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Benign Prostatic Hyperplasia (BPH)

 

This is a condition resulting from the enlargement of the prostate which causes compression, elongation, displacement and distortion of the prostatic urethra leading to the obstruction of urine flow. The incidence of BPH increases with age.

Epidemiological studies have revealed that when a man reaches approximately 40 years of age, the prostate gland has already started to enlarge; approximately 50% of men aged 60 years and 90% of those aged 85 years have BPH.

Symptoms of BPH vary in severity and include: 

  • frequent urination 
  • nocturia (excess urination at night)
  • urinary urgency or hesitancy
  • painful and difficult urination (dysuria)
  • Mechanism of Enlargement of the Prostate Gland
    Normal growth and functioning of the prostate is influenced by male sex hormones (androgens), especially testosterone from the testes and the adrenal glands. Free testosterone is taken up by the prostate cells where it is converted to dihydrotestosterone (DHT) by the enzyme 5 alpha-reductase.

    FREE Testosterone --------------(enzyme 5 alpha reductase)-------- DHT

    DHT is physiologically more active than testosterone and is mainly responsible for prostatic growth and enlargement in BPH. DHT concentrations are four to five times higher than testosterone in an enlarged prostate gland. The binding of DHT to androgen receptors in prostate cells is necessary for intracellular activity of testosterone. DHT appears to be very active in the prostate because it has a much higher affinity for androgen receptors than does testosterone. DHT is metabolized into biologically inactive metabolites by steroid oxidoreductase enzymes. A minor fraction of testosterone is also metabolized to 17 ?-estradiol by aromatase. 17 ? -estradiol also contributes to the growth of prostatic tissue. Recently, these growth factors have been reported to contribute to the enlargement of the prostate gland. These growth factors may stimulate the growth of the prostate gland by direct action or by a prostaglandin pathway. Prostatic fluid from patients suffering from BPH and chronic prostatitis has been shown to have higher amounts of PGE2 (a pro-inflammatory prostaglandin) than prostatic fluid from men with a normal prostate.

    Conventional Treatment: Medical research for the development of anti-BPH therapy has focused on 5 alpha-reductase inhibition.

    Finasteride: This is a synthetic 4-azasteroid compound, a specific inhibitor of steroid Type II 5alpha-reductase, an intracellular enzyme that converts the androgen testosterone into 5 alpha-dihydrotestosterone (DHT). Finasteride is effective in less than 50% of patients but has to be administered for 6 months to a year to determine if the patient will respond to the therapy. In controlled clinical trials of 12-month duration, the following clinical adverse reactions were reported as possibly, probably or definitely drug-related in patients treated with PROSCAR or placebo, respectively: erectile dysfunction (3.7%, 1.1%), decreased libido (3.3%, 1.6%) and decreased volume of ejaculate (2.8%, 0.9%). Adverse effects reported in post-marketing experience for PROSCAR (finasteride 5 mg) are breast tenderness and enlargement, as well as hypersensitivity reactions, including lip swelling and skin rash.

    Complementary Approach
    Plants have been used for centuries in the treatment of urinary problems. Many plants have been subjected to laboratory and clinical evaluations. The results of these evaluations have confirmed the safety of such plants for prolonged use. In Germany and Austria, plant-based products are the first line of treatment for BPH and make up more than 90% of total prescriptions for BPH. Based on scientific evaluations, the Commission E Special Expert Committee of the Federal Health Agency of Germany, the German equivalent to the U.S. FDA, has recently approved pumpkin seed and saw palmetto berries for the treatment of BPH. These plants may act by inhibiting the enzyme 5 alpha-reductase, responsible for the conversion of testosterone to DHT.

    Pumpkin Seeds
    The four dominant fatty acids are palmitic, stearic, oleic and linoleic acids. These four fatty acids make up 98 +/- 0.13% of the seeds` oil. (1) The exact active ingredients responsible for the actions of pumpkin seed are not known, however sterols and fatty acids appear to be responsible for its anti-prostatic effect. The oil fraction of pumpkin seed has been shown to inhibit 5 alpha-reductase. The mixture of delta 7-sterols has been shown to inhibit the binding of DHT to androgen receptors. The tocopherol present in pumpkin seed oil may also regulate the tone of bladder smooth muscle. In a randomized, double-blind study, the preparation Curbicin, obtained from pumpkin seeds and dwarf palm plants (Cucurbita pepo L. and Sabal serrulata), was compared with a placebo in the treatment of symptoms caused by prostatic hyperplasia. 53 patients took part in the study, which was carried out over a 3-month period. Urinary flow, micturition time, residual urine, frequency of micturition and a subjective assessment of the effect of treatment were all significantly improved in the treatment group. No untoward side effects were noted. (2)

    Saw Palmetto Extract
    This contains fatty acids (lauric, myristic, oleic, linoleic and linolenic), phytosterols (beta-sitosterol and its glucosides, stigmasterol and campesterol) and high molecular weight fatty alcohols (docosanol, hexacosanol, octacosanol and triacontanol). The fatty acids, notably lauric and myristic acids, present in saw palmetto extract are mainly responsible for 5 alpha-reductase inhibition. 18 beta-sitosterol, which is present in the highest quantities, may act by competing with endogenous estrogens for receptor sites, thereby reducing the overall estrogenic effect.

    The effectiveness of Sabal serrulata (dwarf palm) extract was evaluated in the treatment of 38 patients with symptomatic prostatic hyperplasia. During a 12-month treatment controlled by investigations the subjective symptoms decreased in nearly three fourths of the patients. Side effects were not observed. According to uro flow metric investigations the average peak flow value increased from 10.36 ml/sec to 14.44 ml/sec (p < 0.0001) and the average mean flow value from 0.02 ml/sec to 7.45 ml/sec (p < 0.001). After treatment residual urine volume decreased or was nil in more than 9/10 of the cases. The average decrease of residue was 47 ml (p < 0.001).

    The average decrease in prostatic volume was 10.6%. On the basis of their favorable experience the authors recommend the administration of sabal serrulata extract in the treatment of patients with mild or moderate symptoms of prostatic hyperplasia. Other studies suggest additional spasmolytic activity of sabal serrulata and improvement of the quality of life of the patients. (4) (5) (6).

    Pygeum Africanum Extract
    This is available in many countries, including those in central and eastern Europe, for the treatment of mild to moderate BPH. Its efficacy and acceptability have been demonstrated in numerous open and placebo-controlled studies in large populations. In a placebo-controlled, double-blind multicenter study done in Europe the overall assessment at the end of therapy, showed that micturition improved in 66% of the patients treated with pygeum africanum extract, as compared with an improvement of 31% in the placebo group. The difference was significant at the statistical level of p less than 0.001. During therapy with pygeum africanum extract, gastrointestinal side effects occurred in 5 patients. (263 patients study group). (3)

    Magnesium
    Mg plays an important role as an activator of enzymes (phosphatases) involved in ATP metabolism, thus affecting both katabolic and anabolic processes. (14) (15)

    Vitamin E
    This vitamin is an important micronutrient in chemoprevention and prostate health. (10)

    Zinc
    The prostate gland concentrates Zn more than any organ in the body. The prostate concentration of zinc is ten times lower in cancer of the prostate than in normal prostate or BHP. There is an altered intermediary metabolism of prostate cells in the pathogenesis of prostate adenocarcinoma (PCa) and the progression of malignancy. Evidence which implicates the metabolic transformation of citrate-producing sane ? cells to citrate-oxidizing malignant cells in the process of malignancy.

    The accumulation of high intracellular levels of zinc by prostate cells induces mitochondrial apoptogenesis. This represents a newly identified physiological effect of zinc in the regulation of prostate cell growth. Zinc, which is accumulated in prostate cells at much higher levels than in other cells, inhibits m-aconitase activity thereby minimizing citrate oxidation. Zinc inhibits human prostatic carcinoma cell growth, possibly due to induction of cell cycle arrest and apoptosis. There now exists strong evidence that the loss of a unique capability to retain high levels of zinc is an important factor in the development and progression of malignant prostate cells. (7) (8) (10) (11) (12) (13)

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