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A randomized double-blind placebo-controlled clinical trial of a product containing pumpkin seed extract and soy germ extract to improve overactive bladder-related voiding dysfunction and quality of life
Abstract
Overactive bladder (OAB) has become an increasing field of interest. Traditional use indicates that pumpkin seed (Cucurbita pepo L.) may be helpful in combating its symptoms. Additionally, soy isoflavones (Glycine max) are well-documented for hormonal imbalance related indications. The present randomized, double-blind, placebo-controlled study evaluated efficacy and safety of Cucuflavone (containing extracts of pumpkin seed and soy germ) in 120 subjects suffering from OAB. After 12 weeks, subjects taking Cucuflavone experienced a significant reduction versus baseline, in (1) urination frequency, (2) urgency, (3) incontinence frequency, maximum urgency score, (5) nocturnal urination frequency and (6) OAB-symptom scale. The placebo group reached significant differences for (1), (3) and (6). No adverse events or abnormal changes in safety parameters occurred. Thus, the combination of pumpkin seed and soy germ extract can be used as natural alternative to relieve symptoms of OAB and to improve quality of life.
... Cucurbita pepo L. [116] Cucurbita maxima Duchesne [117] Mahmoodpoor et al. [106] in a recent study performed on patients with severe diabetes from the Intensive Care Unit showed the hypoglycemic effect of C. maxima pulp. The subjects received five grams of C. maxima powder per 12 h for three consecutive days. ...
... Overactive bladder syndrome (OAB) is characterized by the frequent urge to urinate during the day and night, followed by an involuntary loss of urine [116]. A human clinical trial conducted by Shim et al. (2014) investigated the efficacy and utility of Cucuflavone (tablets with a mixture of plant extracts 87.5% C. pepo seeds and 12.5% soy) in reducing OAB symptoms [116]. ...
... Overactive bladder syndrome (OAB) is characterized by the frequent urge to urinate during the day and night, followed by an involuntary loss of urine [116]. A human clinical trial conducted by Shim et al. (2014) investigated the efficacy and utility of Cucuflavone (tablets with a mixture of plant extracts 87.5% C. pepo seeds and 12.5% soy) in reducing OAB symptoms [116]. The active compounds of Cucuflavone are phenols (pyrogallol) and isoflavones (genistein, daidzin). ...
Cucurbita genus has received a renowned interest in the last years. This plant species, native to the Americas, has served worldwide folk medicine for treating gastrointestinal diseases and intestinal parasites, among other clinical conditions. These pharmacological effects have been increasingly correlated with their nutritional and phytochemical composition. Among those chemical constituents, carotenoids, tocopherols, phenols, terpenoids, saponins, sterols, fatty acids, and functional carbohydrates and polysaccharides are those occurring in higher abundance. However, more recently, a huge interest in a class of triterpenoids, cucurbitacins, has been stated, given its renowned biological attributes. In this sense, the present review aims to provide a detailed overview to the folk medicinal uses of Cucurbita plants, and even an in-depth insight on the latest advances with regards to its antimicrobial, antioxidant and anticancer effects. A special emphasis was also given to its clinical effectiveness in humans, specifically in blood glucose levels control in diabetic patients and pharmacotherapeutic effects in low urinary tract diseases.
... The fibrous root of Gymnadenia orchidis was collected from the local market in Darjeeling, West Bengal, and India. The root Salep was prepared by suspending the powder root in double distilled water and used at an effective dose (200 mg/kg body weight) to the diabetic animals through oral supplementation Soy germ extract-pumpkin seed extract Shim et al., (2014) [9], South Korea 120 women aged between 35 and 70 years, suffering from urinary urgency, frequent urination, and nocturia, with or without incontinence for more than 3 months ...
... The fibrous root of Gymnadenia orchidis was collected from the local market in Darjeeling, West Bengal, and India. The root Salep was prepared by suspending the powder root in double distilled water and used at an effective dose (200 mg/kg body weight) to the diabetic animals through oral supplementation Soy germ extract-pumpkin seed extract Shim et al., (2014) [9], South Korea 120 women aged between 35 and 70 years, suffering from urinary urgency, frequent urination, and nocturia, with or without incontinence for more than 3 months ...
Background: In overcoming the problem of diabetes, developed countries have used herbal plants as an alternative treatment, considering that various types of synthetic drugs and available insulin therapy have physiological consequences in their use, such as insulin resistance, anorexia nervosa, brain atrophy, and fatty liver. Objective: This article aims to identify pumpkin seed interventions in controlling diabetes mellitus Methods: The article review was conducted using three bibliographic databases. Articles were selected based on 2011-2021 publications using the PRISMA flowchart of 2015 Results: A total of 1405 were obtained from three databases. About 17 articles according to the inclusion criteria and 7 articles were selected in this literature review. Based on the literature review results, it was found that previous researchers combined pumpkin seed with other plants to assess its efficacy in controlling blood glucose. Pumpkin seed had been tested on many experimental animals such as mice, rats, and rabbits. It showed hypoglycemic activity. Conclusion: Pumpkin seed is an herbal plant that has advantages in preventing and maintaining health as well as being used as a complementary therapy for people with diabetes mellitus
... They are also used as food additives in the baking industry [ 6 , 14 ]. A significant number of studies have established a relationship between natural bioactive components of foods and health promotion and disease prevention [15][16][17] . The foods that qualify this diet-health relationship are known as functional foods [13] . ...
... With the global production of 27 million metric tons annually [50] , pumpkin is one of the well-studied diseasepreventing vegetables [15][16][17][18][19]. Currently, the interest of public and health professionals towards the importance of functional foods in the prevention of diseases is gaining its grounds [ 16 , 37 , 39 , 40 , 51-53 ]. ...
Pumpkin seeds may be tiny, but they are densely packed with useful nutrients and nutraceuticals such as amino acids, phytosterols, unsaturated fatty acids, phenolic compounds, tocopherols, cucurbitacins, and valuable minerals. All these bioactive compounds are important to a healthy life and well-being. The purpose of this review is to merge the evidence-based information on the potential use of pumpkin seeds as a functional food ingredient and associated biological mechanisms, collected from electronic databases (Sci-enceDirect, ResearchGate, PubMed, Scopus and Google Scholar) up to January 2020. Bioactive compounds in pumpkin seeds exhibit promising activities such as anthelmintic, antidiabetic, antidepressant, antioxidant, antitumor, and cytoprotective. Furthermore, these bioactives carry potential in ameliorating microbiological infections, hepatic, and prostate disorders. As evidenced from literature, pumpkin seeds show potential to be used as both a traditional and functional food ingredient provided further animal and clinical investigations are carried out to establish the respective molecular mechanisms and safety profile.
... It decreased the frequency of urination during both the night and daytime, and frequency of incontinence also improved in patients (Sogabe & Terado, 2001). In another study, cucuflavone (the combination of pumpkin seed and soy germ extract) can be used as natural alternative to relieve symptoms of over active bladder and to improve quality of life (Shim et al., 2014). There is significant reduction in urination frequency, urgency, incontinence frequency, maximum urgency score, nocturnal urination frequency and over active bladder symptom scale. ...
Cucurbit plants were used actively as traditional herbal remedies for various diseases. The medicinal importance of plants lies in some chemical substances or secondary metabolites that produce a specific physiological action on the human body. Secondary metabolites are non nutritive chemical constituents of plants which are restricted in distribution in the particular plant species. The scarcity of scientific reports of vegetable gourds compared to the traditional usage and folkloric beliefs has further limited us in proper inclusion of cucurbits in our diet and versatile utility. The versatile utility of gourd vegetables as folk medicine and functional food ingredient provoked a compilation of a comprehensive review of these vegetables about their traditional usage and nutritional and medicinal properties together with their phytochemicals. Understanding the nutritional potential of gourd vegetables from scientific reports may influence both the work areas and consumers in the appropriate direction. In this sense, the present chapter aims to provide compilation of references and a detailed overview to the folk medicinal uses of Cucurbita plants. Brief discussion of phytochemicals and its activities are given in the text and for further details, cited references in the text and tables can be consulted.
... Urox produced more extensive benefits for symptoms of OAB and UI than has been shown with earlier herbal research, and within a shorter timeframe. A 12-week randomised trial with women using a pumpkin seed extract (Cucurbita pepo.) and a proprietary soy germ extract (Glycine max) combination showed no significance in reducing incontinence [48]. Whilst frequency, urgency and nocturia improved, the magnitude of effect was consistently less and time frame for results, longer than with Urox. ...
Diagnosis, lower urinary tract symptoms including overactive bladder and urinary incontinence, causes and contributing factors, LUTS questionnaires, differential diagnosis, therapeutic considerations, including pharmaceutical, physical therapy, behavior therapy, botanical medicines, dietary supplements and nutrition modifications, medications that increase urgency, lifestyle factors, and various holistic treatments.
... Shim et al. investigated the efficacy and utility of Cucuflavone (tablets with a mixture of plant extracts 87.5 % Cucurbita pepo seeds and 12.5 % soy) in reducing OAB symptoms [24]. The final results of the investigation showed that urinary incontinence, the frequency of daily and nocturnal urination was statistically significantly reduced compared to the initial parameters. ...
Introduction
The prevalence of overactive bladder (OAB) in women increases with age and is present in approximately 30% of women over the age of 65 years. A high percentage of patients undergoing pharmacological therapy discontinue treatment for side effects and costs. Using an oral supplement (Kubiker®), consisting of vitamins, cucurbita maxima, capsicum annum, polygonum cuspidatum and L-Glutammin, for the control of urinary symptoms, could be a valid alternative.
Objective
To assess the efficacy and tolerability of this oral supplement in women affected by OAB.
Methods
We performed a retrospective, longitudinal, observational, cohort study of 84 patients affected by OAB, who received a prescription of Kubiker® for 12 weeks (2 tablets a day for the first month, then 1 tablet a day for 2 months). Primary outcome was to check the efficacy of therapy through questionnaire Patient global impression of improvement (PGI-I) after 12 weeks of therapy. The secondary outcome was to evaluate the difference in the answers of the Overactive Bladder Questionnaire (OAB-Q) before and after therapy. Adherence to therapy was also evaluated.
Results
Data showed a positive effect of Kubiker® in the control of urinary symptoms after 12 weeks of therapy. Paired T-Test used for the evaluation of OBS before and after the treatment showed a p-value < 0.001. The analysis of this questionnaire especially showed an improvement in the responses concerning the symptoms of urination urgency and urge incontinence.
Conclusion
Therapy with oral supplement based on vitamins (C and D), cucurbita maxima, capsicum annum, polygonum cuspidatum and L-Glutammin is an effective and well-tolerated treatment for overactive bladder.
... Furthermore, oral administration of pumpkin seed oils was effective against cytotoxic and gynotoxic effects of azathioprine in mice by decreasing DNA fragmentation, reducing the frequencies of micronucleated polychromatic erythrocytes (Mn-PCEs) and sperm abnormalities and increasing total sperm count, the percentage of PCEs and the ratio of PCEs to normochromatic erythrocytes (NCEs) [367]. Oral administration of C. maxima seed oil may reduce urinary disorders [368], while a mixture of soy and pumpkin seeds reduces urination and inconsistence frequency [369]. Moreover, consumption of capsules with pumpkin seed oil (PSO) at doses of 400 mg/d -1 increased hair count by 40% in patients with androgenetic alopecia, probably due to blocking of 5-α-reductase [370], while pumpkin seed supplementation reduced calcium-oxalate crystal occurrence and calcium level and increased phosphorus levels, thus highlighting its potential use against bladder stone disease [371]. ...
... Furthermore, oral administration of pumpkin seed oils was effective against cytotoxic and gynotoxic effects of azathioprine in mice by decreasing DNA fragmentation, reducing the frequencies of micronucleated polychromatic erythrocytes (Mn-PCEs) and sperm abnormalities and increasing total sperm count, the percentage of PCEs and the ratio of PCEs to normochromatic erythrocytes (NCEs) [367]. Oral administration of C. maxima seed oil may reduce urinary disorders [368], while a mixture of soy and pumpkin seeds reduces urination and inconsistence frequency [369]. Moreover, consumption of capsules with pumpkin seed oil (PSO) at doses of 400 mg/d -1 increased hair count by 40% in patients with androgenetic alopecia, probably due to blocking of 5-α-reductase [370], while pumpkin seed supplementation reduced calcium-oxalate crystal occurrence and calcium level and increased phosphorus levels, thus highlighting its potential use against bladder stone disease [371]. ...
Cucurbitaceae represents a large plant family with more than 120 genera and 800 species, among which many significant cultivated vegetables species are included, such as watermelon, melon, cucumber and cucurbits (squash, pumpkin and zucchini). These species are usually consumed for its edible fruit, however several other uses have been reported for the various plant parts, including medicinal and therapeutic ones among others. The present chapter will demonstrate the most common vegetable species in terms of their chemical composition and health effects, as well as their edible, medicinal and industrial uses, based on the phytochemical content of the various plant parts. Special focus will be given on cucurbitacins which are an important group of phytochemicals present in the Cucurbitaceae family, since several studies have confirmed its bioactive properties and multiple health effects. Finally, selected less known species of this family (gourds) will be presented, considering their important health effects and their use in vegetable grafting. In conclusion, future perspectives for further valorization of these species will be highlighted, especially for the ones that are less commonly used.
... Urox produced more extensive benefits for symptoms of OAB and UI than has been shown with earlier herbal research, and within a shorter timeframe. A 12-week randomised trial with women using a pumpkin seed extract (Cucurbita pepo.) and a proprietary soy germ extract (Glycine max) combination showed no significance in reducing incontinence [48]. Whilst frequency, urgency and nocturia improved, the magnitude of effect was consistently less and time frame for results, longer than with Urox. ...
Abstract Background Storage lower urinary tract symptoms (LUTS) including overactive bladder (OAB) and urinary incontinence (UI) affect millions of people worldwide, significantly impacting quality of life. Plant based medicines have been documented both empirically and in emerging scientific research to have varying benefits in reducing bladder symptoms. We assessed the efficacy of Urox®, a proprietary combination of phytomedicine extracts including, Cratevox™ (Crataeva nurvala) stem bark, Equisetem arvense stem and Lindera aggregata root, in reducing symptoms of OAB and UI. Methods Efficacy of the herbal combination on a variety of bladder symptoms compared to an identical placebo, were documented in a randomised, double-blind, placebo controlled trial conducted at two primary care centres. Data were collected at baseline, 2, 4 and 8 weeks, with the primary outcome being self-reported urinary frequency. Statistical analysis included mixed effects ordered logistic regression with post hoc Holm’s test to account for repeated measures, and included an intention-to-treat analysis. Results One hundred and fifty participants (59% female, aged; mean ± SD; 63.5 ± 13.1 years) took part in the study. At week 8, urinary day frequency was significantly lower (OR 0.01; 95%CI 0.01 to 0.02; p
... Which may explain why it has been used in folk medicine to treat kidney, bladder and prostate disorders [27] Pumpkin seed oil has also been shown to improve symptoms of overactive bladder [28]. Pumpkin seed extract in combination with soybean extracts have been shown to have promising potential treat urinary tract complications including SUI, overactive bladder, frequency and nocturia [29][30][31][32]. This study differs in that it focused solely on urinary incontinence in perimenopausal women using a novel formula containing a soybean extract containing a high level of genistein in combination with a proprietary standardized pumpkin seed extract. ...
... maxima) seed oil extracts at a dosage of 10 g of oil/day for 6-12 weeks reduced the bladder over-activity in patients [54]. The combination of pumpkin seed and soy (Glycine max) germ extract, when administered for 12 weeks led to reduction in urination, and incontinence frequency [55]. Bladder stone formation is debilitating. ...
Cucurbitaceae family members such as pumpkin and watermelon have seeds that are discarded as the by-products of food processing. However, they have been discovered to contain a rich repertoire of nutrients such as proteins, unsaturated fatty acids, phenolic acids, carotenoids, tocopherol, phytosterol, squalene etc. Biological assays have proven the seed extracts to exert antioxidative, hypoglycemic, anticancer, antihypertensive, cardioprotective, antilipemic, gynoprotective, and anthelmintic properties. Further, the seeds do not contain any major anti-nutrients. Phytoestrogens like β-sitosterol occur, which might be acting as agonists or antagonists of estrogen and testosterone, given their validated role in gyenic and prostate health. Few instances of intestinal bezoar, and allergy, following pumpkin seeds consumption have emerged. After the risk-benefit analysis though exhaustive literature search, it can be suggested that these seeds are underutilized and they can be used to formulate a myriad of nutraceuticals.
... This strong placebo effect in combination with short study duration was also observed in a recently published study that investigated the effects of a nutraceutical ingredient on overactive bladderrelated voiding dysfunction and quality of life. 15 Despite the strong placebo effects observed after 4 and 8 weeks, these effects returned to baseline after 12 weeks. This allowed the researchers to observe statistically significant effects for the treatment group after 12 weeks, implying that the length of the study was of importance. ...
ABSTRACT This exploratory study was designed to assess the effectiveness of a lignan-rich extract of flaxseed hulls (LinumLife EXTRA(®)) in alleviating symptoms in subjects with benign prostatic hyperplasia (BPH) compared with placebo. Two dosages of extract were compared against placebo in a double-blinded, randomized, parallel, multicenter study. Newly diagnosed cases of BPH in patients aged 45-75 years with an American Urological Association Symptom Index (AUASI) score of ≥13 were included. Study treatment consisted of 500 or 1000 mg of extract containing 100 mg (low-dose active [LDA] group, n=26) or 200 mg (high-dose active [HDA] group, n=26) of secoisolariciresinol diglucoside (SDG), respectively. The placebo (P) group (n=28) received matching maltodextrin capsules. Sixty subjects (LDA [n=19], HDA [n=20], and P [n=21]) completed the study as per the protocol requirements. Change in the AUASI score within a period of 8 weeks, from baseline to end of treatment, was assessed. Significant improvement of obstructive symptoms and management of irritable BPH symptoms was achieved in all groups after treatment. Due to a strong placebo effect, there was no statistical difference between the groups that were treated with flaxseed hull extract as compared with the placebo group. Treatment with flaxseed hull extract did not lead to adverse effects compared with placebo. Supplementation with flaxseed hull extract was found to be safe and well-tolerated and may have improved the quality of life of individuals with BPH. The significant placebo effect as well as the number of subjects per treatment group and the relative short duration of the study may explain the lack of statistical significance between groups.
A pumpkin seed, also known as a “pepita”, means “little seed of squash”. Cucurbita pepo is the pumpkin species of the genus: Cucurbita, family: Cucurbits, sub-family: Cucurbitaceae, genera: Cucurbita L. Cucurbita pepo L. is the species among Cucurbitaceae family having the greatest monetary value of the genus. The seeds are typically rather flat, asymmetrically oval, light green in color, and may have a white outer hull. The Cucurbita pepo seeds have potential application and can be used as an alternative oil and protein source in novel food formulations such as cooking oils, as an ingredient in margarine blends, flours for instant soups, cookies, etc.
Aim
The present review aims to discuss therapeutic potential and pharmaceutical applications of the Cucurbita plant.
Methods
Various search engines such as science direct, scopus, google scholar, google patent etc. were used for the literature survey.
Discussion
During the literature survey, it was observed that different parts of the Cucurbita species have significant therapeutic effects against disease conditions. They have antimicrobial, antifungal, antiviral, antiulcer, antidiabetic, anticancer, anti-inflammatory etc. activity. Studies also showed that various pharmaceutical formulations have been prepared for the delivery of therapeutic active ingredients of cucurbits. A list of patents based on pharmaceutical formulations and therapeutic activity has been also included in the manuscript.
Conclusion
It can be concluded from the findings that Cucurbita has significant therapeutic potential, clinical effects and can be utilized for the treatment of various diseases.
Pumpkin seeds have been known in folk medicine as remedy for kidney, bladder and prostate disorders since centuries. Nevertheless, pumpkin research provides insufficient data to back up traditional beliefs of ethnomedical practice. The bioactivity of a hydro-ethanolic extract of pumpkin seeds from the Styrian pumpkin, Cucurbita pepo L. subsp. Pepo var. styriaca, was investigated. As pumpkin seed extracts are standardized to cucurbitin, this compound was also tested. Transactivational activity was evaluated for human androgen receptor, estrogen receptor and progesterone receptor with in vitro yeast assays. Cell viability tests with prostate cancer cells, breast cancer cells, colorectal adenocarcinoma cells and a hyperplastic cell line from benign prostate hyperplasia tissue were performed. As model for non-hyperplastic cells, effects on cell viability were tested with a human dermal fibroblast cell line (HDF-5). No transactivational activity was found for human androgen receptor, estrogen receptor and progesterone receptor, for both, extract and cucurbitin. A cell growth inhibition of ~ 40–50% was observed for all cell lines, with the exception of HDF-5, which showed with ~ 20% much lower cell growth inhibition. Given the receptor status of some cell lines, a steroid-hormone receptor independent growth inhibiting effect can be assumed. The cell growth inhibition for fast growing cells together with the cell growth inhibition of prostate-, breast- and colon cancer cells corroborates the ethnomedical use of pumpkin seeds for a treatment of benign prostate hyperplasia. Moreover, due to the lack of androgenic activity, pumpkin seed applications can be regarded as safe for the prostate.
Objectives. To prospectively examine the efficacy and safety of propiverine hydrochloride in patients with overactive bladder (OAB) symptoms who poorly responded to previous treatment with solifenacin, tolterodine or imidafenacin. Methods. Patients aged ≥20 with persisting OAB symptoms (≥6 in OAB symptom score (OABSS)) even after at least 4-week treatment using solifenacin, tolterodine or imidafenacin were enrolled. Propiverine 20 mg/day was administered for 12 weeks to 70 patients who desired the further improvement of OAB symptoms and 3 who had intolerable adverse events of previous drugs. The OABSS and postvoid residual urine volume (PVR) were determined before and at 4 and 12 weeks of treatment. Results. Of 73 patients enrolled (29 males and 44 females, median age 71 years), 52 completed the protocol treatment. The OABSS was significantly improved by propiverine treatment (9.0 at baseline, 6.2 at 4 weeks, 6.3 at 12 weeks (P < 0.001)). The scores of OAB symptoms (nighttime frequency, urgency and urge incontinence) except daytime frequency also improved significantly. No increase in PVR was observed. The most frequent adverse event was dry mouth (13.7%), followed by constipation (6.8%). Conclusions. Propiverine is useful to improve OAB for patients who poorly respond to solifenacin, tolterodine or imidafenacin.
To analyze age-associated changes as a motive for urodynamics and urodynamic diagnosis in community-dwelling menopausal women and to discuss the role of menopause and ageing.
Four hundred and forty nine consecutive menopausal women referred for urodynamic evaluation of lower urinary tract (LUT) symptoms, met the inclusion criteria and were stratified into 3 age groups: 55-64 years (A), 65-74 years (B), and 75-93 years (C). Comprehensive assessment included previous medical history and clinical examination. Studied items were motive for urodynamics, results of uroflows (free flow and intubated flow) and cystometry, urethral pressure profilometry, and final urodynamic diagnosis.
The main motive was incontinence (66.3%) with significant increase of mixed incontinence in group C (p = 0.028). Detrusor function significantly deteriorated in the oldest group, mainly in absence of neurological disease (overactivity p = 0.019; impaired contractility p = 0.028). In the entire population, underactivity predominated in group C (p = 0.0024). A progressive decrease of maximum urethral closure pressure occurred with ageing. In subjects with no detrusor overactivity there was a decrease with age of detrusor pressure at opening and at maximum flow, and of maximum flow while post void residual increased only in the C group.
In our population of community-dwelling menopausal women, incontinence was the main motive for urodynamics increasing with ageing. A brisk change in LUT function of women older than 75 years underlined deterioration in bladder function with a high incidence of detrusor hyperactivity with or without impaired contractility while change in urethral function was progressive. Effect of ageing appears to be predominant compared to menopause.
Interest in the physiologic and pharmacologic role of bioactive compounds present in plants has increased dramatically over the last decade. Of particular interest in relation to human health are the classes of compounds known as the phytoestrogens, which embody several groups of non-steroidal estrogens, including isoflavones and lignans that are widely distributed within nature. The impact of dietary phytoestrogens on normal biologic processes was first recognized in sheep. Observations of sheep grazing on fields rich in clover and cheetahs fed high soy diets in zoos suggested that flavonoids and related phytochemicals can affect mammalian health. Endogenous estrogens have an important role not only in the hypothalamic-pituitary-gonadal axis, but also in various non-gonadal systems, such as cardiovascular systems, bone, and central nervous systems, and lipid metabolism. There have been several clinical studies of hormone replacement therapy (HRT) in post-menopausal women to examine whether HRT has beneficial effects on the cardiovascular system, bone fractures, lipid metabolism, and Alzheimer's disease. In addition, estrogen contributes to the development of some estrogen-dependent cancers, such as breast cancer and prostate cancer and the number of patients with these cancers is increasing in developed countries. Although recent mega-studies showed negative results for classical HRT in the prevention of some of these diseases, the molecules that interact with estrogen receptors are candidate drugs for various diseases, including hormone-dependent cancers. This review focuses on the molecular properties and pharmaceutical potential of phytoestrogens.
Animal studies have shown that soy isoflavones have an effect in preventing estrogen-related bone loss, but few data are available in humans, especially in the Asian populations. This double-blind, placebo-controlled, randomized trial examines the effects of soy isoflavones on bone loss in postmenopausal Chinese women, aged 48-62 yr. Two hundred and three eligible subjects were randomly assigned to three treatment groups with daily doses of placebo (1 g starch; n = 67), mid-dose (0.5 g starch, 0.5 g soy extracts, and approximately 40 mg isoflavones; n = 68), and high dose (1.0 g soy extracts and approximately 80 mg isoflavones; n = 68). All were given 12.5 mmol (500 mg) calcium and 125 IU vitamin D(3). Bone mineral density (BMD) and bone mineral content (BMC) of the whole body, spine, and hip were measured using dual energy x-ray absorptiometry at baseline and 1 yr post treatment. Both univariate and multivariate analyses showed that women in the high dose group had mild, but statistically significantly, higher favorable change rate in BMC at the total hip and trochanter (P < 0.05) compared with the placebo and mid-dose groups, even after further adjustments for the potential confounding factors. Further stratified analyses revealed that the positive effects of soy isoflavone supplementation were observed only among women with lower initial baseline BMC (median or less). In conclusion, soy isoflavones have a mild, but significant, independent effect on the maintenance of hip BMC in postmenopausal women with low initial bone mass.
Estrogen therapy is, to date, the most effective treatment of menopausal syndrome and also has a favorable effect on lipid profiles. Because of its potential adverse effects, however, a more acceptable alternative therapy needs to be identified. This study examines the effect of soy germ isoflavones on menopausal symptoms and serum lipids.
Ninety early postmenopausal Chinese women, aged 45 to 60 years, were randomly assigned to three treatment groups (30 each) receiving daily doses of 0 (placebo), 84, and 126 mg of soy germ isoflavones. Hot flush frequency, Kupperman scores, serum 17β-estradiol, follicle-stimulating hormone, luteinizing hormone, and serum lipids, including triglyceride, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, apolipoprotein A-I, and apolipoprotein B100, were assessed at baseline and at 12 and 24 weeks after treatment.
Both the frequency of hot flushes and the Kupperman index score decreased in all three treatment groups during the intervention period, but the percentage decreases in both were significantly greater in the two isoflavone groups (44.3 ± 19.1 and 57.8 ± 37.4 [84 mg isoflavones]; 48.5 ± 27.2 and 56.7 ± 26.7 [126 mg isoflavones]) than in the placebo group (27.8 ± 15.5 and 34.6 ± 46.2; p < 0.01). There was no significant difference in the changes in estradiol, follicle-stimulating hormone, and luteinizing hormone among the three treatment groups during the study, and no significant differences were observed in the lipid components.
A daily supplement of 84 or 126 mg soy germ isoflavones may improve menopausal symptoms, although neither dose was found to affect lipid profiles in early postmenopausal Chinese women after 24 weeks of treatment. The favorable effects are unlikely to be associated with female hormones.
Conservative management, such as pelvic floor muscle training (PMFT), is commonly recommended as first-line therapy for women with stress urinary incontinence (SUI).
We randomly assigned 245 women with SUI to 12 weeks of circular muscle exercises (Paula method) or PMFT in order to assess whether these approaches are equivalent. End points after 12 weeks included urinary leak as measured by a 1-hour pad test, subjective assessment of incontinence, and quality of life (QOL). Cure was defined as urinary leakage of <1 g.
The mean decrease in urinary leakage was 7.9 g (SD 12.1) among women in the Paula group and 8.9 g (SD 18.2) in the PFMT group (90% confidence interval [CI] of between-group difference was -4.68 g to 3.0 g). This did not meet the prespecified criterion for equivalence. There were 15.2% (p = 0.04) more cures in those randomized to the Paula method. Improvement in subjective urinary complaints and QOL was observed in both groups. The study was limited by a dropout rate of 26.6%.
Both methods are efficacious in women with SUI. The results suggest superiority of the Paula method in terms of cure rate.
To estimate the relationship between changes in estradiol (E2) levels over time and lower urinary tract symptoms in premenopausal women as they transition to menopause.
A self-administered validated questionnaire to measure lower urinary tract symptoms was administered to 300 women at the 11th assessment period on an ongoing longitudinal Penn Ovarian Aging cohort study. The association between the change in E2 over time through the menopausal transition and lower urinary tract symptoms (urinary incontinence, filling symptoms, voiding dysfunction) was determined. Risk factors associated with lower urinary tract symptoms were determined by univariable analysis and multivariable linear regression.
Estradiol levels and menopausal stage at one point in time were not associated with lower urinary tract symptoms. Women with a sharp decline in E2 levels over time had significantly lower urinary incontinence scores in comparison with women without a change in E2 levels through the study period (mean+/-standard deviation 3.11+/-2.86 compared with 2.08+/-2.43, adjusted mean difference -0.93, 95% confidence interval [CI] -1.8 to -0.02). Women between the ages of 45 years to 49 years had significantly higher urinary incontinence scores than women woman age older than 55 years (1.59+/-1.86 compared with 3.04+/-2.93, adjusted mean difference 1.0, 95% CI 0.01-2.1). Women with a body mass index greater than 35 also had significantly higher urinary incontinence scores than women in the normal weight range, (3.53+/-3.16 compared with 1.98+/-2.52, adjusted mean difference 1.5, 95% CI 0.59-2.3) after adjusting for changes of E2 through the menopausal transition. High anxiety was associated with worsening scores in all three lower urinary tract symptoms domains (incontinence, filling, voiding).
Women with a sharp decline in E2 through the menopausal transition have significantly lower urinary incontinence scores. Urinary filling symptoms and voiding dysfunction were not associated with changes in E2 through the menopausal transition.
II.
Tolterodine is a new, potent and competitive muscarinic receptor antagonist in clinical development for the treatment of urge incontinence and other symptoms of unstable bladder. Tolterodine has a high affinity and specificity for muscarinic receptors in vitro and it exhibits a selectivity for the urinary bladder over salivary glands in vivo. A major active metabolite, (PNU-200577) the 5-hydroxymethyl derivative of tolterodine, has a similar pharmacological profile. Based on pharmacological and pharmacokinetic data, it has been concluded that this metabolite contributes significantly to the therapeutic effect of tolterodine. The bladder selectivity demonstrated by tolterodine and PNU-200577 in vivo cannot be attributed to selectivity for a single muscarinic receptor subtype. Moreover, this favourable tissue-selectivity seems to occur also in humans. Tolterodine is well tolerated and it exerts a marked effect on bladder function in healthy volunteers. Phase II data indicate that tolterodine is an efficacious and safe treatment for patients with idiopathic detrusor instability or detrusor hyperreflexia. An optimal efficacy/side-effect profile is obtained with tolterodine, at a dosage of 1 or 2 mg twice daily, which seems to have less propensity to cause dry mouth than the currently available antimuscarinic drugs.
Broadly defined, phytoestrogens include isoflavones, coumestans, and lignans. A number of these compounds have been identified in fruits, vegetables, and whole grains commonly consumed by humans. Soybeans, clover and alfalfa sprouts, and oilseeds (such as flaxseed) are the most significant dietary sources of isoflavones, coumestans, and lignans, respectively. Studies in humans, animals, and cell culture systems suggest that dietary phytoestrogens play an important role in prevention of menopausal symptoms, osteoporosis, cancer, and heart disease. Proposed mechanisms include estrogenic and antiestrogenic effects, induction of cancer cell differentiation, inhibition of tyrosine kinase and DNA topoisomerase activities, suppression of angiogenesis, and antioxidant effects. Although there currently are no dietary recommendations for individual phytoestrogens, there may be great benefit in increased consumption of plant foods.
To offer a critical overview of the basis for the International Continence Society (ICS) classification of detrusor instability, to summarize current diagnostic methodologies, and to outline the etiologic factors that should be excluded in the diagnosis of idiopathic overactive bladder.
The current ICS definitions of overactive bladder are discussed. Issues related to the diagnosis of detrusor instability (DI) are addressed through a review of the literature.
The term idiopathic overactive bladder reflects the present lack of knowledge concerning vesicourethral function and dysfunction. The term is used to apply to a wide spectrum of different conditions that may have a common final pathophysiologic pathway. This heterogeneous group of conditions could be subdivided on the basis of presumptive etiopathogenesis, urodynamic patterns, and response to treatment. The diagnosis of DI, its rate of detection, and its urodynamic patterns depend on the type of urodynamic test used and the way the test is performed. The ICS definitions of DI have been called into question by the results of studies using urodynamic tests in addition to, or instead of, provocative cystometry--for instance, ambulatory urodynamics, urethrocystometry, the ice-water test, and evaluation of the voiding phase. The literature supports a broadening of the ICS criteria for excluding all known causes of DI when establishing the diagnosis of idiopathic overactive bladder.
Appropriate longitudinal studies, using contemporary urodynamic tests and knowledge, are needed to improve the identification of subsets of patients with overactive bladder who have different prognoses and outcomes. The ICS definitions and classification should be updated.
Phytoestrogens represent a family of plant compounds that have been shown to have both estrogenic and antiestrogenic properties. A variety of these plant compounds and their mammalian metabolic products have been identified in various human body fluids and fall under two main categories: isoflavones and lignans. A wide range of commonly consumed foods contain appreciable amounts of these different phytoestrogens. For example, soy and flax products are particularly good sources of isoflavones and lignans, respectively. Accumulating evidence from molecular and cellular biology experiments, animal studies, and, to a limited extent, human clinical trials suggests that phytoestrogens may potentially confer health benefits related to cardiovascular diseases, cancer, osteoporosis, and menopausal symptoms. These potential health benefits are consistent with the epidemiological evidence that rates of heart disease, various cancers, osteoporotic fractures, and menopausal symptoms are more favorable among populations that consume plant-based diets, particularly among cultures with diets that are traditionally high in soy products. The evidence reviewed here will facilitate the identification of what is known in this area, the gaps that exist, and the future research that holds the most potential and promise.
Overactive bladder (OAB) is a disorder that encompasses frequency, urgency, and urge incontinence, singly or in combination. It often has a significant individual impact on quality of life and on limitations to activities, yet most individuals with OAB do not seek medical care. Therefore, it is not possible to estimate the prevalence and, more generally, the societal impact of OAB based on medical encounter data. With few exceptions, most epidemiologic studies have focused on urge incontinence, the most severe form of OAB. The prevalence of OAB increases with age and is more common in women than men. However, prevalence estimates vary considerably among studies, ranging from 3% to 43%. The variation in estimates from epidemiologic studies is the result in part of differences in the criteria used to define a case of urge incontinence among studies. This problem is attributable in part to the lack of a standardized, validated, and operational definition. Nonetheless, consensus exists regarding the significant individual and societal impact of urge incontinence and the recognition that it is underdiagnosed and undertreated. Frequency and urgency, the other 2 symptoms of OAB, have not received the same level of attention as urge incontinence, yet the societal impact of these symptoms of OAB may be considerably greater. Overall, frequency and urgency are considerably more common symptoms than urge incontinence, especially between 35 and 55 years of age, the period of peak productivity for most workers. Recent evidence indicates that a substantial proportion of individuals with frequency and urgency report a diminished quality of life and interference with activities in a number of roles, including work. Efforts are under way to more accurately describe the prevalence of frequency and urgency, using a validated and standardized epidemiologic case definition to determine the individual impact of each symptom of OAB and to estimate societal costs.
To compare the efficacy and labour costs of nurse continence advisors and urogynaecologists in conservative management of urinary incontinence.
Single centre randomised controlled trial of patients with mild or moderate leakage.
Tertiary urogynaecology unit.
One hundred and forty-five consecutive patients with stress and/or urge incontinence.
Standardised conservative therapy regimens, provided by nurse continence advisors and urogynaecologists.
One-hour pad test, frequency volume charts, a 20-point incontinence score and two quality of life tests, staff treatment times and costs.
Of 110 women who completed 12-week treatments, 64% of the women in the nurse continence advisor group (n = 58) and 52% of women treated by urogynaecologists (n = 52) were asymptomatic (dry pad test; OR 1.63, 95% CI 0.71-3.75). There was no significant difference between clinician groups for change in pad test result (P = 0.71), voids/day (0.43), incontinence score (P = 0.57) or quality of life scores (urogenital distress inventory, P = 0.27; Incontinence Impact Questionnaire, P = 0.41). Despite the expected longer consultation times for the advisor group (median 160 min, interquartile range [IQR] 130-210) versus the urogynaecologist group (median 90 min, IQR 60-120), the per capita labour cost for advisor treatment (median AU$59.20, IQR 48.10-77.70) was lower than for treatment given by urogynaecologists (median cost AU$ 189.70, IQR 120.60-250.70, Mann-Whitney U test, P < 0.0001). At 2.5 years, 23/58 patients (40%) treated by advisor and 27/52 patients (52%) treated by urogynaecologist group, who had been cured and discharged, were available for contact. Of these, 29% of women in the nurse continence advisor group and 41% of those treated by urogynaecologists remained continent (on 20-point score). Quality of life improvement persisted equally in both groups. These data should be interpreted cautiously due to a 24% dropout rate.
The reduction in urine leakage and improvement in quality of life observed in patients treated by nurse continence advisors and urogynaecologists were similar at 12 weeks and 2 years, but lower costs arose from treatment provided by nurse advisors. We suggest that conservative treatment by the nurse continence advisor could be used more widely in mild to moderate incontinence.
Phytoestrogens: the biochemistry, physiology, and implications for human health of soy isoflavones. The American Journal of Clinical Nutrition Open clinical study of effects of pumpkin seed extract/soybean germ extract mixture-containing processed food on nocturia
- K D R Setchell
- H Sogabe
- T Terado
Setchell, K. D. R. (1998). Phytoestrogens: the biochemistry, physiology, and implications for human health of soy isoflavones. The American Journal of Clinical Nutrition, 68. Sogabe, H., & Terado, T. (2001). Open clinical study of effects of pumpkin seed extract/soybean germ extract mixture-containing processed food on nocturia. Japanese Journal of Medicine and Pharmaceutical Science, 46, 727–737.
Cucurbitae semen. Pumpkin seed
- M Wichtl
Wichtl, M. (2004). Cucurbitae semen. Pumpkin seed. In Herbal Drugs and Phytopharmaceuticals (pp. 170–172). Medpharm GmbH Scientific Publisher.