HERBAL THERAPY FOR BPH
Benign prostatic hyperplasia (BPH) is a common problem of aging for men. It has been proposed that the disorder has two phases, one that involves no clinical signs and the other that is manifested as disorders of urination from urinary tract obstruction by an enlarged prostate (1). In the first phase, there are microscopic changes within the prostate that may occur as early as the fourth decade of life and these may then be followed by macroscopic changes, namely enlargement of the prostate that typically begins during the fifth or sixth decade of life. However, clinical signs of the disorder occur only if the enlargement is substantial and becomes complicated by other disorders, such as prostatitis, or if the gland becomes hardened or deformed. The progression to clinical disease is most often seen after age 60. It is further suggested that while nearly all men will experience the microscopic changes in the prostate if they live long enough, only about half will experience prostate enlargement, and, of those, only about half will develop clinical symptoms. The question then arises: what causes the relatively common occurrence of prostate changes that lead to clinical disease?
Epidemiological studies have demonstrated that many of the same risk factors associated with cardiovascular diseases apply as risk factors for BPH. These risk factors include obesity, hypertension, and diabetes. The diabetes connection is considered especially strong; the risk is non-insulin dependent diabetes mellitus (NIDDM), which often involves excessive insulin levels, a possible direct contributor to the growth of the prostate (2, 3). As with cardiovascular disease, both exercise and moderate alcohol consumption appear to be protective for BPH. The influence of cigarette smoking on BPH has been unclear: some studies indicate a protective effect (there is a protective effect of smoking for ulcerative colitis that is well-established, so this result is not to be rejected out of hand), but other studies indicate a negative impact, at least for heavy smokers (4, 5)
Hormones affect the development and progression of BPH. Men with liver cirrhosis have a lower incidence of BPH than those who have normal liver function, probably because the liver damage reduces the metabolism of hormones to compounds that adversely influence BPH. Not all hormonal influences on BPH have been determined, but both sex hormones (estrogen, testosterone, prolactin) and insulin have been shown to have an effect thus far. In particular, it is thought that the conversion of testosterone to 5-alpha-dihydrotestosterone (DHT) may be a significant risk factor for BPH (6). The drug Finasteride suppresses DHT production by inhibiting the enzyme (5-alpha reductase) that converts testosterone to DHT, and this drug has been shown effective in reducing symptoms of BPH. DHT, produced in sebaceous glands, is also a contributor to male-pattern balding.
It is not known whether herbal, nutritional, or drug treatments for cardiovascular disease would also have an impact on BPH. However, the alpha-adrenoceptor agonist drug (Doxazosin) used for treating hypertension also appears to have therapeutic value for BPH (7).
Chinese medical literature has been relatively silent on the problem of BPH (8). Disorders of urination have been noted since ancient times, classified as "lin" syndromes. However, most times when obstruction of urination is noted, there are also accompanying signs mentioned that are not characteristic of BPH, such as blood in the urine or passing of stones or cloudy urine. Therefore, while BPH may have been experienced and treated as one of the lin syndromes, it is unclear whether any of the therapies were specific for BPH.
In Japan, BPH has been described by medical doctors who prescribe herbal therapies. These Kampo practitioners rely on a relatively small set of formulas from which one or two are selected for administration according to differential diagnosis by constitutional factors. Dr. Toyohiko Kikutani described his knowledge of such treatment methods, and this information was relayed by Hong-yen Hsu of the Oriental Healing Arts Institute. According to Kikutani, the most commonly used formula for BPH is Rehmannia Eight Formula (Bawei Dihuang Wan, also called Jingui Shenqi Wan). This formula is commonly used for disorders of aging, and is also applied in Japan for treating hypertension. The main alternatives to Rehmannia Eight Formula are prescriptions for blood stasis, such as Moutan and Persica Combination (Tonglong Tang) and Rhubarb and Moutan Combination (Dahuang Mudan Tang). The applications of these latter two formulas fit better with acute prostatitis rather than BPH, but this acute condition may trigger the clinical manifestation of the preclinical BPH. Sometimes the two approaches are combined: Dr. Domei Yakazu told of three patients receiving both Rehmannia Eight Formula and Moutan and Persica Combination. In an update by Dr. Hsu (9), he further mentioned combining Rehmannia Eight Formula with another blood-vitalizing prescription, Cinnamon and Hoelen Formula (Guizhi Fuling Wan), and use of Achyranthes and Plantago Formula (Niu Che Shenqi Wan), which consists of achyranthes and plantago added to the base of Rehmannia Eight Formula. Achyranthes and Plantago Formula is also used in Kampo medicine to treat diabetes, including nephritic and neurological effects of the disease.
Modern journals of Chinese medicine remain relatively silent on the subject. For example, no articles on BPH treatment have appeared in the English language Journal of Traditional Chinese Medicine or Chinese Journal of Integrated Traditional and Western Medicine. By contrast, the Western literature has numerous reports on therapies for BPH based on herbs.
Chinese researchers have addressed the problem of prostate disorders, but usually include a broad range of problems-dominated by acute prostatitis-in the study group, for which differential diagnosis is applied. Typical therapeutic categories are qi and blood stasis, damp-heat accumulation, and kidney-deficiency syndrome (10). The formulas administered vary considerably, but most formulations for treating qi and blood stasis include vacarria (wangbuliuxing); virtually all formulations for treating damp heat and urinary obstruction include plantago seed (cheqianzi). Kidney-deficiency formulations (subdivided into yin- and yang-deficiency categories) for prostate disorders usually incorporate herbs for treating blood stasis and damp heat as secondary components (19).
It is possible that the microscopic changes in the prostate in the early development of the disease process are consistent with microcirculation changes that are normally treated with blood-vitalizing herbs. Prostate enlargement is consistent with a damp-heat syndrome, since this syndrome is commonly associated with non-painful swelling in the lower abdomen. The final development of clinical symptoms of urination disorders may be associated with more severe blood stasis and damp heat coupled with weakening kidney qi. Thus, the three main diagnostic categories for prostate disorders may have relevance to BPH in terms of its development over several decades with a progression of the syndromes. Based on such a scenario, the therapy for clinical BPH with Chinese herbs would involve a combination of treating kidney deficiency as a solution for the constitutional disorder associated with aging, along with blood-vitalizing and damp-heat removing herbs as a treatment for the swollen prostate.
In accordance with traditional Chinese medicine doctrine, each patient should be treated on the basis of their actual syndrome. For example, yin-deficiency fire (treated by modification of Zhi Bai Dihuang Wan) or spleen- and lung-qi deficiency (treated by modification of Buzhong Yiqi Tang) could each be factors contributing to urinary disorders such as those seen with BPH. Nonetheless, most cases of BPH in essentially healthy men are likely to correspond to the disorder categories generalized above.
The treatment of BPH became a medical issue during the same time that cardiovascular disease therapy came to the fore, mainly during the 1970s. The incidence of these diseases had become very high, and the limited therapies available at the time provided inadequate results. In Germany, where herbal therapy (translated as phytotherapy) was still pursued by the pharmaceutical industry, the use of herbs was investigated at the same time as other researchers pursued surgical and drug options.
Dr. Hildebert Wagner, one of the leading proponents of phytotherapy (working at the Institute for Pharmaceutical Biology at the University of Munich), proposed investigation of the active components in Sabal serrulata for BPH in 1981 (11). This herb, now referred to as Serenoa serrulata or Serenoa repens, had been popular in the U.S. during the 19th century as a treatment for a variety of urino-genital disorders and had been mentioned as a treatment for prostate problems as early as 1899 (12). The fruit of the plant, a small palm referred to as saw palmetto (palmetto is Spanish for small palm; it has sharp, saw-like leaves) that is abundant in Florida, was used as a food for farm and ranch animals and as a medicine for humans.
Research into the effects of Serenoa in Germany, and subsequently in many other European countries, appeared to confirm a positive action on BPH, so that this became the principal use of the herb. By 1995, saw palmetto had become one of the 10 most extensively used Western herbs, with almost all of the commercial supplies going into products for BPH. The fruit is rich in sterols, which appear to be the primary active constituents. Although various proposals have been made as to how the sterols might affect BPH, the mechanism of action is still not clearly established. It is thought that the sterols may have, as one mechanism of action, the inhibition of DHT production (15).
At the same time, other Western herbs were investigated, with most attention falling to pumpkin seeds (Cucurbita pepo), nettle root (Urtica dioica or Urtica urens), bee pollen (particularly that from the rye plant), African potato (tubers of Hypoxis rooperi), and the large high-altitude African tree Pygeum africanum, also known as Prunus africanum (13, 14). In most cases, but particularly with pumpkin seeds and African potato, the main active components are understood to be the sterols, such as beta-sitosterol, which has been used as a therapeutic agent for BPH by itself (18). Triterpenoids in pygeum have also been proposed to be active components, reducing the swelling of the prostate (17).
Among the Chinese herbs recommended for BPH, the iridoid glycosides may be the active components: these include aucubin from plantago seed, catalpol from rehmannia, and morroniside from cornus (an ingredient in the rehmannia formulas). Iridoids have not been found in the Western herbal therapies for BPH and represent a potential new area for future investigation. Iridoids are the recognized active constituents of the Western herb chaste tree berry, Vitex agnus costus, which has been shown to reduce prolactin levels in women (20); elevated prolactin may be a risk factor for prostate enlargement in men. Triterpenoids found in vaccaria and alisma (an ingredient in rehmannia formulas) could contribute to their therapeutic effects, in a manner similar to those suggested for pygeum.
Today, products for BPH remain one of the primary commercial successes in the field of herbal medicine. The herbs are sold either individually or in combination products with 2 or 3 of the ingredients. The two most commonly-used substances, both as single herbs or in combination products, are saw palmetto and pygeum. The usual amount of saw palmetto provided in clinical studies is 320-480 mg of extract per day, in two divided doses (16). The usual amount of pygeum extract used in clinical trials is 100-200 mg/day (17). Treatment time is from 45 to 90 days to obtain significant improvement in symptoms; treatment time of 6 months has been reported to have a lasting effect for at least 18 months (18). Adverse effects of the herb therapies for BPH have not been reported.