduction, the authors lay the groundwork for their ultimate conclusion by pointing out that, the "decrease in intra-prostatic DHT is thought to cause the decrease in prostate volume seen in men treated with finasteride." Their support for this statement comes from a 1992 paper by Stoner,15 who coincidently, also worked for Merck. Given this "fact," it takes no great leap to conclude that anything that reduces DHT should also reduce prostate volume. The authors acknowledge that saw palmetto extract has been shown in European studies to have the ability to inhibit

5-α-reductase.3-6 They fail to note at this point,* however, that the same study (by Sultan et al) they cite to support saw palmetto extract's anti-5-α-reductase activity also showed that it inhibits the enzyme 3-ketosteroid reductase and binding to androgen receptors.3

(* They do mention it later in the Discussion section, buy only to discount the reality of this effect.)

In the in-vitro studies, finasteride was found to be 5,600 times more potent at inhibiting 5-α-reductase than saw palmetto extract, but neither substance was found to have any ability at all to inhibit binding at androgen receptors. While the first result comes as no surprise (after all, that's what finasteride was designed to do), the second result is contradicted by several other studies.3-6

In Rhodes's animal study, pre-pubertal rats were castrated and then given doses of either "testosterone" (testosterone propionate) or "DHT" (DHT propionate). Half the animals in each androgen group also received either saw palmetto extract (Permixon®) or finasteride for seven days. Both the natural extract and the drug were given at doses that can only be described as "really high" and "unbelievably high," at least in human terms. The dose of Permixon® given to these very young rats (weighing all of 50 grams) was either 180 mg or 1,800 mg per day. The low dose is just half the total dose normally given to a full-sized human being, while the high dose is more than five times the human dose. The doses of finasteride - 0.1 and 10.0 mg/day - were 2% and 200%, respectively, of the human dose. Whatever the results, given the magnitude of these doses, it's hard to imagine they could have any significance for human males aged 50 or older.

The results of the animal study showed that both "testosterone" and "DHT" stimulated rat prostate growth. As expected due to its mechanism of action, finasteride blocked prostate growth by 33% in the "testosterone"-treated rats, but not at all in the "DHT"-treated ones. Saw palmetto extract had no effect - "even at the highest dosage levels" - on prostate growth. Under these experimental conditions, finasteride, indeed, comes out smelling better. Seven days is a very short time when it comes to prostate growth, however. Recognizing this, most saw palmetto studies in the scientific literature have lasted for many months, even up to a year.

In the human phase of Rhodes's study, Proscar®, Permixon®, or placebo was given to 32 healthy young male "volunteers." This time standard human doses were used, but again, the duration of the study was just seven days. Predictably, the results demonstrated the superiority of finasteride for significantly reducing the level of DHT in the blood stream. In terms of clinical superiority, the relevance of these results for middle-aged or older men with BPH of a seven-day study in healthy young men is not really all that clear, especially if you question the importance of DHT for excess prostate growth.

Nevertheless, the underlying message of Rhodes et al couldn't be clearer:

If, DHT causes prostatic hyperplasia; and
if finasteride is thousands of times more potent an inhibitor of 5-α-reductase than saw palmetto extract; and
if finasteride reduces DHT formation, while saw palmetto extract does not; and
if finasteride blocks "testosterone"-stimulated prostate growth, but saw palmetto extract does not; and
if neither treatment inhibits androgen receptor binding (despite what you may have read elsewhere about saw palmetto); then
finasteride must be the superior treatment for men with BPH.

Of course, Rhodes et al (and presumably Merck's legal department) are careful not go so far as to actually make any claims of clinical efficacy for finasteride based on these data,* but they pull no punches when it comes to saw palmetto extract. Let's analyze what they say in their Conclusions and see what it really means:

(* This article was published in 1993, before Merck had received official FDA approval to market -- and therefore, make any therapeutic claims for -- Proscar®.)

What they say...

"Based on our data, it is unlikely that Permixon...or other plant extracts assayed would cause prostate shrinkage via inhibition of 5-α-reductase or binding to the androgen receptor."

What it really means ...

It's true that Permixon probably does not cause prostate shrinkage by inhibiting 5-α-reductase. That doesn't mean it might not work some other way, including via androgen receptor binding. It also assumes that prostate shrinkage is important for symptomatic relief. The authors' dubious conclusion that saw palmetto extract does not bind androgen receptors contradicts the European literature. They get away with this conclusion by using the "weasel" phrase, "Based on our data..." Good scientists do not draw conclusions based solely upon their own data. But what they have done here is to discount saw palmetto's other therapeutic effects by suggesting the possibility that the earlier European studies were somehow mistaken.

What they say...

"There are published results of multiple short-term clinical studies using various plant extracts, including Permixon . . . However, none have measured prostate volume effects or serum DHT in men."

What it really means ...

This statement is true. However, it fails to mention two important facts. First, saw palmetto extract is widely considered effective by physicians who use it. (It is officially "approved" for reducing BPH symptoms in Germany and several other countries.) Second, according to several studies, prostate volume and serum DHT levels may not be all that important in the etiology of BPH.

What they say...

"In contrast, finasteride is a potent, specific 5-α-reductase inhibitor. It inhibits testosterone stimulated growth in the rat, inhibits human prostatic 5-α-reductase in vitro at very low doses, and has been shown to shrink the human prostate and reduce serum DHT in long-term clinical trials."

What it really means ...

Having taken saw palmetto extract off the table as a therapeutic option, the authors now roll out their "superior," new alternative. In advertising-speak, this would be their "take-home" message. It reinforces the conventional wisdom that 5-α-reductase inhibition is the key to the shrinking of hyperplastic prostate tissue, and the best way currently available to do that is finasteride.

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