• Published: 05 March 2009

Mayumi Suzuki, Yoshihiko Ito, Tomomi Fujino, Masayuki Abe, Keizo Umegaki, Satomi Onoue, Hiroshi Noguchi & Shizuo Yamada

Abstract

Saw palmetto extract (SPE), an extract from the ripe berries of the American dwarf palm, has been widely used as a therapeutic remedy for urinary dysfunction due to benign prostatic hyperplasia (BPH) in Europe. Numerous mechanisms of action have been proposed for SPE, including the inhibition of 5α-reductase. Today, α₁-adrenoceptor antagonists and muscarinic cholinoceptor antagonists are commonly used in the treatment of men with voiding symptoms secondary to BPH. The improvement of voiding symptoms in patients taking SPE may arise from its binding to pharmacologically relevant receptors in the lower urinary tract, such as α₁-adrenoceptors, muscarinic cholinoceptors, 1,4-dihyropyridine receptors and vanilloid receptors. Furthermore, oral administration of SPE has been shown to attenuate the up-regulation of α₁-adrenoceptors in the rat prostate induced by testosterone. Thus, SPE at clinically relevant doses may exert a direct effect on the pharmacological receptors in the lower urinary tract, thereby improving urinary dysfunction in patients with BPH and an overactive bladder. SPE does not have interactions with co-administered drugs or serious adverse events in blood biochemical parameters, suggestive of its relative safety, even with long-term intake. Clinical trials (placebo-controlled and active-controlled trials) of SPE conducted in men with BPH were also reviewed. This review should contribute to the understanding of the pharmacological effects of SPE in the treatment of patients with BPH and associated lower urinary tract symptoms (LUTS).

Introduction

Benign prostatic hyperplasia (BPH) and associated lower urinary tract symptoms (LUTS) are very common disorders in aging men. The prevalence of histopathologic BPH is age dependent, with initial development usually occurring after 40 years of age¹. By 60 years of age, its prevalence is greater than 50% and by age 85, the prevalence is as high as 90%. Similar to histological evidence, the prevalence of bothersome symptoms also increases with age. The two main forms of internationally accepted medical treatment for BPH are inhibitors of 5α-reductase, such as finasteride and α₁-adrenoceptor antagonists, with the latter being more effective². In addition to these medications, the ripe berries of the American dwarf palm (Serenoa repens, saw palmetto) have been traditionally used to treat genitourinary problems; to enhance sperm production, breast size, or libido; and as a mild diuretic³. In many European countries, phytotherapeutic agents, including saw palmetto, are very popular. Phytotherapeutic agents represent nearly half of the medications dispensed for the treatment of BPH in Italy, compared with 5% for α-blockers and 5% for 5α-reductase inhibitors⁴. In Germany and Austria, phytotherapy is the first-line treatment for mild to moderate lower urinary tract symptoms and represents more than 90% of all drugs prescribed for the treatment of BPH^4, 5, 6. Saw palmetto is a dwarf palm tree of the family Arecaceae and is indigenous to the southeastern parts of the United States. Saw palmetto berries have traditionally been used by American Indians to cure genitourinary disturbances, relieve mucous membrane irritations, increase testicular function, or increase breast size^5, 6. In the United States, the use of phytotherapy for LUTS has grown rapidly, and approximately 2.5 million men used saw palmetto extract (SPE), although a guideline panel did not recommend phytotherapy as a treatment for BPH^7, 8. In Japan, SPE is not a prescribed medication; however, it has been receiving increasing attention recently among patients with BPH.

The mechanisms of pharmacological action of SPE were not fully understood, although numerous proposals have been made, including inhibition of 5α-reductase, anti-androgenic effects, anti-proliferative effects, anti-inflammatory effects and anti-edema effects⁶. However, most of these pharmacological effects were observed at relatively high concentrations or large doses of SPE^9, 10, and it is uncertain whether the reported modes of action of SPE are therapeutically relevant^11, 12. As described above, α₁-adrenoceptor antagonists are commonly used in the treatment of men with voiding symptoms (urinary obstruction, pollakiuria and urinary incontinence) secondary to BPH. Goepel et al¹³ have shown that SPE might have α₁-adrenoceptor inhibitory properties. SPE significantly affects pharmacological receptors, such as the α₁-adrenoceptor and the muscarinic receptor in the lower urinary tract, to relieve the irritative and obstructive symptoms of dysuria due to BPH and LUTS¹⁴. In addition to traditionally used medications, like α₁-adrenoceptor antagonists, antimuscarinics, 5α-reductase inhibitors, and phytotherapy, several new therapeutic agents, such as selective β₃-adrenoceptor agonists, are potentially useful for treating LUTS suggestive of BPH, particularly for storage symptoms secondary to outflow obstruction¹⁵. Thus, the effects of SPE on these receptors in the lower urinary tract might be pharmacologically relevant.

To date, more than 11 placebo-controlled trials and 4 active-controlled trials with SPE in men with BPH have been conducted. Most of these were reported in the 1980s. Patient numbers were usually limited and the evaluation periods were relatively short, so it would be difficult to evaluate the effect of SPE and ascertain the efficacy of SPE in BPH patients. However, some placebo-controlled studies and comparisons to α₁-blockers have recently been conducted with relatively long-term treatments and sufficient numbers of patients^8, 16, 17.

Herbal products, including SPE, are often used with other prescription medications, and most patients with BPH are aged men. Elderly individuals frequently take dietary supplements with prescription drugs, and such a tendency will continue to increase in the near future. In such cases, a major concern is adverse events caused by a large excess intake or interactions between dietary supplements and drugs. Thus, the safety, as well as the efficacy, of these natural products and of their active ingredients remains to be analyzed at a scientific level. This review introduces newly revealed pharmacological actions of SPE, as well as some well-known mechanisms of action of SPE, and also summarizes clinical trials of SPE in comparison with currently used medicines.

Reference:

https://www.nature.com/articles/aps20091