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Effect of coconut oil on testosterone-induced prostatic hyperplasia in Sprague Dawley rats
Abstract
Benign prostatic hyperplasia (BPH) is the benign uncontrolled growth of the prostate gland, leading to difficulty with urination. Saw palmetto lipid extracts (SPLE), used to treat BPH, have been shown to inhibit prostate 5a-reductase, and some major components, such as lauric, myristic and oleic acids also inhibit this enzyme. Coconut oil (CO) is also rich in fatty acids, mainly lauric and myristic acids. We investigated whether CO prevents testosterone-induced prostate hyperplasia (PH) in Sprague-Dawley rats. Animals were distributed into seven groups (10 rats each). A negative control group were injected with soya oil; six groups were injected with testosterone (3 mg kg(-1)) to induce PH: a positive control group, and five groups treated orally with SPLE (400 mg kg(-1)), CO or sunflower oil (SO) (400 and 800 mg kg(-1)). Treatments were given for 14 days. Rats were weighed before treatment and weekly thereafter. Rats were then killed and the prostates were removed and weighed. CO (400 and 800 mg kg(-1)), SPLE (400 mg kg(-1)) and SO at 800 mg kg(-1), but not at 400 mg kg(-1), significantly reduced the increase in prostate weight (PW) and PW:body weight (BW) ratio induced by testosterone (% inhibition 61.5%, 82.0%, 43.8% and 28.2%, respectively). Since CO and SPLE, but not SO, contain appreciable concentrations of lauric and myristic acids, these results could be attributed to this fact. In conclusion, this study shows that CO reduced the increase of both PW and PW:BW ratio, markers of testosterone-induced PH in rats.
... Saw palmetto's putative mechanism of action is inhibition of 5α-reductase, the enzyme that converts testosterone into the more potent androgen dihydrotestoterone [5][6][7][8][9][10]. Studies that have found saw palmetto administration or treatment reduced androgen action support this belief [11][12][13][14][15]; however, not all studies have found that saw palmetto inhibits 5α-reductase or has anti-androgen action [16][17][18]. The believed bioactive components of saw palmetto are fatty acids and phytosterols. ...
... Saw palmetto extract decreased testosterone-induced prostate hyperplasia [15] in rats and prostate cancer progression in TRAMP mice [14]. A number of studies have found that saw palmetto supplements improve lower urinary tract symptoms (LUTS) in men suffering from BPH. ...
... Others have also measured fatty acid [15,20,[41][42][43] or phytosterol content [42,44,45] of saw palmetto, but despite the reported differences in saw palmetto supplement contents, to the best of our knowledge, no one has characterized both the fatty acid and phytosterol contents of commercially available supplements or compared different supplement categories. Thus, we set out to characterize these saw palmetto supplement components, hypothesizing that we would find large differences in their quantities and composition. ...
... Benign prostatic hyperplasia (BPH) is an enlargement of the prostate gland from progressive hyperplasia or abnormal growth of cells of glandular epithelial and stromal cells. It is associated with impairment in urinary function, as such it is a common urogenital disorder that affects up to 85% of men over 50 years of age (Arruzazabala et al., 2007). The inability to delay urination, incomplete emptying of the bladder, bladder outlet obstruction, bloody urination, nocturia, as well as dysuria, are common symptoms of BPH (Barkin, 2011). ...
... Drugs, such as Finasteride® developed with a focus to reducing DHT level in BPH patients have been associated with side effects such as nasal congestion, decreased libido, erectile dysfunction and so on. Thus, to reduce these side effects as well as suppress BPH development, the management of the condition has come to include dietary interventions as well as natural materials such nutraceutical preparations which include pumpkin seed oil (Gossell-Williams et al., 2006), coconut oil (Arruzazabala et al., 2007) as well as herbal extracts mainly saw palmetto lipid extracts (SPLC) (Arruzazabala et al., 2007). Over the last few decades, there has been a growing public concern about the significant interplay between health, food and nutrition. ...
... Drugs, such as Finasteride® developed with a focus to reducing DHT level in BPH patients have been associated with side effects such as nasal congestion, decreased libido, erectile dysfunction and so on. Thus, to reduce these side effects as well as suppress BPH development, the management of the condition has come to include dietary interventions as well as natural materials such nutraceutical preparations which include pumpkin seed oil (Gossell-Williams et al., 2006), coconut oil (Arruzazabala et al., 2007) as well as herbal extracts mainly saw palmetto lipid extracts (SPLC) (Arruzazabala et al., 2007). Over the last few decades, there has been a growing public concern about the significant interplay between health, food and nutrition. ...
Anti-androgenic substances, mainly prostate 5α-reductase inhibitors, used in the treatment of benign prostatic hyperplasia (BPH) have been associated with side effects in man and animals. To reduce these side effects as well as suppress BPH development, the management of the condition has come to include dietary interventions. This study investigated the effect of some cooking oils on testosterone-induced hyperplasia of the prostate in rats. Male Sprague-dawley rats were distributed into eighteen groups (n=6) as A-R. A negative control group was injected subcutaneously with soya oil; while prostatic hyperplasia was induced subcutaneously in groups B-R with 3mg/kg testosterone daily for 14days. Group B was the positive control (BPH group) while groups C-R were also administered orally 800mg/kg of coconut, castor, canola, cottonseed, pomegranate, blackseed, sheabutter, olive oil, codliver, sardine, palm, repeatedly heated palm (RHPO), vegetable, repeatedly-heated vegetable (RHVO), sesame, and groundnut oils respectively, daily, for 14 days. Blood sample was drawn via retro-orbital sinus for the estimation of serum testosterone(T) and dihydrotestosterone (DHT) level and rats were thereafter euthanized to obtain the prostates for T and DHT determination as well as tissue weights. Data are mean ± SEM, compared by ANOVA. The oils significantly reduced the increase in prostate weight (PW) to body weight (BW) ratio induced by testosterone. Apart from the fact that all the oils reduced the PW:BW ratio, the blackseed, sheabutter, sardine, vegetable and groundnut oils suppressed the DHT level in the serum, while pomegranate, olive, RHPO reduced DHT level in the prostate compared to the BPH rats. This study suggests that blackseed, sheabutter, sardine, vegetable, groundnut, pomegranate, olive, and RHPO oils could inhibit testosterone-induced hyperplasia of the prostate and therefore may be beneficial in the management of BPH.
... Coconut oil extracted from coconut (Cocos nucifera) is composed mostly of a mixture of triglycerides containing a high proportion of medium-chain saturated fatty acids, especially myristic acid and lauric acid (de Lourdes Arruzazabala et al., 2007;Kamariah et al., 2008). Because virgin CO is obtained from fresh, matured coconut kernel without the use of heat and without undergoing refining process, it is believed to be rich in antioxidant vitamins and phenolic compounds (Nevin & Rajamohan, 2004). ...
... Furthermore, it is known that increases in lipid peroxidation are a function of the degree of unsaturation of the fatty acids present in the phospholipids of biological membranes (Gavazza & Catal a, 2006). The adverse effects of CO due to its longchain fatty acids composition and medium-chain fatty acids contents have been reported previously (de Lourdes Arruzazabala et al., 2007). We therefore speculate that the intake of CO strongly modifies testicular membrane lipid composition, increasing their vulnerability to peroxidative changes. ...
... ml (2 ml kg À1 equivalent to 1840 mg kg À1 body weight) to rats that weighed between 128 and 148 g. Surprisingly, CO at this dose increased testicular lipid peroxidation and altered the sperm quality profiles of the animals. Although the doses used in the above studies are relatively high compared with the quantities of CO commonly used in food and nutritional products (de Lourdes Arruzazabala et al., 2007) and also compared with the dose used in our own study, it seems likely that higher dosages of CO in diets would have better health benefits than lower dosages. This pattern of biphasic dose-response effect on the testis has been observed in the reproductive toxicology studies of several endocrine-disrupting chemicals (Calabrese & Baldwin, 2001) including, for example cadmium (Gunnarsson et al., 2003) and atrazine (Abarikwu et al., 2011). ...
This study was conducted to compare the effects of administration of coconut oil (CO) and Moringa oleifera oil (MO) on testicular oxidative stress, sperm quality and steroidogenesis parameters in rats treated with mercury chloride (HgCl2 ). After 15 days of oral administration of CO (2 ml kg(-1) body weight) and MO (2 ml kg(-1) body weight) along with intraperitoneal (i.p.) administration of HgCl2 (5 mg kg(-1) body weight) alone or in combination, we found that CO treatment did not protect against HgCl2 -induced poor sperm quality (motility, count) as well as decreased testosterone level and 17β-hydroxysteroid dehydrogenase (17β-HSD) activity. Treatment with CO alone decreased glutathione (GSH), and glutathione peroxidase (GSH-Px) activities and increased malondialdehyde (MDA) level in rat's testis, whereas MO did not change these parameters. Cotreatment with MO prevented HgCl2 -induced testicular catalase (CAT) and superoxide dismutase (SOD) activities, poor sperm quality and low testosterone level and also blocks the adverse effect of CO+HgCl2 (2 ml kg(-1) body weight + 5 mg kg(-1) body weight) on the investigated endpoints. In conclusion, MO and not CO decreased the deleterious effects of HgCl2 on sperm quality and steroidogenesis in rats and also strengthen the antioxidant defence of the testes. Therefore, MO is beneficial as an antioxidant in HgCl2 -induced oxidative damage.
... BPH is reported in approximately 50% of patients aged 50 years or older [5], and, according to another report, the estimated prevalence of BPH is 26.2% of the world population [6]. BPH is closely related to various lower urinary tract symptoms (LUTSs), such as urinary incontinence, urgency, and frequency; acute urinary retention; urinary hemorrhage; urethral infection; bladder stones; and renal failure [7,8]. Testosterone (TE) secretion decreases with aging. ...
Gut microbes are closely associated with disease onset and improvement. However, the effects of gut microbes on the occurrence, prevention, and treatment of benign prostatic hyperplasia (BPH) are still unclear. We investigated the alteration of gut microbiota with implications for the diagnosis, prevention, and treatment of BPH and identified correlations among various indicators, including hormone indicators, apoptosis markers in BPH, and finasteride treatment models. BPH induction altered the abundance of Lactobacillus, Flavonifractor, Acetatifactor, Oscillibacter, Pseudoflavonifractor, Intestinimonas, and Butyricimonas genera, which are related to BPH indicators. Among these, the altered abundance of Lactobacillus and Acetatifactor was associated with the promotion and inhibition of prostate apoptosis, respectively. Finasteride treatment altered the abundance of Barnesiella, Acetatifactor, Butyricimonas, Desulfovibrio, Anaerobacterium, and Robinsoniella genera, which are related to BPH indicators. Among these, altered abundances of Desulfovibrio and Acetatifactor were associated with the promotion and inhibition of prostate apoptosis, respectively. In addition, the abundances of Lactobacillus and Acetatifactor were normalized after finasteride treatment. In conclusion, the association between apoptosis and altered abundances of Lactobacillus and Acetatifactor, among other gut microbes, suggests their potential utility in the diagnosis, prevention, and treatment of BPH.
... 29 The phytosterols, which can be found in sesame seed oil, coconut oil and the like, have the ability to lower the amount of 5-α-reductase in the liver by up to 44% and in the prostate by up to 33%. 30,31 From the above the discussion it was clear that the ingredients of Amarantha hair oil have been proved to be effective on hair loss and premature greying. Also majority of ingredients possess 5-α-reductase/hair growth promoting, anti-androgenic, hair conditioning, natural dyeing and colouring activities. ...
p class="abstract"> Background: Androgenetic alopecia is a common form of hair loss in both men and women. Synthetic drugs like minoxidil and finastride are available treatment for androgenetic alopecia, however, use of these drugs on long term basis may cause many side effects. Hence there was a need to have an effective and safe alternative option. Ari Healthcare Pvt. Ltd. has developed Amarantha hair oil (herbal hair oil) to be used for dandruff, hair fall and premature greying of hair. The aim was to standardize Amarantha hair oil with special reference to identification of β-sitosterol as major component having 5α-reductase inhibitory activity/hair growth promoting activity.
Methods: Amarantha hair oil was prepared by using various herbal ingredients which contains β-sitosterol as active marker compound. Amarantha hair oil was evaluated for appearance, weight per ml, refractive index, acid value, saponification value, peroxide value, TLC Identification of β-sitosterol, assay of β-sitosterol content using high performance thin layer chromatography (HPTLC) and microbiological tests. Also accelerated stability study was performed.
Results: All the parameters tested were within normal limits. Amarantha hair oil was stable in accelerated stability study. We found that almost all the ingredients of formulation contain β-sitosterol when analysed using HPTLC. Amarantha hair oil contains 0.52% of β-sitosterol.
Conclusions: All the ingredients and Amarantha hair oil contain β-sitosterol that helps in promotion of hair growth.
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... With increase in age, testosterone secretion decreases gradually, and testosterone is converted to dihydrotestosterone (DHT) in the presence of 5-alpha reductase; DHT acts as an endogenous ligand with high biological activity, being 2-3-fold and 15-30-fold more sensitive to androgen receptors than that of testosterone and adrenal androgens, respectively [12]. The production and accumulation of DHT in the prostate increases with age and cell proliferation that promotes the development of prostate tissue to induce BPH [13][14][15] and is mainly related to lower urinary tract symptoms such as frequent urination, dysuria, hematuria, urinary retention, and urinary tract infection [11,16,17]. ...
Testosterone undecanoate is a hormone agent with long-acting potential and is used for testosterone replacement therapy for hypogonadism. This study was designed to investigate application of testosterone undecanoate in maintaining high androgen levels for inducing benign prostatic hyperplasia more conveniently than that for testosterone propionate. We conducted two-part studies to determine the optimal dosage and dosing cycle for efficient and stable induction of benign prostatic hyperplasia using testosterone undecanoate. In the injection dosage substudy, single testosterone undecanoate dose (125, 250, 500, 750, or 1000 mg/kg body weight) was administered, and the optimal concentration was determined for 8weeks by measuring changes in testosterone, dihydrotestosterone, and 5-alpha reductase levels. And then, testosterone undecanoate was administered at the optimal dose at intervals of 1, 2, 3, or 4 weeks for 12weeks to induce benign prostatic hyperplasia. The injection dosage substudy showed dose-dependently higher and more stable levels of testosterone in groups administrated testosterone undecanoate than in groups administered testosterone propionate. In the injection cycle substudy, testosterone undecanoate-administered group stably maintained high levels of testosterone, dihydrotestosterone, and 5-alpha reductase compared with testosterone propionate-administered group for the same injection cycle; moreover, the prostate measurements, an important sign of benign prostatic hyperplasia, were significantly increased. Based on these two substudies, we determined the optimal conditions for inducing benign prostatic hyperplasia stably and more conveniently than that for testosterone propionate. This study suggests an extended application of testosterone undecanoate for inducing benign prostatic hyperplasia that can improve research reliability considering the half-life of testosterone as well as injection dosage and concentration.
... VCO was believed to be more beneficial than copra oil because of its extraction, which retained so much more biologically active components like vitamin E and polyphenols (Wallace, 2019). There were notwithstanding expanded testosterone levels, coconut crude oil (CNO) decreased the danger of prostatic cancer by fundamentally decreasing increment in prostate to the bodyweight proportion instigated by testosterone, which has incited the examination (De Lourdes et al., 2007). VCO was known to be listed as a valuable source by many authors as a potent medicine. ...
This study investigated the preventive effect of virgin coconut oil (VCO) on the epithelium thickness and the diameter of the seminiferous tubules induced by ethanol in mice (Mus musculus). This study used 20 male mice as the experimental animal which were divided into five groups with four mice in each group. Negative control (C-) was given 2% Tween and aquadest, while positive control (C+) was given 2% Tween and 33% ethanol. T1, T2, and T3 were respectively given 0.09, 0.19, and 0.37 mL/kg bw VCO and 33% ethanol (0.2 mL/kg bw). VCO was given orally for 39 days, and ethanol was given orally seven days later for 32 days. Ethanol was administered two hours after the VCO administration. Analysis of variance followed by Tukey’s range test on the epithelium thickness and the diameter of the seminiferous tubules showed significant differences (p <0.05) of C+ group from the other groups. Whereas, there was no significant difference (p >0.05) was found among C-, T1, T2 and T3 group. The result concluded that VCO could protect the testis of mice from the damage caused by ethanol.
... The 5α-reductase inhibitory activity of coconut oil in a testosterone induced prostate hyperplasia in rat inhibited the growth of prostate enlargement (Arruzazabala et al., 2007). Pumpkin seeds (Cucurbita pepo) reduces protein binding prostate levels, prostate weight and improve histology of prostate tissue. ...
Insulin acts alone for the survival of Diabetic Mellitus of type I.
However, Type II may require insulin for correction of hyperglycemia for
therapeutic approach. But now the diabetic patients are treated by thiamine
supplementation. This chapter describes the process involved in maintenance
of glucose level in blood circulation, hormonal control of glucose
homeostasis, classification of diabetes mellitus, role of thiamine in normal
glucose metabolism and relationship of thiamine and diabetes mellitus.
... Simultaneously, group 1, as negative controls, were administered with normal saline alone, group 2 were considered BPH model, groups 3 and 4 were orally treated with 400 and 800 mg/kg of the oil of N. sativa seed, respectively, group 5 were administered with 0.5 mg/kg oral finasteride and considered positive control [16]. The doses of N. sativa seed oil were selected according to previous studies [17,18]. All groups received repeated testosterone injections for the following four weeks after BPH induction (Fig. 1). ...
Background:
Benign prostatic hyperplasia (BPH) is the most prevalent disease of the prostate in elderly men. Since Nigella sativa has been reported to show various pharmacological effects, this study was conducted to examine the effect of N. sativa seed oil on experimental BPH.
Methods:
The oil was extracted using the cold-pressing method. Fifty rats were divided into five groups of 10 each as follows: Group 1 orally (p.o.) received normal saline; groups 2-5 were castrated and subcutaneously received 5 mg/kg testosterone propionate for four weeks. Group 2, namely, BPH model, underwent no further treatment, Groups 3 and 4 were treated with 400 mg/kg and 800 mg/kg N. sativa seed oil, Group 5 received finasteride (0.5 mg/kg, p.o.) for 28 days. All groups received repeated testosterone injections for the following four weeks after BPH induction. After the treatments, rats were sacrificed and the prostate tissues removed. Wet weight, prostatic volume (PV) and prostatic index (PI) were determined. Serum prostate-specific antigen (PSA), dihydrotestosterone (DHT), malondialdehyde (MDA) and antioxidant levels were determined.
Results:
Our results showed that oral treatment with 400 and 800 mg/kg N. sativa oil led to a significant decrease in PI, PV, DHT concentration, PSA, and serum MDA level, and also significantly increased serum antioxidant capacity.
Conclusions:
The study demonstrated that the oil seed exerted anti-BPH effects which may be associated with its antioxidant properties in vivo.
... The 5α-reductase inhibitory activity of coconut oil in a testosterone induced prostate hyperplasia in rat inhibited the growth of prostate enlargement (Arruzazabala et al., 2007). Pumpkin seeds (Cucurbita pepo) reduces protein binding prostate levels, prostate weight and improve histology of prostate tissue. ...
... The 5α-reductase inhibitory activity of coconut oil in a testosterone induced prostate hyperplasia in rat inhibited the growth of prostate enlargement (Arruzazabala et al., 2007). Pumpkin seeds (Cucurbita pepo) reduces protein binding prostate levels, prostate weight and improve histology of prostate tissue. ...
Benign prostatic hyperplasia (BPH) is one of the most common
urological disease in aging men, associated with lower urinary tract
symptoms (LUTS). A better understanding of the prostate physiology,
function, and pathogenesis has led to the development of promising
therapeutic agents, useful in the management of clinical BPH in men. The
specific approach used to treat BPH depends upon a number of factors like
age, prostate size, weight and severity of the symptoms. Watchful waiting,
pharmacological therapy, and surgery are also helpful for the BPH patients,
depending on the severity of the disease. Although conventional drug
therapy (alpha1 -blockers, 5α-reductase inhibitors) and surgery
(prostatectomy, transurethral resection, etc.) seem to be most effective for
patients with clinical BPH, herbal medicines (Serenoa repens, Pygeum
africanum, Urtica dioica etc.) are also commonly used in patients with mild
to moderate symptoms. This article provides a brief account of the rationale
and efficacy of different treatment options currently available in the
management of BPH.
... The 5α-reductase inhibitory activity of coconut oil in a testosterone induced prostate hyperplasia in rat inhibited the growth of prostate enlargement (Arruzazabala et al., 2007). Pumpkin seeds (Cucurbita pepo) reduces protein binding prostate levels, prostate weight and improve histology of prostate tissue. ...
... The 5α-reductase inhibitory activity of coconut oil in a testosterone induced prostate hyperplasia in rat inhibited the growth of prostate enlargement (Arruzazabala et al., 2007). Pumpkin seeds (Cucurbita pepo) reduces protein binding prostate levels, prostate weight and improve histology of prostate tissue. ...
The process of programmed cell death (PCD), or apoptosis, are triggered
by external and internal stimuli such as ultraviolet radiation, oxidative stress,
ROS, DNA damage etc. It is an intrinsic cell-suicide programmed for
maintaining tissue homeostasis and safeguard the organism by demise of
infected cell. Recently, many potent apoptosis-inducing drugs associated
with human health have been recorded that prevent cancer and other related
diseases. Therefore, research mainly focus on the cell cycle analysis and
signaling pathways that control cell cycle arrest and programmed cell death.
Failure of apoptotic machinery can cause many diseases in human such as
cancer. The goal of this chapter are to provide a general overview of
molecular mechanisms of apoptosis, function of apoptosis in animal,
regulation of apoptosis, process of necrosis, different types of disease
associated with apoptosis as well as an alternative forms of apoptosis.
... Benign prostatic hyperplasia (BPH) is an uncontrolled proliferation of the both epithelial and stromal cells that occurs in the transitional zone of the prostate gland. Clinically, it is characterized by presenting lower urinary tract symptoms (LUTS), nocturia, sepsis, irreversible bladder failure, and even death (Arruzabala et al., 2007;Pais, 2010). BPH is one of the common prostate problems experienced by around 85% of men above the age group of 45 years (Sarma and Wei, 2012). ...
Benign prostatic hyperplasia (BPH) is a common urological disorder of elderly men, which is characterized by hyperplasia
of prostatic stromal and epithelial cells. The present study was designed to investigate the inhibitory effect of the
Aqueous Bark Extract of Dillenia indica L. (ABEDI) in the BPH rat model. The male rats were treated either corn oil or
testosterone (10 mg/kg) dissolved in corn oil and testosterone with ABEDI (100 and 500 mg/kg) consecutively for three
weeks. The inhibitory effect of ABEDI on BPH was illustrated by prostate weight, prostatic index, prostate epithelial
height, percentage of inhibition and histological examinations. ABEDIcaused significant reduction in the prostate weight
and prostatic index compared to testosterone induced BPH model group. Serum ALT and creatinine levels did not differ
among different experimental groups, when compared with a positive control group. ABEDItreated group also ameliorated
the hyperplasia of prostate epithelium in a similar manner as observed in the finasteride (5 mg/kg) treated group. This
study indicates that ABEDIsignificantly reduced the progression of BPH and it may be another phytotherapeutial source of
drugs in BPH treatment.
... Serenoa serrulata, también conocida como Serenoa repens o Sabal serrulata, es una especie vegetal cuyos componentes presentan un efecto inhibidor de la 5a-reductasa 2,10-12 . Este aspecto, ha sido estudiado en numerosos ensayos realizados en hiperplasia de próstata y adenocarcinoma de próstata [13][14][15][16] . Se cree que los principios activos responsables de este efecto son sus ácidos grasos, que constituyen un 90% de su extracto y son ricos en ácido laúrico (12:0) y ácido mirístico (14:0) 17 , ácidos grasos saturados. ...
... Lauric and myristic acids (Fig. 5) present in high concentrations in coconut oil attributed to its 5-alpha reductase inhibitory activity. Further experimental studies are required to explore coconut oil in men with BPH [109]. ...
Benign prostatic hyperplasia (BPH) the most common condition in aging men is the non malignant enlargement of the prostate gland with increase in numbers of both epithelial and stromal cells within the periurethal transition zone of the prostate. Sources of symptoms in patient with BPH appear to be both static and dynamic component. Management of BPH has undergone a rapid evolution over the past decade to aid men with lower urinary tract symptoms attributed to bladder outlet obstruction. Treatment of clinical BPH aims to improve symptoms, prevent urinary tract infections, avoid renal insult, relief obstruction and improve bladder emptying.Prostate cancer patients and those with benign prostatic hyperplasia are increasingly exploring the use of plant derived non-nutritive compounds with protective or disease preventive properties, especially due to long term side effects of pharmacological treatment and risk of mortality associated with surgical procedures. Phytotherapeutic preparations are plant extracts with different components obtained by different extraction procedures. Numerous mechanisms of action have been postulated for mono and combination plant extracts. This article give a brief account of rationale and efficacy of various existing phytotherapeutic agents in the management of benign prostatic hyperplasia, including the herbs which hold the potential promise are also mentioned , although much research is still required.
... Serenoa serrulata, también conocida como Serenoa repens o Sabal serrulata, es una especie vegetal cuyos componentes presentan un efecto inhibidor de la 5a-reductasa 2,10-12 . Este aspecto, ha sido estudiado en numerosos ensayos realizados en hiperplasia de próstata y adenocarcinoma de próstata [13][14][15][16] . Se cree que los principios activos responsables de este efecto son sus ácidos grasos, que constituyen un 90% de su extracto y son ricos en ácido laúrico (12:0) y ácido mirístico (14:0) 17 , ácidos grasos saturados. ...
Introduction: female androgenetic alopecia (FAGA) and telogen effluvium (TE) are common causes of hair loss in women. A known fact in these types of alopecia is the increased activity of 5a-reductase which reduces testosterone to dihydrotestosterone, accelerating hair cycle and shortening its duration. Serenoa serrulata is a plant species whose components have an inhibitory effect on 5a reductase. Objective: the main objective of this study was to evaluate the efficacy and tolerance against female alopecia of a food supplement with Serenoa serrulata extract, L-cystine, tocotrienol-tocopherol complex, iron, zinc, and vitamins H, B1, B2, B3, B5, B6 and B12 administered daily for six months. Material and Methods: single-center, open-label, nonrandomized, single-blind, 180-days pilot study conducted in women with FAGA or TE. The study assessed the macroscopic appearance of the hair, hair density by microphotograph, the anagen / telogen ratio (A/T) by trichogram, and the number of detached hair by combing and wash tests. Self-assessment survey of the results was performed. Results: the mean age of participants (n = 10) was 40 ± 15.5 years. FAGA and ET had an evolution of 4.5 ± two years and three months, respectively. After treatment the participants had an average increase of 6.9% in the proportion of hairs in anagen phase, and the mean A/T ratio increased to 3.3. Eighty percent or patients showed an increased capillary density at study end. After three months, all participants had a mean reduction of hair loss of 56% vs baseline. Ninety percent perceived a greater or equal amount of hair at the end of the study and 80% noticed it stronger. No adverse effects induced by treatment were observed. Conclusions: the good results of the analyzed variables suggest a therapeutic benefit against FAGA and ET. Additional research is warranted to confirm the observed data.
... Recently, in most part of tropical countries, coconut water is being consumed as beverage with health benefits that contains sugar, dietary fiber, proteins, antioxidants, vitamins and minerals and provides an isotonic electrolyte balance. Researches revealed that coconuts may help benign prostatic hyperplasia (De Lourdes et al. 2007) and virgin coconut oil reduces total cholesterol, triglycerides, phospholipids, LDL and VLDL cholesterol levels and increased HDL cholesterol in serum and tissues (Kuntiya et al. 2004). ...
Pleurotus, commonly known as oyster mushroom, is a wood rotting mushroom that naturally grows on decaying logs. This mushroom has been cultivated using saw dust based substrate formulation. This study was undertaken to evaluate the growth performance of Pleurotus citrinopileatus, Pleurotus djamor and Pleurotus salmoneostramineus on coconut water gelatin and different physical factors such as pH, aeration, illumination and temperature conditions. Coconut water gelatin supported the mycelial growth of the three species as indicated by the luxuriant mycelial growth. Pleurotus citrinopileatus recorded fastest and shortest mycelial growth (90mm) after six days of incubation while Pleurotus salmoneostramineus showed slower mycelial growth (63.55mm), thick mycelial density and longest incubation period of eight days. Moreover, the three species grew best in pH 8.0, incubated either sealed or unsealed, both dark and lighted conditions at room temperature.
... Coconuts may help benign prostatic hyperplasia (de Lourdes et al. 2007). In rats, virgin coconut oil reduced total cholesterol, triglycerides, phospholipids, LDL, and VLDL cholesterol levels and increased HDL cholesterol in serum and tissues (Nevin and Rajamohan 2004). ...
The paper summarizes results of a research aimed at assessing of the pulp properties of Cocos nucifera (coconut) for using coconut as an alternative raw material for pulp and paper industry. Total experiments were 11 in two stages and the pulping procedure was kraft pulping. In the first stage, the pulp was cooked at 170, 160 and 150oC for 90 minutes. The effective alkali and sulfidity for every constant temperature were 13.5 and 20%; 17.5 and 25% and 21.3 and 30%. In the second stage, the pulp was cooked at 170oC for 60 and 30 minutes for 21.3% effective alkali and 30% sulfidity. The screened pulp was beaten at 3000 revolution. The pulp properties were examined for both beaten and unbeaten pulp. . The cooked pulp at 160oC and 90 min with 21.3% effective alkali and 30% sulfidity produced good result based on properties. The yield, tear index and tensile index were respectively 44.4%, 9.11 mN.m2/g and 95.2 N.m/g. There is an opportunity to use it as an alternative raw material for pulp and paper industry.
... The extraction of VCNO from the fresh endosperm of coconut is believed to be more beneficial than usually prepared copra oil because its mode of extraction retains more biologically active components such as vitamin E and polyphenols (Nevin & Rajamohan, 2004). A recent study conducted by De Lourdes et al. (2007) showed that despite increased testosterone levels, CNO decreased the risk of prostatic cancer by significantly reducing increase in prostate: body weight ratio induced by testosterone. Though research has reported the use of CNO in a number of biological conditions, there is a dearth of literature on its use as a pro-fertility agent. ...
The present study explored the effect of virgin coconut oil on oxidative stress, testosterone and
gonadotropic hormones in alcohol-induced testicular injury. Twenty-five male rats were randomly
assigned to one of five groups (n=5). The oil was processed from the mature endosperm of
coconut and administered at 6.7 ml/kg body weight, while alcohol was given orally at 7 ml/kg
body weight. After sacrifice, testicular malondialdehyde and serum hormone levels were
determined. Testicular malondialdehyde levels increased significantly in animals treated with
alcohol alone (p < 0.001), and animals treated with alcohol following virgin coconut oil treatment
(p < 0.05) while the other groups showed a significant decrease (p < 0.05) when compared with
the control. However, when compared with the group treated with alcohol alone, all the other
groups showed a significant decrease (p < 0.05) in testicular malondialdehyde level. Serum
testosterone levels increased significantly (p < 0.05) in rats treated with virgin coconut oil when
compared with the alcohol-only treated group, while serum FSH and LH levels were not
significantly different from the control values in all the treatment groups. Virgin coconut oil
effectively lowered alcohol-induced oxidative stress by reducing testicular malondialdehyde levels
and ameliorated the deleterious effect of alcohol on serum testosterone level, but showed no
effect on serum FSH and LH levels.
... The biochemical analysis of the endosperm revealed the presence of terpenoids, alkaloids, resins, glycosides, steroids, and flavonoids [76, 77]. Medically, coconut is reported to have efficacy against prostatic hyperplasia [78], anti-helmintic activity [79], and antimicrobial and antiviral activities [80], vasorelaxant, antimalarial [81], and anti-hypertensive; activities, and inhibitory effect on oral microflora [82]. Furthermore, its bioactive compounds were found to have extended efficacy on agropest control [83]. ...
Lymphatic filariasis is a parasitic infection that causes a devastating public health and socioeconomic burden with an estimated infection of over 120 million individuals worldwide. The infection is caused by three closely related nematode parasites, namely, Wuchereria bancrofti, Brugia malayi, and B. timori, which are transmitted to human through mosquitoes of Anopheles, Culex, and Aedes genera. The species have many ecological variants and are diversified in terms of their genetic fingerprint. The rapid spread of the disease and the genetic diversification cause the lymphatic filarial parasites to respond differently to diagnostic and therapeutic interventions. This in turn prompts the current challenge encountered in its management. Furthermore, most of the chemical medications used are characterized by adverse side effects. These complications urgently warrant intense prospecting on bio-chemicals that have potent efficacy against either the filarial worms or thier vector. In lieu of this, we presented a review on recent literature that reported the efficacy of filaricidal biochemicals and those employed as vector control agents. In addition, methods used for biochemical extraction, screening procedures, and structure of the bioactive compounds were also presented.
... Coconuts may help benign prostatic hyperplasia (de Lourdes et al. 2007). In rats, virgin coconut oil reduced total cholesterol, triglycerides, phospholipids, LDL, and VLDL cholesterol levels and increased HDL cholesterol in serum and tissues (Nevin and Rajamohan 2004). ...
The paper summarizes results of a research aimed at assessing of the pulp properties of Cocos nucifera (coconut) for using coconut as an alternative raw material for pulp and paper industry. Total experiments were 9 and the pulping procedure was kraft pulping. The pulp was cooked at 170, 160 and 1500C for 90 minutes. The active alkali and sulphidity (%) for every constant temperature were 15 and 20%; 20 and 25% and 25 and 30%. The screened pulp was beaten at 3000 revolution. The pulp properties were examined for both beaten and unbeaten pulp. . The cooked pulp at 1600C and 90 min with 25% active alkali and 30% sulphidity produced good result after beating based on cooking temperature and properties. The yield, brightness (ISO), tear index and tensile index were respectively 44.42%, 16.44%, 9.11 mN.m2/g and 95.17 Nm/g. There is an opportunity to use it as an alternative raw material for pulp and paper industry.
Background and Objectives: Periodontal pocket treatment must be carried out with the aim of eliminating
or reducing the microbial population and biomechanically removing necrotic tissue in the gingival sulcus
which is a medium for microbial growth and preventing re-infection so that periodontal pockets or gingivitis
can occur. Indonesia is a tropical country that has a high diversity of plants that must be utilized properly, one
of which is widely used as a dental material. This study was to determine the examination of Sarang Semut
(Myrmecodia Pendens) extract as a basic antimicrobial ingredient for periodontal pocket therapy and gingivitis.
Methodology: The experimental animals that were given treatment were 20 male Wistar rats which were
divided into 5 groups; 1 positive control group was given 0,02 % chlorhexidine (CHX), 1 negative control group
was given equates and 3 experimental group were given Sarang Semut extract with dose 1 mg, 10 mg, 100
mg.
Results: Histopathological results of test animal organs given test preparations and autopsied 24 hours
after treatment showed abnormalities in the form of renal tubular epithelial degeneration, peribronchiolitis.
Perivasculitis and hydropic degeneration of the liver. The histopathological results of the test animals that were
autopsied on the 14th day after treatment showed foci of inflammation in the liver.
Conclusions: These results of examination of Sarang Semut extract can be used as a basic antimicrobial
ingredients for periodontal pocket therapy at a dose of less than 100 mg.
Keywords
Sarang Semut, Myrmecodia Pendens, Wistar Rats, Antimicrobial, Periodontal Pocket
Plant-derived 5 α-reductase inhibitors, such as β-sitosterol and phytosterol glycosides, have been used to treat androgenic alopecia, but their oral absolute bioavailability is poor. This study aimed to develop a transdermal drug delivery system of β-sitosterol (BS) using a nanostructured lipid carrier (NLC) incorporated into polymeric microneedles (MN). Using a high-speed homogenization method, NLC was formulated variables were optimized by Box-Behnken statistical design. The optimized formulation of BS-loaded NLCs was incorporated into the chitosan-based MNs to prepare NLC-loaded polymeric MNs (NLC-MNs) and evaluated using testosterone induced alopecia rats. The cumulative amount of β-sitosterol associated with NLC- MN which penetrated the rat skin in-vitro was 3612.27 ± 120.81 μg/cm2, while from the NLC preparation was 2402.35 ± 162.5 μg/cm2. The steady state flux (Jss) of NLC-MN was significantly higher than that of the optimized NLC formulation (P < 0.05). Anagen/telogen ratio was significantly affected by NLC and NLC-MN, which was 2.22 ± 0.34, 1.24 ± 0.18 respectively compared to 0.26 ± 0.08 for animal group treated with testosterone. The reversal of androgen-induced hair loss in animals treated with β-sitosterol was a sign of hair follicle dominance in the anagenic growth phase. However, NLC–MN delivery system has shown significant enhancement of hair growth in rats. From these experimental data, it can be concluded that NLC incorporated MN transdermal system have potential in effective treatment of androgenic alopecia.
Prostate cancer (CaP) is one of the leading causes of death in men worldwide. Much attention has been given on its prevention and treatment strategies, including targeting the regulation of 5-alpha-Reductase (5αR) enzyme activity, aimed to limit the progression of CaP by inhibiting the conversion of potent androgen dihydrotestosterone from testosterone that is thought to play a role in pathogenesis of CaP, by using the 5-alpha-Reductase inhibitors (5αRis) such as finasteride and dutasteride. However, 5αRis are reported to exhibit numerous adverse side effects, for instance erectile dysfunction, ejaculatory dysfunction and loss of libido. This has led to a surge of interest on plant-derived alternatives that might offer favourable side effects and less toxic profiles. Phytochemicals from plants are shown to exhibit numerous medicinal properties in various studies targeting many major illnesses including CaP. Therefore, in this review, we aim to discuss the use of phytochemicals namely phytosterols, polyphenols and fatty acids, found in various plants with proven anti-CaP properties, as an alternative herbal CaP medicines as well as to outline their inhibitory activities on 5αRs isozymes based on their structural similarities with current 5αRis as part of CaP treatment approaches.
Prostate cancer (CaP) is one of the leading causes of death in men worldwide. Much attention has been given on its prevention and treatment strategies, including targeting the regulation of 5-alpha-Reductase (5αR) enzyme activity, aimed to limit the progression of CaP by inhibiting the conversion of potent androgen dihydrotestosterone from testosterone that is thought to play a role in pathogenesis of CaP, by using the 5-alpha-Reductase inhibitors (5αRis) such as finasteride and dutasteride. However, 5αRis are reported to exhibit numerous adverse side effects, for instance erectile dysfunction, ejaculatory dysfunction and loss of libido. This has led to a surge of interests on plant-derived alternatives that might offer favourable side effects and less toxic profiles. Phytochemicals from plants are shown to exhibit numerous medicinal properties in various studies targeting many major illnesses including CaP. Therefore, in this review, we aim to discuss on the use of phytochemicals namely phytosterols, polyphenols and fatty acids, found in various plants with proven anti-CaP properties, as an alternative herbal CaP medicines as well as to outline their inhibitory activities on 5αRs isozymes based on their structural similarities with current 5αRis as part of CaP treatment approaches.
Prostate cancer (CaP) is one of the leading causes of death in men worldwide. Much attention has been given on its prevention and treatment strategies, including targeting the regulation of 5-alpha-Reductase (5αR) enzyme activity, aimed to limit the progression of CaP by inhibiting the conversion of potent androgen dihydrotestosterone from testosterone that is thought to play a role in pathogenesis of CaP, by using the 5-alpha-Reductase inhibitors (5αRis) such as finasteride and dutasteride. However, 5αRis are reported to exhibit numerous adverse side effects, for instance erectile dysfunction, ejaculatory dysfunction and loss of libido. This has led to a surge of interests on plant-derived alternatives that might offer favourable side effects and less toxic profiles. Phytochemicals from plants are shown to exhibit numerous medicinal properties in various studies targeting many major illnesses including CaP. Therefore, in this review, we aim to discuss on the use of phytochemicals namely phytosterols, polyphenols and fatty acids, found in various plants with proven anti-CaP properties, as an alternative herbal CaP medicines as well as to outline their inhibitory activities on 5αRs isozymes based on their structural similarities with current 5αRis as part of CaP treatment approaches.
This study was aimed at determining the effect of different dosages of coconut oil on the histology of the testis. The rats in the control group were administered with distilled water while those in the low, moderate and high dose groups were administered with coconut oil extract of 0.5, 1.1 and 2.2ml/kg body weight respectively once daily for fourteen days. On day 14 of the experiment, the rats were sacrificed. The testes of rats from various groups were carefully dissected out and weighed. There was no significant decrease (p<0.05) in mean testicular weight of the treated rats; low dose (1.14±0.05), moderate dose (1.16±0.05) and high dose (1.12±0.06) groups compared to the control rats (1.20±0.04). The histological sections revealed proliferation of seminiferous epithelium especially that of the high dose group. In conclusion, coconut oil has no deleterious effect on the histology of the testes and could lead to increased spermatogenesis.
Keywords: Cocos nucifera, testis, histology, spermatogenesis
to evaluate the histological and histochemical changes induced by human chorionic gonadotropin on the adult prostate and to correlate the changes with the level of testosterone
Recent studies have been trying to find out how diet and metabolic changes such as dyslipidaemia, hyperglycaemia and hyperinsulinaemia can stimulate cancer progression. This investigation aimed to evaluate the effect of high concentrations of fatty acids and/or glucose in tumour prostate cells, focusing on the proliferation/migration profile and oxidative stress. PC3 cells were treated with high concentration of saturated fatty acid (palmitate, 100µM), glucose (220 mg/dL) or both for 24 or 48 h. Results demonstrated that PC3 cells showed a significant increase in proliferation after 48 h of treatment with glucose and palmitate + glucose. Cell proliferation was associated with reduced levels of AMPK phosphorylation in glucose group at 24 and 48 h of treatment, while palmitate one presented this result only after 48 h of treatment. Also, there was a significant increase in cell migration between time 0 and 48 h after all treatments, except in the control. Catalase activity was increased by palmitate in the beginning of treatment, while glucose presented a later effect. Also, nitrite production was increased by glucose only after 48 h, and the total antioxidant activity was enhanced by palmitate in the initial hours. Thus, we conclude that the high concentration of the saturated fatty acid palmitate and glucose in vitro influences PC3 cells and stimulates cellular activities related to carcinogenesis such as cell proliferation, migration and oxidative stress in different ways. Palmitate presents a rapid and initial effect, while a glucose environment stimulates cells later on, maintaining high levels of cell proliferation.
Cocos nucifera (coconut) is a well-known plant used in the Indian and African system of medicine. Folklore medicine claims its uses in diabetes, diarrhea, cancer, etc. Research carried out using different in vitro and in vivo techniques of biological evaluation supports most of the claims. This review presents the medical properties of the fruit of the plant.
Quisqualis indica (QI) has been used for treating disorders such as stomach pain, constipation, and digestion problem. This study was aimed to evaluate the therapeutic efficacy of QI extract on treating benign prostatic hyperplasia (BPH) in LNCaP human prostate cancer cell line and a testosterone-induced BPH rat model. LNCaP cells were treated with QI plus testosterone propionate (TP), and androgen receptor (AR) and prostate specific antigen (PSA) expression levels were assessed by Western blotting. To induce BPH, the rats were subjected to a daily subcutaneous injection of TP (3 mg/kg) for 4 wk. The rats in treatment group were orally gavaged with QI (150mg/kg) together with the TP injection. In-vitro studies showed that TP-induced increases in AR and PSA expression in LNCaP cells were reduced by QI treatment. In BPH-model rats, the prostate weight, testosterone in serum, DHT concentration and 5α-reductase mRNA expression in prostate tissue were significantly reduced following the treatment with QI. TP-induced prostatic hyperplasia and the expression of proliferating cell nuclear antigen (PCNA) and cyclin D1 were significantly attenuated in QI-treated rats. In addition, QI induced apoptosis by up-regulating caspase-3 and -9 activity and decreasing the B-cell lymphoma 2 (Bcl-2)/Bcl-2-associated X protein (Bax) ratio in prostate tissues of BPH rats. Further investigation showed that TP-induced activation of AKT and glycogen synthase kinase 3β (GSK3β) was reduced by QI administration. Therefore, our findings suggest that QI attenuates the BPH state in rats through anti-proliferative and pro-apoptotic activities and might be useful in the clinical treatment of BPH.
Quisqualis indica (QI) has been used for treating disorders such as stomach pain, constipation, and digestion problem. This study was aimed to evaluate the therapeutic efficacy of QI extract on treating benign prostatic hyperplasia (BPH) in LNCaP human prostate cancer cell line and a testosterone-induced BPH rat model. LNCaP cells were treated with QI plus testosterone propionate (TP), and androgen receptor (AR) and prostate specific antigen (PSA) expression levels were assessed by Western blotting. To induce BPH, the rats were subjected to a daily subcutaneous injection of TP (3 mg/kg) for 4 wk. The rats in treatment group were orally gavaged with QI (150mg/kg) together with the TP injection. In-vitro studies showed that TP-induced increases in AR and PSA expression in LNCaP cells were reduced by QI treatment. In BPH-model rats, the prostate weight, testosterone in serum, DHT concentration and 5α-reductase mRNA expression in prostate tissue were significantly reduced following the treatment with QI. TP-induced prostatic hyperplasia and the expression of proliferating cell nuclear antigen (PCNA) and cyclin D1 were significantly attenuated in QI-treated rats. In addition, QI induced apoptosis by up-regulating caspase-3 and -9 activity and decreasing the B-cell lymphoma 2 (Bcl-2)/Bcl-2-associated X protein (Bax) ratio in prostate tissues of BPH rats. Further investigation showed that TP-induced activation of AKT and glycogen synthase kinase 3β (GSK3β) was reduced by QI administration. Therefore, our findings suggest that QI attenuates the BPH state in rats through anti-proliferative and pro-apoptotic activities and might be useful in the clinical treatment of BPH.
Keywords: Benign prostatic hyperplasia, Dihydrotestosterone, Quisqualis indica, Testosterone
Benign prostatic hyperplasia (BPH) is an age-related disease of unknown etiology, characterized by prostatic enlargement coincident with distinct alterations in tissue histology. In the present study, we investigated whether triptolide can prevent testosterone-induced prostatic hyperplasia in rats. Castration was performed via the scrotal route after urethane aesthesia. BPH was induced in experimental groups by daily subcutaneous injections of testosterone propionate (TP) for two weeks. Triptolide was administered daily by oral gavage at a dose of 100 and 50 μg·kg⁻¹ for 2 weeks, along with the TP injections. On day 14, the animals were humanely killed by cervical dislocation after aesthesia. Prostates were excised, weighed, and used for histological studies. Testosterone and dihydrotestosterone (DHT) levels in serum and prostate were measured. The results showed that triptolide significantly reduced the prostate weight, and the testosterone and DHT levels in both the serum and prostate. Histopathological examination also showed that triptolide treatment suppressed TP-induced prostatic hyperplasia. In conclusion, triptolide effectively inhibits the development of BPH induced by testosterone in a rat model.
Embelin, is a naturally occurring alkyl substituted hydroxyl benzoquinone and a major constituent from all the parts of Embelia ribes. It possesses antitumor, anti-inflammatory, antioxidant, analgesic activities and also has the ability to decrease testosterone levels. The present study was designed to determine the effect of embelin on testosterone-induced benign prostatic hyperplasia (BPH) in rats. Male Wistar rats were randomly divided into six groups and treated with either embelin (5 and 10 mg/kg), finasteride (1 mg/kg) or vehicle. After above mentioned treatment, testosterone (3 mg/kg; subcutaneously) was administration for 28 days, to induce BPH. On the day 29, blood samples were collected from the retro-orbital plexus. After blood sample collection, animals were sacrificed and prostates were immediately dissected out for weight measurement, biochemical estimations and histopathological studies. Prostatic serum acid phosphatase (PSAP) and prostate-specific antigen (PSA) were estimated. Administration of testosterone leads to significant increase in prosthetic weight, PSAP, PSA and lipid peroxidation levels and decrease in the antioxidant status. Moreover, histopathological abnormalities in the prostatic tissue were also found in these animals. Treatment with both the doses of embelin and finasteride significantly reversed the changes produced by testosterone. The authors conclude that antioxidant and anti-inflammatory properties of embelin are responsible for its protection against testosterone-induced BPH.
Objective:
To evaluate the efficacy of Bawu Decoction (, BWD, Palmul-tang in Korean) against benign prostatic hyperplasia (BPH).
Methods:
Twenty-four male Wistar rats were divided into 4 groups, with 6 rats in each group. The 4 study groups included sham-operated group (CON), BPH model group, fifinasteride-treated group, and BWD-treated group. All the groups except CON group received a subcutaneous injection of 10 mg/kg of testosterone, while CON group received saline. Finasteride at a dose of 5 mg/kg was administered to the finasteride-treated group for a period of 4 weeks. BWD group received BWD at a dose of 200 mg/kg for 4 weeks. The prostatic weight, prostate weight to body weight ratio, relative prostate weight ratio, serum testosterone and dihydrotestosterone (DHT) level, and histological analysis of prostatic tissue were analyzed.
Results:
Compared to BPH model group, BWD administration was associated with reductions in prostatic weight, prostate and relative prostate weight ratio weight to body weight ratio (P<0.05). The concentration of serum testosterone and DHT were higher in BPH group compared with CON group (P<0.05). Administration of finasteride and BWD suppressed the elevation of serum testosterone and DHT levels signifificantly (both P<0.05). In addition, BWD suppressed the growth of prostatic tissue (P<0.05).
Conclusion:
BWD has suppressant effects on development of BPH through inhibition of serum testosterone and DHT.
A plethora of complementary and alternative medicine (CAM) interventions, primarily dietary supplements, have been utilized in some preliminary clinical trials that have demonstrated an ability to reduce the symptoms of benign prostatic hyperplasia/lower urinary tract symptoms (BPH/LUTS). However, the one supplement that arguably had the most positive data in the history of urology was saw palmetto, but compared to placebo in two separate definitive North American clinical trials dosages of 320–960 mg over 18 months, it proved to work no better than placebo, which somewhat contradicts the positive findings that occurred in several European trials of a standardized trademarked saw palmetto extract known as Permixon (Pierre Fabre, Castres, France) and other products. Currently, two dietary supplements have consistent older (no recent supportive trials) positive meta-analysis data compared to placebo—beta-sitosterol and pygeum (endangered herbal list in some geographic areas). Several supplements have preliminary positive clinical data; these include cernilton, pumpkin seed oil, and, to a lesser extent, stinging nettle. Some supplements have no efficacy or may even be harmful and encourage the growth of BPH, including high-dose (80 mg or higher) zinc supplements, based on some clinical and observational data. BPH prescription medications are arguably more rapidly effective compared to any dietary supplement, but the benefit-to-risk ratio or side effect profile and, at times, cost arguably favor some supplements over prescription medications along with lifestyle changes for mild to moderate BPH, or some patients could theoretically use both a prescription and CAM agent without much concern over drug interactions. Heart-healthy lifestyle changes should be stressed to improve BPH/LUTS and overall health outcomes and to improve the efficacy of BPH medications. Any supplement recommended for BPH should be cost-effective/competitive and have a heart-healthy profile (also known as the first-do-no-harm approach).
INTRODUCTION: D004, an promissory active ingredient in treatment and prevention of begnin prostatic hyperplasia, is obtained from the fruit oil of Roystonea regia (Kunth) O.F. Cook. It is composed by a mixture of free fatty acids including lauric and myristic acids, both very important by their pharmacological effects. OBJECTIVE: to determine the potential influence of harvest season on the oily content and the concentration of lauric and myristic acids from R. regia fruits. METHODS: each month for two years, it was possible to collect mature fruits from R. regia in a selected group. In dry and milled samples it was determined the oily content in a gravimetric way and that of fatty acids by gas chromatography. RESULTS: there were differences statistically significant in oily contents and of lauric and myristic acids; however, the contents determined in all the cases remained within the quality specifications established for the plant material. CONCLUSIONS: the plant material collected for all the year may be used in obtaining of R. regia oil, raw material used in the production of D004.
Introduction: Dietary supplements and nutraceuticals are used variously for protection from ED, decreased libido, BPH and prostate carcinoma by men for centuries. But we encounter some problems in their forms, marketings and instructions. In the literature we see that there are controversies about usage of most supplements on the market. Furthermore, unknown contents of these supplements, besides this there are pharmaceuticals in some supplements (PDE5 inhibitors etc.) and illegally marketings are contradictory conditions. In this article, we try to mention about andrological usage of dietary supplements, their effects, side effects and the problems with these products.
In this paper, midrib of coconut palm leaves (MCL) was investigated for the purpose of development of natural fiber reinforced polymer matrix composites. A new natural fiber composite as MCL/polyester is developed by the hand lay-up method, and the material and mechanical properties of the fiber, matrix and composite materials were evaluated. The effect of fiber content on the tensile, flexu-ral, impact, compressive strength and heat distortion temperature (HDT) was investigated. It was found that the MCL fiber had the maximum tensile strength, tensile modulus flexural strength, flexural modulus and Izod impact strength of 177.5MPa, 14.85GPa, 316.04MPa and 23.54GPa, 8.23KJ/m2 respectively. Reinforcement of MCL enhanced the mechanical properties of pure polyester, including that of tensile strength (by 26%), tensile modulus (by 356%), flexural strength (by 41.81%), flexural modulus (by 169%) and Izod impact strength (by 23 times), but the com-pressive strength was adversely affected. HDT decreased due to fiber loading, but increased with weight fraction of fiber content. Moreover, the experimental results were compared with theoretical model (Rule of mixture) and other natural fiber/polyester composites.
The present study was designed to investigate the effect of crude bark extract of Oroxylum indicum in experimental
prostatic hyperplasia in rat. The male animals were treated either corn oilror testosterone (10 mgkg-l) dissolved in corn oil and
testosterone with crude bark extracts of Oroxylum indicum (SO
"rrd
100 mgkg-r) consecutively for three weeks. The protective
ef8cary o{ Oroxylum indicum on prostate hyperplasia was illustrated by prostate weight, prostatic index, percentage of
inhibition and histological examinations. Crude extract of Ororylum indicum caused signiftcant reduction in the prostate
weight and prostatic index when compared to testosterone induced BPH model group. Crude extract treated group also
ameliorated the hypelplasia of prostate epithelium in a similar manner as was observes in finasteride (5 ngkg-f ) treated
group. The study indicatesthat OroSrlum indicum signiffcantly reduced the progression of BPH and it maybe an another
phytotherapeutial source of drugs in BPH treatment.
Coconut palm probably derives from Polynesia or Asia. The variety of coconut products in Poland includes fruit of the coconut, desiccated coconut, oil, water, milk, sugar and coconut flour. Over the years, coconut products are becoming more and more popular. Their import and consumption in Poland are increasing. Coconut products have also many health benefits. They have anti-inflammatory, antitumor and hepatoprotective properties. The aim of this paper is to review the literature on changes in the market of vegetable fats in Poland in recent years and the variety and health properties of various coconut products.
Pueraria mirifica (PM) extract contains phytoestrogen daidzein and genistein. In this study, we investigated the protective effect of PM extract, daidzein and genistein on a testosterone-induced prostatic hyperplasia in rats. Testosterone was administered at 3 mg kg−1 to rats followed by the PM extract, daidzein and genistein for a period of 30 days with finasteride as positive control. The testosterone level was increased, indicating inhibition of 5α-reductase converting testosterone to dihydrotestosterone. This was confirmed by prostate-specific antigen level that significantly decreased when treated with PM extract, daidzein and genistein. The PM extract, daidzein and genistein reduced the increase in the prostate/body weight ratio in testosterone-induced rats. This gives indication that PM extract, daidzein and genistein possessed protective activity for the treatment of benign prostatic hyperplasia. The analysis of histoarchitechture of the prostate has also shown that there was a significant improvement in prostatic cells of the testosterone-induced rats when treated with PM extract, daidzein and genistein.
In this paper, we reviewed plants being effective in treatment of BPH for the purpose of finding new sources of pharmaceutical agents.
All pertinent literature databases were searched. The search keywords were plant, herb, herbal therapy, phytotherapy, benign prostatic hyperplasia, BPH, and prostate. All of the human, animal and in vitro studies were evaluated.
According to the studies, some of the substantial effective constituents of the plants in treatment of BPH are oenothein B, icaritin, xanthohumol, diarylheptanoid, 2,6,4'-trihydroxy-4-methoxybenzophenone, emodin, fatty acids, atraric acid, n-butylbenzene-sulfonamide, curbicin, theaflavin-3,30-digallate, penta-O-galloyl-b-D-glucose, lycopene, sinalbin, β-sitosterol, secoisolariciresinol diglucoside, genistein, apigenin, baicalein, and daidzein. Besides, Serenoa repens, Pygeum africanum, Curcubita pepo, and Urtica dioica as the most prevalent plants used to treat BPH. S. repens in human studies showed equivalent effectiveness to tamsulosin and in combination to U. dioica revealed equal effects to finastride with less side effects.
There are numerous plants that have beneficial influence on BPH although the mechanisms of action in some plants are not well understood yet. Active ingredients of some of these plants are known and can be used as lead components for development of new effective and safe drugs.
INTRODUCTION: D004, an promissory active ingredient in treatment and prevention of begnin prostatic hyperplasia, is obtained from the fruit oil of Roystonea regia (Kunth) O.F. Cook. It is composed by a mixture of free fatty acids including lauric and myristic acids, both very important by their pharmacological effects. OBJECTIVE: to determine the potential influence of harvest season on the oily content and the concentration of lauric and myristic acids from R. regia fruits. METHODS: each month for two years, it was possible to collect mature fruits from R. regia in a selected group. In dry and milled samples it was determined the oily content in a gravimetric way and that of fatty acids by gas chromatography. RESULTS: there were differences statistically significant in oily contents and of lauric and myristic acids; however, the contents determined in all the cases remained within the quality specifications established for the plant material. CONCLUSIONS: the plant material collected for all the year may be used in obtaining of R. regia oil, raw material used in the production of D004.
Benign prostatic hyperplasia (BPH) is a noncancerous growth of the prostate gland resulting due to over-proliferation of the stromal and glandular elements of the prostate and is associated with lower urinary tract symptoms. Natural products, containing inherently vast structural diversity than synthetic compounds, have been the major resources of bioactive agents and will continue to play as protagonists for discovering new drugs. Phytotherapeutic products have been used traditionally in developing countries while the use of them as complementary alternative medicine is increasing rapidly in developed countries for the management of BPH. Although mono preparations (single plant only) are available, many industries manufacture combination products (plant extracts) in an attempt to provide enhanced efficacy to improve marketability, and to provide their own "unique" product that can be registered, because these products have no patent protection. The mechanism of action of the phytotherapeutic agents is not clearly understood as many in vitro experimental studies have demonstrated diverse spectrum of mechanisms. The main mechanisms of action that has received the greatest attention are anti-inflammatory, 5α-reductase inhibition, and more recently growth factor alteration. The current review covers all such studies and critiques the efficacy and value of such phytotherapeutic products and preparations available for the management of BPH.
Benign prostate hyperplasia (BPH) is the most common proliferative disorder affecting older men and results in prostate enlargement and lowered urinary tract symptoms. Jaeumganghwa-tang (JGT), an oriental traditional herbal formula, has been used in China (Zi-yin-jiang-huo-tang in Chinese), Japan (Jiin-koka-to in Japanese), and Korea for many years. Effects of JGT on prostate dihydrotestosterone (DHT) level and prostatic hyperplasia were investigated using a rat model, in which BPH was induced using testosterone propionate (TP). Rats were divided into five groups. One group was used as a normal, and four groups received subcutaneous injections of TP for 4 weeks to induce BPH. JGT (200 or 400 mg/kg) was administered daily for 4 weeks by oral gavage concurrently with TP injections, and rats were sacrificed at scheduled times. Prostates were weighed, and histopathologic examination was conducted. DHT levels in serum and the prostate were measured, and the expression of proliferating cell nuclear antigen (PCNA) protein was investigated using Western blotting. BPH animals showed increases in absolute and relative weights of the prostate, levels of DHT in serum and the prostate, and expression of PCNA in the prostate, whereas JGTtreated animals showed significant reductions in these indices compared with the BPH animals. Administration of JGT attenuated TP-induced epithelial hyperplasia. These findings indicate that JGT inhibits the development of BPH, an effect closely associated with a reduction in DHT level.
Human prostate was used as a source of 5α reductase. Compounds were incubated with an enzyme preparation and [3H]testosterone. [3H]-dihydrotestosterone production was measured to calculate 5ã reductase activity. IC50 values (ng/ml) were finasteride = 1; Permixon = 5,600; Talso = 7,000; Strogen Forte = 31,000; Prostagutt = 40,000; and Tadenan = 63,000. Bazoton and Harzol had no activity at concentrations up to 500,000 ng/ml. In castrate rats stimulated with testosterone (T) or dihydrotestosterone (DHT), finasteride, but not Permixon or Bazoton, inhibited T stimulated prostate growth, while none of the three compounds inhibited DHT stimulated growth. These results demonstrate that finasteride inhibits 5α reductase, while Permixon and Bazoton have neither anti-androgen nor 5α reductase inhibitory activity. In addition, in a 7 day human clinical trial, finasteride, but not Permixon or placebo, decreased serum DHT in men, further confirming the lack of 5α reductase inhibition by Permixon. Finasteride and the plant extracts listed above do not inhibit the binding of DHT to the rat prostatic androgen receptor (concentrations to 100 μg/ml). Based on these results, it is unlikely that these plant extracts would shrink the prostate by inhibiting androgen action or 5α reductase. © 1993 Wiley-Liss, Inc.
The physical and chemical properties of the oil extracted from six (6) varieties of coconut fruits were determined. The oils were brownish, some yellowish when melted, and at times white when solidified. The oils had specific gravity ranging between 0.90 and 0.92. The yield of the oil (% contents) from the ether extract was also analyzed using soxhlet extraction technique. The results showed the oil contents of 88.54% in dry samples and 69.14% in fresh samples. Result of the findings showed a higher percentage of saturated fatty acid content across the entire samples (88.5?0.85% - 97.0?0.37%) in the dry samples, than the unsaturated fatty acid constituents (8.4?0.45% - 9.5?0.30%). The moisture content was higher in the fresh samples than the dry samples. These findings therefore suggest a high percentage oil yield in the dry samples. It is therefore advisable that the nuts be harvested dry if the oil is intended for commercial use.
The aim of this study was to determine the effect of the phytotherapeutic agent, Permixon, on a novel coculture model of benign prostatic hyperplasia (BPH) in an effort to better understand the mode of action of the drug in vivo.
The effect of Permixon, at the calculated therapeutic concentration, on the activity of 5alpha-reductase isoenzymes was evaluated utilizing a pH-specific assay. Prostate-specific antigen (PSA) secretions into the medium were measured in the presence and absence of Permixon and quantified by an ELISA assay. The morphological patterns before and following Permixon treatment were also examined by electron microscopy. All results were compared to controls.
Permixon at a concentration of 10 micrograms/ml (calculated plasma concentration in patient receiving recommended therapeutic dosage) was shown to be an effective inhibitor of both 5alpha-reductase types I and II isoenzymes without influencing the secretion of PSA by the epithelial cells, even after stimulation with testosterone. The morphology of Permixon-treated cells was found to be markedly different from that of untreated controls. Cells which had been treated with the drug demonstrated extensive accumulation of lipids in the cytoplasm and widespread damage of intracellular membranes, including mitochondrial and nuclear membranes.
Permixon is an effective dual inhibitor of 5alpha-reductase isoenzyme activities in the prostate. Unlike other 5alpha-reductase inhibitors, Permixon induces this effect without interfering with the cells' capacity to secrete PSA, thus permitting the continued use of PSA measurements for prostate cancer screening.
The link between excessive consumption of dietary saturated fats and coronary heart disease (CHD) is now well established. Because of its high content of saturated fatty acids, the consumption of foods containing coconut oil may therefore be a risk factor for CHD. While the fatty acid composition of coconut oil is well established, relatively little is known about the other constituents of coconut: the milk, water, cream and meat fractions. In this study, we show that while the water fraction is low in lipid content, the milk contains about 24% of the fat content of oil and the cream and meat fractions about 34%. The other coconut constituents contain significant amounts of medium-chain triglycerides that are formed from fatty acids of chain length 8:0 to 14:0. It is these fatty acids, primarily 14:0, that are thought to be atherogenic. On the other hand, medium-chain triglycerides may be advantageous under some circumstances in that they are absorbed intact and do not undergo degradation and re-esterification processes. As a result, medium-chain triglycerides provide a ready source of energy and may be useful in baby foods or in diet therapy. Nevertheless, the possible negative effects of the saturated fatty acids and the absence of the essential fatty acid linolenic acid from all coconut constituents suggest that the coconut milk, oil and cream should not be used on a regular basis in adults.
Prostane, a polyherbal formulation, was evaluated for its efficacy on 5alpha-reductase inhibition, alpha-adrenergic antagonistic activity and testosterone-induced prostatic hyperplasia.
5alpha-reductase inhibition was evaluated using rat prostate homogenate as an enzyme source. Adrenergic antagonistic activity was evaluated using isolated rat vas deferens. Experimental prostatic hyperplasia was induced in rats by giving testosterone 3 mg/kg sc for 21 days.
Prostane dose-dependently inhibited 5alpha-reductase activity and exhibited alpha-adrenergic antagonistic activity. Treatment with Prostane at 250, 500 and 750 mg/kg body wt, po for 21 days significantly reduced the prostatic weight, the epithelial height and the stromal proliferation in experimental prostatic hypertrophy.
Prostane is effective in the treatment of experimental prostatic hypertrophy in rats and may be passed on to clinical trials on benign prostatic hypertrophy after necessary toxicological evaluations.
Objective:
The development of the human benign prostatic hyperplasia clearly requires a combination of testicular androgens and aging. Although the role of androgens as the causative factor for human benign prostatic hyperplasia is debated, they undoubtedly have at least a permissive role. The principal prostatic androgen is dihydrotestosterone (DHT). Although not elevated in human benign prostatic hyperplasia, DHT levels in the prostate remain at a normal level with aging, despite a decrease in the plasma testosterone.
Results:
DHT is generated by reduction of testosterone. Two isoenzymes of 5alpha-reductase have been discovered. Type 1 is present in most tissues of the body where 5alpha-reductase is expressed and is the dominant form in sebaceous glands. Type2 5alpha-reductase is the dominant isoenzyme in genital tissues, including the prostate. Finasteride is a 5alpha-reductase inhibitor that has been used for the treatment of benign prostatic hyperplasia and male-pattern baldness. At doses used clinically, its major effect is through suppression of type 2 5alpha-reductase, because it has a much lower affinity for the type 1 isoenzyme. Finasteride suppresses DHT by about 70% in serum and by as much as 85-90% in the prostate. The remaining DHT in the prostate is likely to be the result of type 1 5alpha-reductase. Suppression of both 5alpha-reductase isoenzymes with GI198745 result in greater and more consistent suppression of serum dihydrotestosterone than that observed with a selective inhibitor of type 2 5alpha-reductase. Physiological and clinical studies comparing dual 5alpha-reductase inhibitors, such as GI198745, with selective type 2, such as finasteride, will be needed to determine the clinical relevance of type 1 5alpha-reductase within the prostate. Two large international multicenter, phase III trials have been published documenting the safety and efficacy of finasteride in the treatment of human benign prostatic hyperplasia. Combining these two studies, randomized, controlled data are available for 12 months. Noncontrolled extension of these data from a subset of patients, who elected to continue drug treatment for 3, 4 or 5 years, are also available. Long-term medical therapy with finasteride can reduce clinically significant endpoints such as acute urinary retention or surgery. According to the meta-analysis of six randomised clinical trial with finasteride, finasteride is most effective in men with large prostates. A more effective dual inhibitor of type 1 and 2 human 5alpha-reductase may lower circulating DHT to a greater extent than finasteride and show advantages in the treatment of human benign prostatic hyperplasia and other disease states that depend on DHT.
Conclusion:
Clinical evaluation of potent dual 5alpha-reductase inhibitors may help define the relative roles of human type 1 and 2 5alpha-reductase in the pathophysiology of benign prostatic hyperplasia and other androgen-dependent diseases.
The phytotherapeutic agent Serenoa repens is an effective dual inhibitor of 5alpha-reductase isoenzyme activity in the prostate. Unlike other 5alpha-reductase inhibitors, Serenoa repens induces its effects without interfering with the cellular capacity to secrete PSA. Here, we focussed on the possible pathways that might differentiate the action of Permixon from that of synthetic 5alpha-reductase inhibitors. We demonstrate that Serenoa repens, unlike other 5alpha-reductase inhibitors, does not inhibit binding between activated AR and the steroid receptor-binding consensus in the promoter region of the PSA gene. This was shown by a combination of techniques: assessment of the effect of Permixon on androgen action in the LNCaP prostate cancer cell line revealed no suppression of AR and maintenance of PSA protein expression at control levels. This was consistent with reporter gene experiments showing that Permixon failed to interfere with AR-mediated transcriptional activation of PSA and that both testosterone and DHT were equally effective at maintaining this activity. Our results demonstrate that despite Serenoa repens effective inhibition of 5alpha-reductase activity in the prostate, it did not suppress PSA secretion. Therefore, we confirm the therapeutic advantage of Serenoa repens over other 5alpha-reductase inhibitors as treatment with the phytotherapeutic agent will permit the continuous use of PSA measurements as a useful biomarker for prostate cancer screening and for evaluating tumour progression.
Saw palmetto is used by over 2 million men in the United States for the treatment of benign prostatic hyperplasia and is commonly recommended as an alternative to drugs approved by the Food and Drug Administration.
In this double-blind trial, we randomly assigned 225 men over the age of 49 years who had moderate-to-severe symptoms of benign prostatic hyperplasia to one year of treatment with saw palmetto extract (160 mg twice a day) or placebo. The primary outcome measures were changes in the scores on the American Urological Association Symptom Index (AUASI) and the maximal urinary flow rate. Secondary outcome measures included changes in prostate size, residual urinary volume after voiding, quality of life, laboratory values, and the rate of reported adverse effects.
There was no significant difference between the saw palmetto and placebo groups in the change in AUASI scores (mean difference, 0.04 point; 95 percent confidence interval, -0.93 to 1.01), maximal urinary flow rate (mean difference, 0.43 ml per minute; 95 percent confidence interval, -0.52 to 1.38), prostate size, residual volume after voiding, quality of life, or serum prostate-specific antigen levels during the one-year study. The incidence of side effects was similar in the two groups.
In this study, saw palmetto did not improve symptoms or objective measures of benign prostatic hyperplasia. (ClinicalTrials.gov number, NCT00037154.).
The effects of high and low fat diets with identical polyunsaturated/saturated fatty acid (P/S) ratios on plasma postprandial levels of some hemostatic variables and on fasting lipoprotein (a) [Lp(a)] are not known. This controlled crossover study compared the effects of a high fat diet [38.4% of energy (E%) from fat; HSAFA-diet, P/S ratio 0.14], a low fat diet (19.7 E% from fat; LSAFA-diet, P/S ratio 0.17), both based on coconut oil, and a diet with a high content of monounsaturated fatty acids (MUFA) and PUFA (38.2 E% from fat; HUFA-diet, P/S ratio 1.9) on diurnal postprandial levels of some hemostatic variables (n = 11) and fasting levels of Lp(a) (n = 25). The postprandial plasma concentration of tissue plasminogen activator antigen (t-PA antigen) was decreased when the women consumed the HSAFA-diet compared with the HUFA-diet (P = 0.02). Plasma t-PA antigen was correlated with plasminogen activator inhibitor type 1 (PAI-1) activity when the participants consumed all three diets (Rs = 0.78, P < 0.01; Rs = 0.76, P < 0.01; Rs = 0.66, P = 0.03; on the HSAFA-, the LSAFA- and the HUFA-diet, respectively), although the diets did not affect the PAI-1 levels. There were no significant differences in postprandial variations in t-PA activity, factor VII coagulant activity or fibrinogen levels due to the diets. Serum fasting Lp(a) levels were lower when women consumed the HSAFA-diet (13%, P < 0.001) and tended to be lower when they consumed the LSAFA-diet (5.3%, P = 0.052) than when they consumed the HUFA-diet. Serum Lp(a) concentrations did not differ when the women consumed the HSAFA- and LSAFA-diets. In conclusion, our results indicate that a coconut oil-based diet (HSAFA-diet) lowers postprandial t-PA antigen concentration, and this may favorably affect the fibrinolytic system and the Lp(a) concentration compared with the HUFA-diet. The proportions of dietary saturated fatty acids more than the percentage of saturated fat energy seem to have a beneficial influence on Lp(a) levels.
The genesis of benign prostate hyperplasia (BPH) depends on two factors: testicular androgen and the aging process. The most important androgen in the prostate is dihydrotestosterone (DHT). In the aging male the level of DHT in the prostate remains largely constant although the plasma level of testosterone decreases.
DHT is formed by the reduction of testosterone by the enzyme 5-α-reductase, which has two isoenzymes. The 5-α-reductase type 2 is the predominant isoenzyme in genital tissue and thus also in the prostate. Finasteride is a 5-α-reductase inhibitor, which is applied in the treatment of BHP and male baldness. In the doses used finasteride acts mainly by inhibiting the 5-α-reductase type 2, thereby reducing the serum level of DHT by approximately 70% and by about 85–90% in the prostate. Indeed the effect of finasteride in BPH was proven in clinical studies. However, the circulating and intraprostatic DHT could be further reduced by a more effective dual 5-α-reductase inhibitor, which would be efficacious in the treatment of benign prostate hyperplasia and other DHT-related disorders.
Medical treatment for the symptoms of benign prostatic hyperplasia (BPH) consists of α blockers and 5-α-reductase inhibitors.
Data suggest that 5-α-reductase inhibitors can prevent progression of BPH and reduce the risk of BPH-related surgery, especially
in men with large-volume prostates. Results from the largest randomized, prospective, placebo-controlled trial, the Medical
Therapy of Prostatic Symptoms trial, have been presented. These results support the notion of using 5-α-reductase inhibitors
for the prevention of BPH progression and BPH-related surgery. Furthermore, long-term 5-α-reductase inhibitor monotherapy,
although slow in onset, is a viable therapy for symptom relief in men with mild to moderate symptoms.
Background:
Benign prostatic hypertrophy is the nonmalignant, uncontrolled growth of prostatic epithelial cells and stroma that, left untreated, may lead to difficult urination and other complications. A common treatment of BPH is lipid extract from saw palmetto fruit, and lipid extract from Cuban Royal palm (a palm of the same family) fruit is being studied for this use. One study found that the latter, D-004, at 100 to 400 mg/kg daily prevented prostatic hypertrophy (PH) induced with testosterone (T) in a rat model.
Objectives:
This study comprised 2 experiments in a rat model. The first assessed the effects of different doses of D-004 on T-induced PH; the second investigated the effects of D-004 on PH induced with dihydrotestosterone (DHT).
Methods:
In experiment 1, rats were distributed in 6 groups of 10 rats each. One group received an SC injection of soy oil and oral treatment with Tween 65/water vehicle (negative control). The other 5 groups received an SC injection of T 3 mg/kg daily and oral treatment with vehicle (positive control) or D-004 at 50, 200, 400, or 800 mg/kg daily suspended in vehicle. In experiment 2, rats were distributed in 3 groups of 10 rats each. A negative control group received treatment as in experiment 1. Positive controls received an SC injection of DHT 1.5 mg/kg and vehicle orally. The third group received an SC injection of DHT and oral treatment with D-004 at 800 mg/kg suspended in vehicle. All treatments were given for 14 days. At sacrifice, prostates were removed and weighed. Mean prostatic weights and prostatic/body weight ratios were calculated.
Results:
In experiment 1, in the groups receiving D-004 at 200, 400, or 800 mg/kg daily, prostatic weight was significantly lower compared with the positive control group (P < 0.05, P < 0.01, and P < 0.001, respectively); this effect was not seen in the group receiving 50 mg/kg daily. In the groups receiving D-004 at 400 and 800 mg/kg daily, prostatic/body weight ratio was significantly lower compared with positive controls (both, P < 0.05); this effect was not seen in the groups receiving 50 or 200 mg/kg daily. In experiment 2, prostatic weight and prostatic/body weight ratio in the group receiving D-004 were similar to those of positive controls. Body weight was not affected in any of the groups receiving D-004.
Conclusions:
This study of rats with T- or DHT-induced PH suggests that D-004 at 200 to 800 mg/kg daily administered orally prevents T-induced PH, and that D-004 at 800 mg/kg daily does not prevent DHT-induced PH.
The inhibition of testosterone 5oc-reductase (EC 1.3.99.5) (5αR) in vitro by lipophilic extracts from Sabal serrulata fruits effective on Benign Prostatic hyperplasia (BPH) treatment is due entirely to free fatty acid content. In order to find out structure-inhibition activity relationships of the action of free fatty acids on the enzyme, we investigated the influences of chain-length, esterification, saturation degree, and oxidation on fatty acid 5aR inhibition activity. For fatty acid-like 5αR inhibition a strongly polar end-group and a molecular skeleton allowing nonpolar interactions with the enzyme are required. 5αR activity in prostate tissue may be influenced by lipid environment.
α1-adrenoceptors are most important in the human cardiovascular system in the vasulature. The subtype(s) mediating vasoconstriction in humans have not yet been firmly identified, but the radioreceptor assay appears to be a promising approach. Three subtypes of α1-adrenoceptors have been defined in pharmacological and molecular terms and are designated α1A, α1B, and α1D. However, some data are not fully explained by these classifications, indicating the possible existence of additional subtypes. In particular, the low apparent affinity of prazosin in some functional assays has led to the proposal of an α1-adrenoceptor subtype with low prazosin affinity, which has been designated α1. This article focuses on radioligand binding and functional data of the three α1-adrenoceptor subtypes. α1-Adrenoceptors mediate numerous effects in the cardiovascular and urogenital systems. In the human lower urinary tract, α1-adrenoceptors mediate smooth-muscle contraction of bladder neck, urethra, and prostate. In the human prostate, the α1A-adrenoceptor dominates at the protein level and probably is also most important for contraction. Low apparent affinities of some antagonists in functional tests with human prostate do not necessarily contradict the α1A-adrenoceptor hypothesis but may relate to assay conditions.
Die Arbeit beschreibt den Aufbau und die Funktion des sympathischen Nervensystems, welches über Kontrolle des glattmuskulären Tonus den urethralen Widerstand regulieren kann. Funktionelle Untersuchungen konnten α1- und speziell α1A-Adrenozeptoren sowie den Neurotransmitter Noradrenalin für die Tonusregulation identifizieren. Durch selektive pharmakologische Hemmung der α1-Adrenozeptoren kann der urethrale Widerstand reduziert werden, was mit den Substanzen Alfuzosin, Doxazosin, Terazosin und Tamsulosin möglich ist. Es führt zur Verbesserung der subjektiven Symptomatik (20–65%) sowie der Harnstrahlstärke (1–4,3 ml/s) bei Patienten mit BPH unabhängig von der Ausprägung der initialen Miktionssymptomatik, dem Grad der infravesikalen Obstruktion oder der Prostatagröße.
Eine signifikante Restharnsenkung wird nur gelegentlich beobachtet. Die Inzidenz eines akuten Harnverhalts kann jedoch durch Alfuzosin signifikant vermindert werden. Im Einzelnen werden 39 randomisierte, placebokontrollierte, doppelblinde Studien dieser 4 α1-Rezeptorblocker mit insgesamt 14.924 Patienten sowie Vergleichsstudien zwischen den α1-Rezeptorblockern, Phytopharmaka und Finasterid vorgestellt.
Alle α1-Rezeptorblocker sind hinsichtlich ihrer Wirkung gleich potent, Alfuzosin und Tamsulosin zeigen aber eine geringere Häufigkeit von Nebenwirkungen als Doxazosin oder Terazosin. Die durch Doxazosin oder Terazosin ausgelöste Vasodilatation wurde früher zur Hypertoniebehandlung eingesetzt, jedoch heute wegen einer erhöhten Inzidenz kardialer Komplikationen nicht mehr für diese Indikation empfohlen (ALLHAT-Studie). Die Verbesserung von Symptomatik und Harnstrahlstärke ist bei α1-Rezeptorblockern ausgeprägter als bei Phytopharmaka oder Finasterid, weshalb α1-Rezeptorblocker die Therapie der 1. Wahl bei symptomatischen BPH-Patienten ohne oder mit nur geringer infravesikaler Obstruktion sind.
Human or rat microsomal 5 alpha-reductase activity, as measured by enzymic conversion of testosterone into 5 alpha-dihydrotestosterone or by binding of a competitive inhibitor, [3H]17 beta-NN-diethulcarbamoyl-4-methyl-4-aza-5 alpha-androstan-3-one ([3H]4-MA) to the reductase, is inhibited by low concentrations (less than 10 microM) of certain polyunsaturated fatty acids. The relative inhibitory potencies of unsaturated fatty acids are, in decreasing order: gamma-linolenic acid greater than cis-4,7,10,13,16,19-docosahexaenoic acid = cis-6,9,12,15-octatetraenoic acid = arachidonic acid = alpha-linolenic acid greater than linoleic acid greater than palmitoleic acid greater than oleic acid greater than myristoleic acid. Other unsaturated fatty acids such as undecylenic acid, erucic acid and nervonic acid, are inactive. The methyl esters and alcohol analogues of these compounds, glycerols, phospholipids, saturated fatty acids, retinoids and carotenes were inactive even at 0.2 mM. The results of the binding assay and the enzymic assay correlated well except for elaidic acid and linolelaidic acid, the trans isomers of oleic acid and linoleic acid respectively, which were much less active than their cis isomers in the binding assay but were as potent in the enzymic assay. gamma-Linolenic acid had no effect on the activities of two other rat liver microsomal enzymes: NADH:menadione reductase and glucuronosyl transferase. gamma-Linolenic acid, the most potent inhibitor tested, decreased the Vmax. and increased Km values of substrates, NADPH and testosterone, and promoted dissociation of [3H]4-MA from the microsomal reductase. gamma-Linolenic acid, but not the corresponding saturated fatty acid (stearic acid), inhibited the 5 alpha-reductase activity, but not the 17 beta-dehydrogenase activity, of human prostate cancer cells in culture. These results suggest that unsaturated fatty acids may play an important role in regulating androgen action in target cells.
We previously suggested [Steroids33, (1979) 3; Steroids37, (1981) 6] that cultured genital skin fibroblasts should prove useful for screening of potential antiandrogens in human and living target cells. “Serenoa repens” lipidic extract (S.R.E.) was recently reported (Br. J. Pharmacoi., in press) to inhibit androgen action in animals. The present investigation was designed to study the antiandrogenicity of this compound in human cells: we therefore analyzed the effects of S.R.E. on the intracellular conversion of testosterone (T) to 5α-reduced derivatives, and we investigated interaction of S.R.E. with the intracellular androgen-receptor complex. Since the chemical structure of the active component of S.R.E. is still unknown, results are expressed in U/ml (one unit is defined as the amount of S.R.E. required to inhibit 50% of the specific binding (IC50) of [³H]1881 to rat prostate cytosol).
Extract from fruit of Sabal serrulata are used in the treatment of human benign prostate hyperplasia (BPH). Therefore, it is of interest whether this phytopharmacon has any influence on the androgen metabolism in the human prostate. It was found that the extract IDS 89 of Sabal serrulata inhibited dose dependently 5 alpha-reductase activity in the epithelium and stroma of human BPH, the mean inhibition being 29% and 45%, respectively. This inhibitory effect is mainly due to the saponifiable subfraction of IDS 89 showing a mean 5 alpha-reductase inhibition of 39% and 38% in epithelium and stroma, respectively. The inhibition was dose dependent and noncompetitive. At a testosterone concentration of 580 nM as substrate for 5 alpha-reductase, the main fatty acids of the extract IDS 89 gave rise to a percentual enzyme inhibition in the epithelium and stroma as follows: 51% and 42% (lauric acid), 5% and 0% (oleic acid), 43% and 34% (myristic acid), 2% and 0% (palmitic acid), respectively. The inhibitory effect of lauric acid was noncompetitive and dose dependent up to a concentration of 0.2 nM, the maximal inhibition in the epithelium and stroma being 52% and 45%, respectively. The nonsaponifiable subfraction, consisting mainly of phytosterols, showed a mean inhibition of 5 alpha-reductase in the epithelium and stroma of 15% and 10%, respectively. Finally, the hydrophilic subfraction, containing carbohydrates, amino acids, and polysaccharides, showed no inhibitory effect. The present in vitro studies suggest that the Sabal serrulata extract IDS 89 has an inhibitory effect on 5 alpha-reductase in the epithelium and stroma of human BPH. This inhibition is mainly due to the fatty acids of the saponifiable subfraction.
Controversy regarding the relative efficacy of treatments for the relief of the symptoms of benign prostatic hyperplasia (BPH).
This was a 6-month double-blind randomized equivalence study that compared the effects of a plant extract (320 mg Permixon) with those of a 5 alpha-reductase inhibitor (5 mg finasteride) in 1,098 men with moderate BPH using the International Prostate Symptom Score (IPSS) as the primary end-point.
Both Permixon and finasteride decreased the IPSS (-37% and -39%, respectively), improved quality of life (by 38 and 41%), and increased peak urinary flow rate (+25% and +30%, P = 0.035), with no statistical difference in the percent of responders with a 3 ml/sec improvement. Finasteride markedly decreased prostate volume (-18%) and serum PSA levels (-41%); Permixon improved symptoms with little effect on volume (-6%) and no change in PSA levels. Permixon fared better than finasteride in a sexual function questionnaire and gave rise to less complaints of decreased libido and impotence.
Both treatments relieve the symptoms of BPH in about two-thirds of patients but, unlike finasteride, Permixon has little effect on so-called androgen-dependent parameters. This suggests that other pathways might also be involved in the symptomatology of BPH.
Serenoa repens (Permixon) has been available for several years for the treatment of men with benign prostatic hyperplasia (BPH). The drug is the n-hexane lipidosterolic extract of the dwarf American palm (also known as Serenoa repens) and is a complex mixture of various compounds. A number of pharmacodynamic effects have been demonstrated with the lipidosterolic extract of Serenoa repens (LSESR), suggesting multiple mechanisms of action including in vitro inhibition of both type 1 and type 2 isoenzymes of 5 alpha-reductase and interference with binding of dihydrotestosterone to cytosolic androgen receptors in prostate cells. In controlled clinical trials in men with BPH, oral administration of Serenoa repens 160 mg twice daily for 1 to 3 months was generally superior to placebo in improving subjective symptoms, such as dysuria, as well as objective parameters. The frequency of nocturia was reduced by 33 to 74%, while urinary frequency during the day decreased by 11 to 43% and peak urinary flow rate increased by 26 to 50% with Serenoa repens. Corresponding values for placebo were 13 to 39%, 1 to 29% and 2 to 35%. The only large comparative trial conducted to date, in which > 1000 men with moderate BPH were randomised to receive Serenoa repens 160 mg twice daily or finasteride 5 mg once daily for 6 months, demonstrated similar efficacy between the two drugs. No statistically significant difference was demonstrated between treatment groups for improvement in patient self-rated quality-of-life scores and the primary end-point of objective symptom score; International Prostate Symptom Score improved by 37% with Serenoa repens compared with 39% with finasteride. In much smaller comparative trials, few significant differences were demonstrated between Serenoa repens and alpha 1-receptor antagonists, and larger randomised trials of adequate duration are required to better compare the clinical efficacy of these drugs. The most frequently reported adverse events in clinical trials with Serenoa repens have been minor gastrointestinal problems (e.g. nausea and abdominal pain). In conclusion, Serenoa repens is well tolerated and has greater efficacy than placebo and similar efficacy to finasteride in improving symptoms in men with BPH. Although there is a need for further comparative studies, particularly with alpha 2-receptor antagonists, available data indicate that Serenoa repens is a useful alternative to alpha 1-receptor antagonists and finasteride in the treatment of men with BPH.
The study carried out on rats given orally the n-hexane lipido/sterolic extract of Serenoa repens (LSESR), supplemented with [14C]-labelled oleic or lauric acids or beta-sitosterol, demonstrated that radioactivity uptake in prostatic tissues shows the highest level in the case of administration of LSESR supplemented with [14C]-labelled oleic acid. This was clearly demonstrated on a rat with an induced fibro-muscular hyperplasia of the prostate and by quantitative measurements of radioactivity. Ratios of radioactivity in tissues compared to plasma show an uptake of radioactivity greater in prostate as compared to other genital organs, i.e. the seminal vesicles or to other organs such as liver.
Testosterone treatment of rats produces prostatic hypertrophy and detrusor overactivity. Whether or not the detrusor overactivity can be related to an increase in the responsiveness of lower urinary tract smooth muscles is not known.
Male Sprague-Dawley rats were given daily injections of testosterone propionate for 2 weeks. Effects on cystometric parameters and on the responsiveness of isolated detrusor, urethral, and prostate smooth muscle preparations to drugs and electrical field stimulation were investigated.
Testosterone treatment increased prostatic weight twofold (controls, 768 mg; testosterone-treated, 1,478 mg), but not bladder weight (103 mg vs. 116 mg). Micturition pressure (77%), bladder capacity (75%), residual volume (56%), and micturition volume (83%) increased significantly in treated animals, and bladder overactivity developed. No effect of intraarterial doxazosin on these changes was observed. The differences in urodynamic parameters between control and testosterone-treated rats could not be correlated with changes in bladder, urethral, or prostate excitatory innervation, as revealed by responses to electrical field stimulation, or by smooth muscle responses to different contractant drugs.
Some of the urodynamic effects seen after testosterone treatment seem to be caused by the mechanical obstruction of the enlarged prostate. Since there were no changes in smooth muscle responsiveness, it is suggested that the bladder overactivity observed can partly be related to testosterone-induced changes of the micturition reflex at the lower urinary tract, spinal, and/or supraspinal levels.
In order to assess the efficacy of phytotherapeutic agents for the treatment of benign prostatic hyperplasia (BPH), a review of recently published double-blind placebo-controlled trials was undertaken.
Only those studies reviewed by the Other Medical Therapies Committee of the Fourth International Consultation on BPH were included.
These studies suggest a possible benefit for the use of phytotherapeutic preparations in the treatment of BPH.
These studies need to be confirmed in larger long-term placebo-controlled studies in order to ascertain the true efficacy of these agents.
This systematic review aimed to assess the effects of Serenoa repens in the treatment of Benign Prostatic Hyperplasia (BPH).
Trials were searched in computerized general and specialized databases (MEDLINE, EMBASE, Cochrane Library, Phytodok), by checking bibliographies, and by contacting manufacturers and researchers.
Trials were eligible if they (1) randomized men with BPH to receive preparations of Serenoa repens (alone or in combination) in comparison with placebo or other BPH medications, and (2) included clinical outcomes such as urologic symptom scales, symptoms, or urodynamic measurements. Eligibility was assessed by at least two independent observers.
Information on patients, interventions, and outcomes was extracted by at least two independent reviewers using a standard form. The main outcome measure for comparing the effectiveness of Serenoa repens with placebo or other BPH medications was the change in urologic symptom scale scores. Secondary outcomes included changes in nocturia and urodynamic measures. The main outcome measure for side effects was the number of men reporting side effects.
2939 men from18 randomized trials lasting 4 to 48 weeks were assessed. 16 trials were double-blinded and treatment allocation concealment was adequate in 9 studies. Compared with placebo, Serenoa repens improved urinary symptom scores, symptoms, and urinary flow measures. The weighted mean difference (WMD) for the urinary symptom score was -1.41 points (scale range 0-19), (95%CI = -2.52, -0.30, n = 1 study) and the risk ratio (RR) for self rated improvement was 1.75 (95%CI = 1.21, 2.54, n = 6 studies). The WMD for nocturia was -0.76 times per evening (95%CI = -1.22, -0.32; n = 10 studies). The WMD for peak urine flow was 1.93 ml/sec (95%CI = 0.72, 3.14, n = 8 studies). Compared with finasteride, Serenoa repens produced similar improvements in urinary symptom scores (WMD = 0.37 IPSS points (scale range 0-35), 95%CI = -0.45, 1.19, n = 2 studies) and peak urine flow (WMD = -0.74 ml/sec, 95%CI = -1.66, 0.18, n = 2 studies). Adverse effects due to Serenoa repens were mild and infrequent. Withdrawal rates in men assigned to placebo, Serenoa repens or finasteride were 7%, 9%, and 11%, respectively.
The evidence suggests that Serenoa repens improves urologic symptoms and flow measures compared with placebo. Serenoa repens produced similar improvement in urinary symptoms and flow compared to finasteride and is associated with fewer adverse treatment events. The long term effectiveness, safety and ability to prevent BPH complications are not known.
Objective:
To review the existing evidence regarding the efficacy and safety of medical therapy for lower urinary tract symptoms (LUTS) indicative of benign prostatic hyperplasia (BPH). To assess randomised controlled trials investigating the six alpha-adrenergic receptor antagonists (alpha-blockers), prazosin, alfuzosin, indoramin, terazosin, doxazosin, and tamsulosin, that benefit patients by relaxing prostatic smooth muscle, and the anti-androgen, finasteride, that mediates its more long-term benefits by reducing prostate size.
Results:
This review suggests that both classes of drug offer significant improvement in criteria used to evaluate symptomatic BPH and can be effective whilst being acceptably safe. Furthermore, the therapeutic efficacy of all contemporary alpha-blockers appear similar, both in terms of symptom relief and urodynamic improvements. Randomised controlled trials have additionally demonstrated that finasteride therapy can provide improvement in terms of quality of life indices, prostate volume, and risks of progressing to acute urinary retention or prostatic surgery. While alpha-blockers have a rapid onset of action, likely to produce a therapeutic result within weeks, regardless of whether prostatic enlargement or bladder outlet obstruction is present, finasteride appears to be effective for more long-term therapy for up to 4 years, but only in alleviating symptoms when they are associated with a significantly large prostate. Neither finasteride nor the alpha(1a)-receptor-selective blocker, tamsulosin, are associated with the lowering of blood pressure and incidence of cardiovascular side effects that are apparent with other less selective alpha-blocker therapies such as dizziness and postural hypertension. They are, however, both associated with an increased risk of sexual dysfunction, albeit less than those associated with surgical intervention. Whereas tamsulosin is associated only with ejaculatory dysfunction, finasteride is additionally linked to decreased libido and impotence.
Specialists of the urologic clinic of the I.M. Sechenov Moscow Medical Academy studied effectiveness of lipidosterol extract Serenoa repens (permixon) in 26 patients with prostatic hyperplasia (total prostate-specific antigen was under 4 ng/ml). The trial has been performed from November 1995 up to now. The drug was taken before meal with a small quantity of water in a total daily dose 320 mg twice a day. Initial IPSS values ranged from 8 to 18 scores (mean 11.65 +/- 0.59). Life quality index was 1 to 4 scores (mean 2.46 +/- 0.15). Initial size of the prostate varied from 26 to 63 cm3 (mean 36.23 +/- 1.57 cm3). Maximal urinary flow rate (Qmax) made up 8.7 to 14.6 ml/s (mean 11.83 +/- 0.31 ml/s). Residual urine was initially 0-60 ml (mean 10.58 +/- 2.91 ml). Permixon significantly reduced the disease symptoms and improved quality of life. 5 years of treatment decreased mean IPSS by 8.8 +/- 0.18 (75.5%). QOL--by 1.31 +/- 0.08 (53.3%), size of the prostate--by 10.81 +/- 0.55 cm3 (29.8%). Neither the symptoms nor quality of life became worse for these five years. The size of the prostate reduced in 16, unchanged in 9 and increased only in 1 patient. Qmax was initially under 15 ml/s and rose after the treatment by 4.13 +/- 0.51 ml/s (35%), on the average. Qmax rose above 15 ml/s in 16 patients. Residual urine increased during the treatment in one patient only. Permixon intolerance was not observed. Thus, continuous 5-year therapy with lipidosterol extract Serenoa repens (permixon) proved highly effective and safe in 26 patients with initial or moderate symptoms of prostatic hyperplasia.
While the lipidosterolic extract (LSESr) of Serenoa repens--Permixon--has been shown to have an equivalent efficacy to finasteride in patients with benign prostatic hyperplasia (BPH), to date, there has been no valid comparison of phytotherapy with alpha-blockers. The aim of this study was to assess the equivalent efficacy of Permixon and tamsulosin.
Eight hundred and eleven men with symptomatic BPH (international prostdate symptom score, I-PSS > or = 10) were recruited in 11 European countries for a 12-month, double-blind randomized trial. After a 4-week run-in period, 704 patients were randomly assigned to either tamsulosin 0.4 mg per day (N = 354) or Permixon 320 mg per day (N = 350). I-PSS, QoL and maximum urinary flow rate (Qmax) were evaluated at baseline and periodically for 1 year. Prostate volume and serum prostate-specific antigen (PSA) were measured at selection and at endpoint. The endpoint analysis was performed on the per-protocol (PP) population of 542 patients (tamsulosin: N = 273; Permixon: N = 269).
At 12 months, I-PSS decreased by 4.4 in each group and no differences were observed in either irritative or obstructive symptom improvements. The increase in Qmax was similar in both treatment groups (1.8 ml/s Permixon, 1.9 ml/s tamsulosin). PSA remained stable while prostate volume decreased slightly in the Permixon-treated patients. The two compounds were well tolerated, however, ejaculation disorders occurred more frequently in the tamsulosin group.
This study demonstrated that Permiwon and tamsulosin are equivalent in the medical treatment of lower urinary tract symptoms in men with BPH, during and up to 12 months of therapy.
This article reviews the structure and function of the sympathetic nervous system controlling the myogenic tone of the bladder outlet. Therefore, the sympathetic nervous system is partially responsible for urinary outflow resistance. The alpha 1-adrenoceptor antagonists alfuzosin, doxazosin, tamsulosin, or terazosin are able to reduce bladder outflow resistance, which leads to significant relief of LUTS (20-65%) and improvement of urinary flow (1-4.3 ml/s) in patients with symptomatic BPH. Alpha 1-blocker treatment works irrespective of the severity of symptoms, degree of subvesical obstruction, or prostate size. A significant reduction of residual urine was observed only occasionally, but at least alfuzosin is able to reduce the incidence of acute urinary retention. This article presents the results of 39 randomized, placebo-controlled trials with 14,924 patients as well as trials with alpha 1-blockers and plant extracts or finasteride. The results of these trials indicate that all alpha 1-blockers are equally effective. However, tolerability of alfuzosin or tamsulosin is superior to doxazosin or terazosin. Furthermore, treatment of hypertension with doxazosin or terazosin is no longer recommended due to the increased frequency of cardiovascular side effects seen in the ALLHAT Study. As alpha 1-blockers can relieve symptoms and improve urinary flow more effectively than plant extracts or finasteride, alpha 1-blockers are the treatment of first choice in patients with symptomatic BPH without or with a minor degree of subvesical obstruction.
The genesis of benign prostate hyperplasia (BPH) depends on two factors: testicular androgen and the aging process. The most important androgen in the prostate is dihydrotestosterone (DHT). In the aging male the level of DHT in the prostate remains largely constant although the plasma level of testosterone decreases. DHT is formed by the reduction of testosterone by the enzyme 5-alpha-reductase, which has two isoenzymes. The 5-alpha-reductase type 2 is the predominant isoenzyme in genital tissue and thus also in the prostate. Finasteride is a 5-alpha-reductase inhibitor, which is applied in the treatment of BHP and male baldness. In the doses used finasteride acts mainly by inhibiting the 5-alpha-reductase type 2, thereby reducing the serum level of DHT by approximately 70% and by about 85-90% in the prostate. Indeed the effect of finasteride in BPH was proven in clinical studies. However, the circulating and intraprostatic DHT could be further reduced by a more effective dual 5-alpha-reductase inhibitor, which would be efficacious in the treatment of benign prostate hyperplasia and other DHT-related disorders.
In different cell systems, the lipido-sterolic extract of Serenoa repens (LSESr, Permixon inhibits both type 1 and type 2 5alpha-reductase activity (5alphaR1 and 5alphaR2). LSESr is mainly constituted of fatty acids (90+/-5%) essentially as free fatty acids (80%). Among these free fatty acids, the main components are oleic and lauric acids which represent 65% and linoleic and myristic acids 15%. To evaluate the inhibitory effect of the different components of LSESr on 5alphaR1 or 5alphaR2 activity, the corresponding type 1 and type 2 human genes have been cloned and expressed in the baculovirus-directed insect cell expression system Sf9. The cells were incubated at pH 5.5 (5alphaR2) and pH 7.4 (5alphaR1) with 1 or 3nM testosterone in presence or absence of various concentrations of LSESr or of its different components. Dihydrotestosterone formation was measured with an automatic system combining HPLC and an on-line radiodetector. The inhibition of 5alphaR1 and 5alphaR2 activity was only observed with free fatty acids: esterified fatty acids, alcohols as well as sterols assayed were inactive. A specificity of the fatty acids in 5alphaR1 or 5alphaR2 inhibition has been found. Long unsaturated chains (oleic and linolenic) were active (IC(50)=4+/-2 and 13+/-3 microg/ml, respectively) on 5alphaR1 but to a much lesser extent (IC(50)>100 and 35+/-21 microg/ml, respectively) on 5alphaR2. Palmitic and stearic acids were inactive on the two isoforms. Lauric acid was active on 5alphaR1 (IC(50)=17+/-3 microg/ml) and 5alphaR2 (IC(50)=19+/-9 microg/ml). The inhibitory activity of myristic acid was evaluated on 5alphaR2 only and found active on this isoform (IC(50)=4+/-2 microg/ml). The dual inhibitory activity of LSESr on 5alpha-reductase type 1 and type 2 can be attributed to its high content in free fatty acids.
To evaluate the safety and efficacy of finasteride 5 mg during a 10-year period in men with enlarged prostates from a single center who participated in the double-blind and extension phases of the multicenter, Phase III, North American benign prostatic hyperplasia (BPH) trial. It is important that the long-term safety and efficacy of drugs intended for chronic administration in men with BPH be well understood.
The Phase III North American BPH trial involved a 1-year, placebo-controlled, double-blind study, followed by a 5-year open extension with finasteride 5 mg/day. The trial enrolled men with symptomatic BPH, an enlarged prostate on digital rectal examination, and no evidence of prostate cancer. Of the 46 patients originally enrolled from our institution, 43 were randomized to receive finasteride or placebo, of whom 41 (95%) completed the double-blind study and entered the 5-year extension. Thirty (73%) of these 41 patients completed the 5-year extension. Patients continued to be followed up by their physicians for an additional 5 years, for a total follow-up of at least 10 years.
Twenty-four (56%) of the original 43 patients randomized to finasteride or placebo were judged as successfully treated during the 10-year finasteride follow-up (17 patients taking finasteride alone at 10 years and 7 patients who were taking finasteride alone when they discontinued during the 10-year follow-up for reasons not related to finasteride treatment). Altogether, 22 (51%) of the original 43 randomized patients continued finasteride treatment at 10 years (17 taking finasteride alone, 4 taking finasteride plus an alpha-blocker, and 1 taking finasteride for treatment of hematuria). Finasteride was well tolerated, with no new adverse experiences occurring with increasing duration of exposure to the drug.
This long-term follow-up study has demonstrated that appropriately selected patients with symptomatic BPH and enlarged prostates are likely to have a long-term response to taking finasteride 5 mg daily.
This article examines the role of the androgen dihydrotestosterone (DHT) in the healthy and diseased prostate and considers the implications of the data on DHT for therapeutic approaches to benign prostatic hyperplasia (BPH). Development and maintenance of the normal prostate, as well as development of BPH, depend on a functional androgen-signaling axis, components of which include: (1) testosterone synthesis in the testes and adrenal glands; (2) conversion of testosterone to DHT; (3) transport of DHT to target tissues; and (4) binding of DHT to the androgen receptor with consequent modulation of genes. DHT plays a beneficial role in the developing prostate but it can be detrimental in the adult prostate in that it causes pathologic prostate growth. The role of DHT in other adult tissues is uncertain. DHT has not been shown to perform beneficial functions unique from testosterone in the adult male, and it is believed that its fundamental effect is to amplify testosterone's weaker hormonal signal. Increased understanding of the cellular mechanisms by which the androgen-signaling axis functions has led to advances in treatment for prostate disease. In BPH, the 5alpha-reductase inhibitors--the only class of therapy to act at the pathophysiologic substrate of the disease--arrest the disease process, reduce prostate volume, improve symptoms, and reduce the risk of acute urinary retention and BPH-related surgery. The availability of dutasteride, the first dual (Type 1/Type 2) 5alpha-reductase inhibitor, offers the opportunity for rapid and consistent inhibition of DHT.
In both ageing men and women, there is an increasing incidence of lower urinary tract symptoms (LUTS) which are increasing. These infections have many possible causes, including smooth muscle dysfunction, neurological factors and benign prostatic hyperplasia. Up to 15% to 25% of men aged 50-65 years have LUTS of sufficient severity to interfere with their quality of life. Although benign prostatic hyperplasia is an important cause of these symptoms, and can have serious consequences, clinicians should be aware of these other causes so that the appropriate diagnosis is made before invasive treatments are started. New medical treatments, including alpha-adrenergic blocking agents and 5 alpha-reductase inhibitors mean that many men without complications such as infection, bleeding, or chronic retention, and with mild to moderate symptoms, should be managed in primary care. Combined local protocols between primary and secondary care will help to establish which men with persistent symptoms or complications need referral for a urological opinion to determine the need for further investigation and more invasive forms of management. We review the pathophysiology of the disease, and current approaches to investigation and management of this common problem.
To compare the effect of a Serenoa repens extract with placebo for symptoms of benign prostatic hyperplasia (BPH).
In a double-blind placebo-controlled randomized trial between January 1999 and March 2000, 100 men with symptoms of BPH, aged < 80 years, with a maximum urinary flow rate of 5-15 mL/s for a voiding volume of 150 mL, were randomly and equally allocated to 320 mg S. repens extract or placebo (paraffin oil). The main outcome measures were the International Prostate Symptom Score (IPSS), peak urinary flow rate, and the Rosen International Index of Erectile Function (IIEF) questionnaire.
There was no significant difference between the treatments over the 12 weeks of the study in the IPSS, peak urinary flow rate or for the IIEF questionnaire.
During the trial all participants had some improvement in their symptoms of BPH but there was no significant beneficial effect of this S. repens extract over placebo in this 12-week trial.
For a better understanding of the hyperlipidemic function of saturated fat, we have studied the effects of diet supplementation with 10-20% coconut oil on the chick plasma and lipoprotein composition under postprandial and starvation conditions. A significant hypercholesterolemia was found in chicks fed the standard diet after 12 h of food deprivation. In these conditions, LDL-cholesterol also increased, whereas triglyceride levels were reduced in HDL, VLDL and chylomicron fractions. Coconut oil induced a significant hypercholesterolemia under both conditions, also increasing the plasma triglyceride content under postprandial conditions, but not after starvation. Coconut oil feeding increased all the chemical components of HDL, especially under postprandial conditions, but did not affect the HDL-triglycerides under food-deprivation conditions. Total cholesterol and triglyceride levels in LDL increased after coconut oil supplementation to the diet. Differences were more pronounced under postprandial conditions. Changes in VLDL and chylomicron composition were less evident.
In this article we aim to outline the recent advances in the evaluation of a patient with symptoms suggestive of benign prostatic hyperplasia. We define the role of the clinical evaluation and techniques that are evolving for the appropriate management of a patient with benign prostatic hyperplasia. Both non-invasive and invasive investigation techniques are reviewed.
Initiating early and appropriate treatment is the primary aim of investigation for a patient with lower urinary tract symptoms. Both clinical history and examination and appropriate investigations are vital to establishing a diagnosis. Symptom scores, prostate specific antigen and prostate volume were found to closely relate in predicting the progression of benign p