Pygeum africanum for the Treatment of Mild-to-Moderate Benign Prostatic Hyperplasia

February 1999; Volume 2: 13-16

By Russell H. Greenfield, MD, FACEP

If you’re male and over age 60, chances are that you have experienced symptoms of benign prostatic hyperplasia (BPH). More than half of all men over age 60 have histologic evidence of BPH, an incidence that increases to almost 90% by age 80.1 The search for safe, effective medical intervention compels us to exam-ine the data behind the European practice of prescribing the herbal remedy Pygeum africanum for BPH treatment.

Pathogenesis of BPH

Prostatic growth spurts occur during puberty and the fifth decade of life, the latter episode being characterized by hypertrophy of smooth muscle, glandular epithelium, and stromal tissue in the periurethral region of the prostate.

This non-malignant growth is believed to occur as a result of hormonal processes, especially the conversion of testosterone to dihydrotestosterone (DHT) via the enzyme 5 alpha-reductase (5A-R). DHT has been shown to stimulate cellular proliferation within the prostate.2 In addition, rising levels of estrogen develop as men age. Estrogen appears to facilitate the activity of DHT by enhancing the amount of androgen receptor protein present in the tissue.3 Neither prostatic volume nor histopathology appear to correlate with severity of symptoms.4

Current Therapy

Symptoms include but are not limited to frequency, urinary urgency, weak urinary stream, and a sensation of incomplete emptying. Therapy for BPH should be individualized, since not all patients experience symptom progression.5 Patients with mild symptoms may not require any intervention, but should be evaluated periodically for a change in presentation. Surgery should be reserved for patients who develop complications of BPH such as urinary retention, renal insufficiency, gross hematuria, bladder stones, or recurrent urinary tract infections. For those patients whose symptoms are mild-to-moderate in sever-ity, a number of therapeutic agents have been developed that can relieve discomfort, improve quality of life, and potentially prevent the advent of adverse sequelae.

Botanical remedies have been widely used for BPH treatment in Europe and Africa, and have recently gained greater acceptance in the United States. Serenoa repens (saw palmetto) has been shown to improve urologic symptoms and flow measures with few side effects,6 as has beta-sitosterol.7 (See Alternative Medicine Alert, January 1998, pp. 1-4.) Similar benefits have been obtained with extracts of the African prune tree (Pygeum africanum).

Background and Biochemistry

Pygeum africanum is an evergreen native to the mountains of Africa. A traditional preparation made from its bark has been used for relief of bladder pains and difficulties with micturition.8 Unfortunately, unsustainable debarking is threatening the survival of the African prune tree. A standardized extract has been available in Europe for the treatment of mild-to-moderate BPH for almost 30 years under the name Tadenan. Constituents of the bark include lipid-soluble phyto-sterols and pentacyclic triterpenes that appear to act synergistically to improve the symptoms of BPH. The phytosterols, most notably beta-sitosterol, compete with androgen precursors9 and decrease intraprostatic prostaglandin levels, thereby reducing local inflammation.10 The triterpenes also act to minimize inflammation and may reduce edema formation via inhibition of glucosyl-transferase activity.11 Ferulic acid esters of fatty alcohols present in pygeum reduce the level of cholesterol in the prostate, limiting androgen synthesis.9 Pygeum africanum does not appear to have significant activity against 5A-R.12

Animal studies suggest that growth factor-stimulated fibroblast proliferation plays an important role in the development of BPH. Yablonsky et al showed that extracts of Pygeum africanum have antiproliferative effects on rat fibroblasts. The authors suggest that this activity may be at least partly responsible for the therapeutic effect of Pygeum africanum.13

Clinical Trials

An exhaustive review of the clinical research pertaining to Pygeum africanum was written by Andro and Riffaud in 1995.14 The review details the published clinical experience involving more than 2,000 patients from 25 years of open-label, non-comparative studies as well as double-blind, placebo-controlled studies. The majority of studies reveal a significant improvement in symptoms and, when measured, objective parameters. (See Table 1.)

Table 1
Double-blind, placebo-controlled studies of Pygeum africanum extract for BPH
Reference Daily Drug Dosage/Duration
n
Residual Volume
Nocturia
Maximum Flow
Other
Bongi Tadenan 75 mg 60 days
50
*
*
good response 88% poor response 12%
Barlet Tadenan 100 mg 60 days
255
*
*
+17%
66% report overall improvement
Dufour Tadenan 100 mg 6 weeks
120
78% report improvement
Bassi Pigenil 100 mg 60 days
40
75% report improvement
increased
dysuria improved in 11/18
Blitz Tadenan 100 mg 6 weeks
57
10% report improvement
77% report overall improvement
Maver Tadenan 100 mg 60 days
60
reduced in 23%
47% report improvement
Donkervoort Tadenan 100 mg 12 weeks
16
35% report improvement
no benefit
no evidence of benefit
Rizzo Tadenan 200 mg 60 days
40
*
*
+55%
*
Ranno Tadenan 200 mg 2 months
39
*
+91%
*
Frasseto Tadenan 200 mg 60 days
20
*
*

*Results not interpretable from source.
Adapted from: Andro M-C, Riffaud J-P. 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.
________________________________________________________________________________________________________

Of the 10 double-blind, placebo-controlled studies described in which pygeum was not combined with other agents, only one study found no significant urodynamic effect when compared with placebo.15 In general, the results obtained using a standardized extract of Pygeum africanum compare favorably to those reported with the use of pharmaceutical agents, especially 5A-R inhibitors.

One of the best studies16 evaluated the effect of 100 mg daily of Pygeum africanum on quantitative and qualitative parameters in 263 men with BPH being treated at eight different European centers. At the end of the two-month trial, statistically significant benefits of Pygeum africanum over placebo were noted with respect to maximum urinary flow rate, residual volume, nocturia, daytime frequency, and subjective assessment of improvement of symptoms.

Breza and coworkers performed an open, uncontrolled, multicenter trial of Tadenan use in 85 men with BPH.17 After a two-week washout period, patients were given 50 mg of the extract twice a day for two months. Measurements were continued for one month following the treatment protocol. At the end of the active intervention phase, statistically significant improvements were noted in quality-of-life scores and objective measurements of nocturia, urine volume, and mean maximal urinary flow rate. Clinical and symptomatic improvement was maintained during the post-treatment observation period, displaying a trend toward further improvement. Prostate size was unaffected by treatment with Tadenan.

A literature search for head-to-head in vivo comparison studies of Pygeum africanum vs. alpha-1 adrenergic blockers or 5A-R inhibitors for BPH revealed the lack of such data.

Adverse Effects/Drug Interactions

There have been no reports of sexual dysfunction associated with the use of Pygeum africanum, nor are there any known drug interactions. Side effects, most commonly gastrointestinal upset, occur infrequently. Extract constituents, some of which reportedly possess anticarcinogenic and antimutagenic properties, individually have safe toxicological profiles as well.14

The Commission E monographs do not include a review of pygeum.

Dosage/Formulation

Extracts of Pygeum africanum should be standardized to contain 14% triterpenes and 0.5% n-docosan-ol.18 Although Tadenan is not sold in the United States, pygeum is available and is also included in a number of herbal mixtures. Most authors recommend 100-200 mg daily in divided doses. We typically recommend that our patients with BPH begin with 50 mg twice a day. Some health food stores carry a Serenoa repens/Pygeum africanum combination tablet. The tablet form is preferred over taking pygeum as a tea. Pygeum is more expensive than saw palmetto but less than alpha-1 blockers. (See Table 2 for price comparison.)

Table 2
Price comparison of pygeum and saw palmetto
Manufacturer Formulation 
Price/Count
Pygeum
Upsher-Smith 50 mg standard
$24.99/60 capsules
Laboratories (Provol) bark extract
Nature’s Herbs 50 mg certified extract standardized for 6.5 mg sterols
$20.49/60 capsules
Solaray 50 mg extract
$17.98/60 capsules
Nutritional Dynamics 100 mg bark standardized 12-13% phytosterols
$16.95/30 capsules
Saw Palmetto
Natrol 160 mg berry extract
$14.95/60 capsules
Doctor’s Best 160 mg extract
$14.95/30 capsules
Schiff  100 mg berry extract/ 400 mg berry powder
$12.85/60 capsules
Nature’s Herbs 545 mg berries
$8.79/50 capsules
Combination Saw Palmetto/Pygeum
Solaray 100 mg pygeum extract/ 320 mg saw palmetto oil
$31.48/120 capsules
Nature’s Herbs 80 mg saw palmetto berry extract standardized/ 25 mg pygeum extract standardized 13% total sterols
$29.99/60 capsules

Source: Online mail-order firms
_________________________________________________________________________________

Conclusion

Standardized extracts of Pygeum africanum have been used for years in Europe and Africa for the treatment of BPH. They have been extensively studied for more than a quarter of a century and have been shown to be safe and effective. While the mechanism of action of this agent remains unclear, it is apparent that Pygeum africanum can be of benefit to some patients suffering from mild-to-moderate BPH.

Recommendation

Patients with mild-to-moderate BPH may be treated initially with either an alpha-1 adrenergic blocking agent or a standardized extract of saw palmetto. If the patient is elderly, on other antihypertensive agents, or has vascular headaches, I am more likely to use saw palmetto instead of alpha blockers. I do not use pygeum over saw palmetto because unsustainable debarking is threatening the survival of the African prune tree. However, in selected patients who have not experienced adequate symptomatic relief with saw palmetto, we have noted clinical improvement when pygeum was added to the therapeutic regimen.

Dr. Greenfield is a Fellow in the Program in Integrative Medicine at the University of Arizona in Tucson.

References

1. Berry SJ, et al. The development of human benign prostatic hyperplasia with age. J Urol 1984;132:474-479.

2. Tenover JS. Prostates, pates, and pimples. The potential medical uses of steroid 5 alpha-reductase inhibitors. Endocrinol Metab Clin North Am 1991;20:893-909.

3. Sagalowski AI, Wilson JD. Hyperplasia and carcinoma of the prostate. In: Fauci A, et al, eds. Harrison’s Principles of Internal Medicine, 14th ed. New York, NY: McGraw-Hill; 1998.

4. Lepor H. Nonoperative management of benign prostatic hyperplasia. J Urol 1989;141:1283-1289.

5. Jacobsen SJ, et al. Natural history of prostatism: Longitudinal changes in voiding symptoms in community dwelling men. J Urol 1996;155:595-600.

6. Wilt TJ, et al. Saw palmetto extracts for treatment of benign prostatic hyperplasia: A systematic review. JAMA 1998;280:1604-1609.

7. Berges RR, et al. Randomised, placebo-controlled, double-blind clinical trial of beta-sitosterol in patients with benign prostatic hyperplasia. Lancet 1995; 345:1529-1532.

8. Bombardelli E, Morazzoni P. Prunus africana (Hook. f.) Kalkm. Fitoterapia 1997;68:205-218.

9. Schulz V, et al. Rational Phytotherapy. 3rd ed. New York: Springer-Verlag; 1998:232-233.

10. Zahradnik HP, et al. Prostaglandin content in prostatic adenomas after treatment with a sterol. Fortschr Med 1980;98:69-72.

11. Kozai K, et al. Inhibition of glucosyltransferase from Streptococcus mutans by oleanolic acid and ursolic acid. Caries Res 1987;21:104-108.

12. Rhodes L, et al. Comparison of finasteride (Proscar), a 5 alpha-reductase inhibitor, and various commercial plant extracts in in vitro and in vivo 5 alpha-reductase inhibition. Prostate 1993;22:43-51.

13. Yablonsky F, et al. Antiproliferative effect of Pygeum africanum extract on rat prostatic fibroblasts. J Urol 1997;157:2381-2387.

14. Andro M-C, Riffaud J-P. 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.

15. Donkervoort T, et al. A clinical and urodynamic study of tadenan in the treatment of benign prostatic hypertrophy. Eur Urol 1977;3:218-225.

16. Barlet 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. Wien Klin Wochenschr 1990;102:667-673.

17. Breza J, 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;14:127-139.

18. Prostate enlargement. In: Murray M, Pizzorno J. Encyclopedia of Natural Medicine. 2nd ed. Rocklin, CA: Prima Publishing; 1998.