Article

Escin improves sperm quality in male patients with varicocele-associated infertility

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Abstract

To evaluate the efficacy of escin to improve sperm quality in Chinese male patients with varicocele-associated infertility. This study included 219 male patients with varicocele-associated infertility. These patients were randomly assigned into three groups: the control, the surgery and the escin group. 106 patients, with a mean age of 30 years old and a mean period of infertility of 5.0 years, were recruited in the escin group and a daily dose of 60mg (30mg every 12h) of escin was administered orally during an uninterrupted period of 2 months. The diameter of spermatic vein was also measured using color Doppler ultrasonography before and after treatment in the escin group. Patients in all groups took composite medicines favorable for sperm quality and semen were obtained and analyzed before and after treatment. In response to treatment, the improvement rates in sperm density in the control, the surgery and the escin group, were 38.5%, 68.8%, and 57.5%, respectively. The differences in the surgery and the escin groups were significant compared to that in the control group (68.8% or 57.5% vs. 38.5%, P<0.05). The improvement rates in sperm motility in the control, the surgery and the escin group were 46.2%, 77.1%, and 55.7%, respectively. Significant difference was only observed between the surgery and the control group (77.1% vs. 46.2%, P<0.05). In the escin group, when severity of varicocele was classified to mild, moderate or severe degree according to the diameter of the spermatic vein, the improvement rates in disease severity were higher in the mild (41.7% vs. 20.0%, P<0.05) and moderate severity subgroups (64.4% vs. 20.0%, P<0.05) when compared to that in the severe subgroup (20.0%). The improvement rate in disease severity was also higher in the moderate subgroup when compared to that in the mild subgroup (64.4% vs. 41.7%, P<0.05). During the period of treatment, only very low frequencies of mild adverse effects were observed, most of which resolved without further symptomatic drug therapy after advising the patients to take escin after meal. Escin has little effect on vital signs, blood counts, liver or kidney function. Escin is a safe and effective drug to improve sperm quality in Chinese male patients with varicocele-associated infertility.

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... The herb was shown to target OS, resulting in an increase in sperm motility, density, and normal sperm morphology. In addition, Escin significantly improved the severity of varicocele [120]. These results were similar to those of an older study in which infertile men treated with Bu-Zhong-yi-qi-tang for 3 months experienced an increase in sperm concentration and motility [121]. ...
... Another herb, Rou Cong Rong, was shown to promote the sperm generating functions of the testes as well as improve the microenvironment of epididymis. Peng et al. [115] Tu Si Zi Improved sperm motility Liu et al. [116] Mixed herbal (6 components) Increased viability, number of motile and progressive sperm, curvilinear velocity, average path velocity, and lateral head displacement Furuya et al. [121] Bu-Zhong-yi-qi-tang Increased concentration and motility Sun and Bao [122] Yikang Tang Improved sperm parameters and pregnancy rates Tijani et al. [123] Manix Improved sperm quality Ahmad et al. [119] Withania somnifera Decreased oxidative stress and increased levels of antioxidants Fang et al. [120] Escin Increased sperm motility, sperm density, and normal sperm morphology Yang et al. [109] Sheng Jing Zhongzi Tang Improved spermatic density, motility, percentage of normal spermatid morphology, and pregnancy rates Yang et al. [109] Rou Cong Rong Increased sperm generation in testes Abdillahi and van Staden [113] Mixed herbal Increased serum testosterone levels Wang et al. [114] Wuziyanzong herbal pill Increased sperm density and improved sperm viability ...
... Herbal treatments may become a more important factor in treating male infertility in the future, and they have been shown to significantly increase sperm density and sperm viability [114]. Most research indicates that these supplements have little effect on vital signs, blood counts, and liver and kidney function [120], which may make them a safer option than some currently prescribed medications [125]. Herbal treatments may also offer a better and safer method to restore sex hormones in infertile men [119]. ...
... The herb was shown to target OS, resulting in an increase in sperm motility, density, and normal sperm morphology. In addition, Escin significantly improved the severity of varicocele [120]. These results were similar to those of an older study in which infertile men treated with Bu-Zhong-yi-qi-tang for 3 months experienced an increase in sperm concentration and motility [121]. ...
... Another herb, Rou Cong Rong, was shown to promote the sperm generating functions of the testes as well as improve the microenvironment of epididymis. Peng et al. [115] Tu Si Zi Improved sperm motility Liu et al. [116] Mixed herbal (6 components) Increased viability, number of motile and progressive sperm, curvilinear velocity, average path velocity, and lateral head displacement Furuya et al. [121] Bu-Zhong-yi-qi-tang Increased concentration and motility Sun and Bao [122] Yikang Tang Improved sperm parameters and pregnancy rates Tijani et al. [123] Manix Improved sperm quality Ahmad et al. [119] Withania somnifera Decreased oxidative stress and increased levels of antioxidants Fang et al. [120] Escin Increased sperm motility, sperm density, and normal sperm morphology Yang et al. [109] Sheng Jing Zhongzi Tang Improved spermatic density, motility, percentage of normal spermatid morphology, and pregnancy rates Yang et al. [109] Rou Cong Rong Increased sperm generation in testes Abdillahi and van Staden [113] Mixed herbal Increased serum testosterone levels Wang et al. [114] Wuziyanzong herbal pill Increased sperm density and improved sperm viability ...
... Herbal treatments may become a more important factor in treating male infertility in the future, and they have been shown to significantly increase sperm density and sperm viability [114]. Most research indicates that these supplements have little effect on vital signs, blood counts, and liver and kidney function [120], which may make them a safer option than some currently prescribed medications [125]. Herbal treatments may also offer a better and safer method to restore sex hormones in infertile men [119]. ...
... 18 Another extensively used Chinese agent, Escin, derived from seed extract of Aesculus hippocastanum, is an anti-inflammatory and anti-edema agent that enhances glucocorticoid and Prostaglandin F-2α (PGF-2α) activity and decreases Nuclear Factor-kappa β (NF-κβ) expression. 19 Fang et al. 20 compared 106 patients with clinical or subclinical varicocele-associated infertility who received escin 60 mg d -1 for two months with controls. All the patients received composite medicines favorable for sperm quality. ...
... Some of the studies reviewed in this article have shown sperm parameter improvement rates with placebo to be as high as 38%-46%. 20 In view of such data, unless large prospective trials are conducted, most such therapies will remain empirical. A number of studies reviewed in this manuscript provide a "proof of concept" or rationale for medical therapy to men with varicocele but fall short of providing true evidence. ...
Article
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Varicocele-associated male infertility has classically been managed using surgery or assisted reproductive techniques. With increasing evidence of oxidative stress as a pathophysiological factor in varicocele-associated infertility, medical therapy especially antioxidants might become a treatment option with lower risks. We reviewed the existing literature on the role of various medical agents in the management of male infertility attributed to varicoceles. Medical therapy is typically evaluated in three different situations such as (a) comparison of two drugs or one drug with placebo, (b) comparison of drugs versus surgery, and (c) comparison of drugs as adjuvant therapy with surgery versus drug therapy alone. Due to heterogeneity of data and lack of well-conducted studies, there is insufficient data to recommend routine use of medical therapy for men with varicocele-associated infertility and surgery remains the treatment of choice. Pregnancy and live birth rates are usually not reported in most studies and mere improvement in sperm parameters or antioxidant capacity is insufficient to support its routine use. Antioxidant therapy is a potential option due to its theoretical benefit, data from preclinical studies, and lack of major side effects. Adjuvant therapy with antioxidants after surgical repair of varicocele may improve the outcome and is a potential area for further research.
... P < 0.05) varicoceles than severe varicoceles (20%). 41 Ascorbic acid (Vitamin C) is a reactive oxygen species (ROS) scavenger that may protect sperm against oxidative DNA damage. 42 Alpha-tocopherol (Vitamin E) is also an antioxidant. ...
Article
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While we may be comfortable with an allopathic approach to male infertility, we are also responsible for knowledge about lifestyle modifications and holistic, complementary, and alternative therapies that are used by many of our patients. This paper provides an evidence-based review separating fact from fiction for several of these therapies. There is sufficient literature to support weight reduction by diet and exercise, smoking cessation, and alcohol moderation. Supplements that have demonstrated positive effects on male fertility on small randomized controlled trial (RCT) include aescin, coenzyme Q 10 , glutathione, Korean red ginseng, L-carnitine, nigella sativa, omega-3, selenium, a combination of zinc and folate, and the Menevit antioxidant. There is no support for the use of Vitamin C, Vitamin E, or saffron. The data for Chinese herbal medications, acupuncture, mind-body practice, scrotal cooling, and faith-based healing are sparse or inconclusive.
... There was a significant improvement of sperm density, but not motility, in the escin group when compared with the control group. Nonetheless, varicocelectomy is superior in improving semen parameters than the ecsin and control groups [85]. ...
Chapter
Despite being regarded as one of the most common causes of male subfertility, the pathophysiology of varicocele remains largely unknown. Recently, oxidative stress (OS) is proposed to be the mediator in how varicocele may negatively impact fertility. The imbalance of reactive oxygen species (ROS) and seminal antioxidants results in damage to sperm DNA and lipid membrane. There is evidence demonstrating higher OS level in men with varicocele which is also positively correlated with clinical grading of varicocele. Moreover, a number of studies have revealed the negative correlation between OS and conventional semen parameters. Furthermore, various interventions have shown their potential in alleviating OS in men with varicocele-associated infertility. Although direct evidence on improving pregnancy rate is not available at the moment, varicocelectomy has demonstrated promising results in relieving OS. Oral antioxidants represent another option with a favourable safety profile. The supplement can be used alone or as adjunct to varicocelectomy. However, most of the studies are hampered by heterogenous dose regime and high-level evidence is lacking.
... Few studies have analyzed a possible role of escin in male fertility. A Chinese study, evaluating the role of escin in varicocele-associated infertility, showed that a daily oral dose of 60 mg (30 mg every 12 h) for 2 months improved sperm concentration and caused changes in the diameter of the spermatic vein [82]. This dose is higher than the dose used for the venous insufficiency of other districts (orally: 40 mg daily; or intravenously: 5-10 mg daily). ...
Article
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The nonhormonal medical treatment can be divided into empirical, when the cause has not been identified, and nonempirical, if the pathogenic mechanism causing male infertility can be solved or ameliorated. The empirical nonhormonal medical treatment has been proposed for patients with idiopathic or noncurable oligoasthenoteratozoospermia and for normozoospermic infertile patients. Anti-inflammatory, fibrinolytic, and antioxidant compounds, oligo elements, and vitamin supplementation may be prescribed. Infection, inflammation, and/or increased oxidative stress often require a specific treatment with antibiotics, anti-inflammatory drugs, and/or antioxidants. Combined therapies can contribute to improve sperm quality.
... Other antioxidants that have been studied in a randomized controlled fashion are Escin and micronized purified flavonoid fraction (MPFF). Both studies showed statistically significant improvement in semen parameters such as sperm morphology and sperm motility and sperm density [31,32]. ...
Article
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Purpose of review: Varicocele may play a significant role in a subset of patients presenting with male factor infertility. Despite its relatively high prevalence amongst subfertile men, there has been controversy over the effectiveness of surgical treatments, patient selection, and when to administer treatment, particularly in the era of assisted reproductive technology. Recent findings: In line with earlier finding, recent evidence strongly suggests that varicocelectomy improves pregnancy rates and semen parameters. The currently available literature still does not clearly elucidate the answer to this question, due to flaws in retrospective study design. Patients undergoing subinguinal microsurgical varicocelectomy appear to have the highest pregnancy rates, and lowest complication rates, compared to other surgical approaches. Current research has given us a better understanding of the relationship between varicocele and infertility. Amongst men presenting with semen analysis abnormalities and varicoceles, including those patients presenting with non-obstructive azoospermia or couples with a significant male factor component failing previous attempts at in vitro fertilization, varicocelectomy may improve take home baby rates. More robust, prospective, controlled studies are needed to further clarify the population of subfertile men with varicocele most likely to benefit from varicocelectomy.
... Out of these 71 RCTs, 53 (75%) studied patients with idiopathic male infertility or sperm abnormality; eight (11%) investigated patients with varicocele-associated sperm abnormalities (Chen et al., 2020b;Fang et al., 2010;Geng et al., 2021;Guo et al., 2006;Linya et al., 2014;Sun et al., 2016;Yan et al., 2004;Zhang and Zhao, 2016), five (7%) examined patients with sperm abnormalities caused by autoantibodies (Fu et al., 2005;Lu et al., 2006;Pawłowicz et al., 2001;Qi et al., 2007;Yu et al., 2004), four (5.6%) were associated with microbial infection of sexual organs (Cai et al., 2012;Gao et al., 2013;Li et al., 2014;Sun et al., 2006), which the remaining one (1.4%) focused on patients with oligoasthenospermia caused by hyperprolactinemia . ...
Article
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Background : Male factor infertility often results from testicular disorders leading to inadequate sperm quantity and quality. Both beneficial and detrimental effects of botanical products, especially herbal medicines, on testicular functions and male fertility have been reported in the literature. Purpose : This scoping review aims to map the main clinical evidence on the different impacts of botanical entities on the testis and to critically appraise relevant randomized controlled trials (RCTs) published in the recent 5 years, so as to inform the future. Methods : Systematic reviews, meta-analyses and RCT reports on botanical impacts on testicular functions and male fertility were retrieved and synthesized from Pubmed, Web of Science, Scopus, Embase, ProQuest, Cochrane Library and Google Scholar up to 10th May 2022. RCTs published since 2018 were critically appraised against good practice guidelines for RCT and for reporting herbal studies. Results : We identified 24 systematic reviews and meta-analyses published since 2005, by authors from Iran (25%), China (21%), USA (12.5%) and 9 other countries. All but two were published in English. Only 3 systematic review protocols were identified, all published in English from China in the recent 3 years. We identified 125 RCTs published in six languages, mainly English (55%) and Chinese (42%). They were published since 1994 from 23 countries on all the six inhabitable continents, with China (46%), Australia (8%), USA (8%), India (7%) and Iran (5%) being the leading contributors. 72% and 28% RCTs published in English were on efficacy (botanicals vs placebo) and comparative effectiveness (one botanical vs other treatments), respectively. In contrast, 98% RCT reports in Chinese were on comparative effectiveness, with merely 2% on efficacy. Among all the 125 RCTs, 57% were studies in men with semen abnormality and/or male infertility, 22% investigated herbal effects in healthy men, 14% were in men with male sexual dysfunction and hypogonadism, and 7% were conducted in men with non-sexual disorders. Since 2018, 32 RCTs have been published, in English (69%) or Chinese (31%). Nineteen RCT reports from China, India, Japan and Korea all studied herbal formulae while the 13 RCT reports from Australia, Brazil, Czech and Italy, Iran, Malaysia, Spain, the UK and the USA all exclusively studied extracts of a single species. Putting geo-cultural differences aside, gossypol and extracts of Tripterygium wilfordii Hook. f. were found to be detrimental to the testis and male fertility, while the extracts of Withania somnifera (L.) Dunal and traditional Chinese medicine Qilin Pill, etc., might improve testosterone levels and semen parameters, thus could be therapeutic for male sexual dysfunction and infertility. However, all still require further evaluation in view of recurring weaknesses in quality control of herbal materials, RCT design and reporting. For example, only 9%-23% of the RCTs published since 2018 provided information on voucher samples, chemical profiling, herbal authentication and herbal extraction. Conclusion : Research on botanicals and the testis has been reported worldwide, demonstrating clear geo-cultural differences in studied plant species, botanical types, study objectives and quality of research design, implementation and reporting. Due to a few recurring weaknesses in the literature, this study is unable to recommend the use of any specific botanicals, however, current evidence does indicate that botanicals can be double-edged swords to the testis and male fertility. To secure better clinical evidence, future studies must faithfully implement existing and emerging good practice guidelines.
... Two independent reviewers evaluated the remaining 197 potentially relevant trials of which 175 were deemed to be relevant. From these, the largest 100 RCTs reporting data from 24 542 men (range: 80-2772 men) were used to identify and report outcomes (Abdel-Maguid and Othman, 2010;Fang et al., 2010;Fayez et al., 2010;Kovacic et al., 2010;Abdel-Meguid et al., 2011;Azadi et al., 2011;Balaban et al., 2011;Figueira Rde et al., 2011;Hafeez et al., 2011;Safarinejad, 2011;Safarinejad et al., 2011;Selice et al., 2011;Turhan et al., 2011;Wilding et al., 2011;Amirzargar et al., ...
Article
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Abstract STUDY QUESTION What are the primary outcomes and outcome measures used in randomised controlled trials (RCTs) evaluating potential treatments for male infertility in the last 10 years? SUMMARY ANSWER Outcome reporting across male infertility trials is heterogeneous with numerous definitions and measures used to define similar outcomes. WHAT IS KNOWN ALREADY No core outcome set for male infertility trials has been developed. Male infertility trials are unique in that they have potentially three participants, a man, a female partner and their offspring and this will likely lead to significant variation in outcome reporting in randomised trials. STUDY DESIGN, SIZE, DURATION A systematic review of RCTs mapping outcomes and outcome measures evaluating potential treatments for men with infertility registered in the Cochrane Register of Controlled Trials (CENTRAL) between January 2010 and July 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS Abstract screening and study selection was undertaken in duplicate using a review protocol that was developed prior to commencing the review. No risk of bias assessment was undertaken as this review aims to report on outcome reporting only. MAIN RESULTS AND THE ROLE OF CHANCE One hundred and seventy-five RCTs were identified, and given the large number of studies we limited our review to the 100 largest trials. Seventy-nine different treatments were reported across the 100 largest RCT including vitamin and dietary supplements (18 trials), surgical treatments (18 trials) and sperm selection techniques (22 trials). When considering the largest 100 trials (range: 80 to 2772 participants), 36 primary and 89 secondary outcomes were reported. Forty-seven trials reported a primary outcome and 36 trials clearly defined their primary outcome. Pregnancy outcomes were inconsistently reported and included pregnancy rate (51 trials), pregnancy loss including miscarriage, ectopic pregnancy, stillbirth (nine trials), and live birth (13 trials). Trials consistently reporting the same outcome frequently used different definitions. For example, semen quality was reported by 75 trials and was defined in seven different ways, including; the World Health Organization (WHO) 2010 criteria (32 trials), WHO 1999 criteria (18 trials), WHO 1992 criteria (three trials), WHO 1999 and 1992 criteria (one trial), and the Kruger strict morphology criteria (one trial).
... 2 Numerous studies have targeted the issue of varicocele-associated infertility. 3,4 The belief that it is not linked to male infertility is based on reviews of prospective randomized studies in which varicocele repair was concluded to be an ineffective treatment for male subfertility 5,6 and research demonstrating no significant improvement in semen parameters, sperm morphology, or motility following ligation of the testicular veins in infertile couples in which the male partner presented with varicocele. 7 However, surgical correction of varicocele by varicocelectomy was reported to cause a 70% improvement in semen quality in 986 subfertile men, and a preoperative sperm count .10 million per mL was associated with a better outcome. ...
Article
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The effectiveness of varicocelectomy in restoration of fertility and improvement of semen parameters is still controversial. The purpose of this study was to determine the effect of age on semen parameters following varicocelectomy in a group of infertile men. Improvements in sperm count, morphology, and motility were studied in 67 infertile patients 4-10 months after varicocelectomy. The mean age of the patients was 30.48 ± 7.49 years. Significant improvements in total sperm count, percentage normal morphology, and motility were noted in all age groups (P < 0.05). Patients aged <25 years demonstrated the greatest increase in sperm counts, normal morphology, and motility following varicocelectomy. There was a significant negative correlation between age and sperm count, sperm morphology, and sperm motility (P < 0.05). The effect of age on improvement in sperm parameters after varicocelectomy is inconsistent with some reports in the literature, and could be attributable to the duration of infertility prior to surgery; in the long term, varicoceles are known to have deleterious effects on testis biology.
... Two independent reviewers evaluated the remaining 197 potentially relevant trials of which 175 were deemed to be relevant. From these, the largest 100 RCTs reporting data from 24 542 men (range: 80-2772 men) were used to identify and report outcomes (Abdel-Maguid and Othman, 2010;Fang et al., 2010;Fayez et al., 2010;Kovacic et al., 2010;Abdel-Meguid et al., 2011;Azadi et al., 2011;Balaban et al., 2011;Figueira Rde et al., 2011;Hafeez et al., 2011;Safarinejad, 2011;Safarinejad et al., 2011;Selice et al., 2011;Turhan et al., 2011;Wilding et al., 2011;Amirzargar et al., ...
... Currently, extracts from horse-chestnut seeds are widely used to treat peripheral vascular disorders including chronic venous insufficiency, haemorrhoids and post-operative oedema (Dickson, Gallagher, McIntyre, Suter, & Tan, 2004;Dudek-Makuch & Studzińska-Sroka, 2015;Facino, Carini, Stefani, Aldini, & Saibene, 1995;Gurel et al., 2013;Pittler & Ernst, 1998;Ruffini, Belcaro, Cesarone, & Dugall, 2004;Suter, Bommer, & Rechner, 2006;Underland, Saeterdal, & Nilsen, 2012), as a preventative of dental plaque and periodontitis in toothpaste (Aravind, Lakshmi, & Arun, 2012;Kim et al., 2017), and to counter male infertility by improving sperm quality (Fang et al., 2010). Saponin extracts have been used to prevent colon cancer in rats (Szabadosova et al., 2013) and may also reduce growth of tumours in a number of cancers in humans (Cheong et al., 2018;Geran, Greenberg, McDonald, Schumacher, & Abbott, 1972;Turkekul et al., 2018). ...
Article
This account presents information on all aspects of the biology of Aesculus hippocastanum L. (horse-chestnut) that are relevant to understanding its ecological characteristics and behaviour. The main topics are presented within the standard framework of the Biological Flora of the British Isles: distribution, habitat, communities, responses to biotic factors, responses to environment, structure and physiology, phenology, floral and seed characters, herbivores and disease, history and conservation. Aesculus hippocastanum is a large deciduous tree native to the Balkan Peninsula. Native populations are small (<10,000 trees total) and apparently in decline, but the tree has been widely planted in gardens and streets across Europe and other temperate areas from the 17th century onwards. It was voted the UK's favourite tree in a 2017 poll. As a British neophyte, it is occasionally naturalised in open wooded habitats. Horse-chestnut is renowned for the beauty of its large (up to 30 cm long), upright panicles of white flowers, and for the large seeds (up to 42 g each) used in the formerly common children's game of “conkers.” More recently, the triterpene glycosides, extractable from various plant parts but especially the seeds, have been widely used in medicine. In much of Europe, horse-chestnut is affected by chestnut bleeding canker (caused by Pseudomonas syringae pv. aesculi), the horse-chestnut leaf miner Cameraria ohridella and the leaf blotch fungus Guignardia aesculi. The canker is likely to lead to death of <10% individuals, but seeds of plants infested with the leaf miner are 40%–50% smaller, which may affect long-term establishment in non-planted areas. © 2019 The Authors. Journal of Ecology
Article
This study was conducted to investigate the effects of aescin treatment in a rodent model treated with an experimentally induced varicocele. Experimental varicocele was induced by partial ligation of the left renal vein of rats. Aescin administration was performed daily for 4 weeks after the varicocele induction. Seven weeks later, a contrast-enhanced ultrasound was performed of the rats' testis to assess testicular blood flow. The animals were sacrificed, and H&E staining was then used to evaluate testicular pathological changes and polymorphonuclear leucocytes density. Cauda epididymal sperm counts and motility were evaluated. Blood was collected for the measurement of follicle-stimulating hormone, luteinising hormone and testosterone. Contrast-enhanced ultrasound showed that there were significant decreases in testicular blood flow in the aescin-treated groups compared with those in control varicocele group. Testicular oedema was detected in those rats treated with a varicocele but without aescin, while no oedema was found in the experimental group. H&E staining showed dysfunctional spermatogenesis in both cohorts; however, polymorphonuclear leucocytes density was significantly reduced in aescin-treated groups. There was an increase in sperm counts of the aescin-treated groups. Our study demonstrated that aescin could exert therapeutical effects on reversal of testicular lesions in varicocele rats.
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Ethnopharmacological relevance: Adequate pharmacokinetic data of escin, a natural mixture of triterpene saponins used for the treatment of chronic venous insufficiency, hemorrhoids, inflammation and edema, is of special interest in view of the growing use of escin agent in clinical medicine. However, pharmacokinetic data are inadequate to support their clinical indication. Escin Ib and isoescin Ib are the chief active ingredients in escin, pharmacokinetics study of them would be helpful for improving the practice of escin application. The goals of this study are to determine the plasma concentration of escin Ib and isoescin Ib using an established liquid chromatography tandem mass spectrometry (LC-MS/MS) method and to compare the pharmacokinetics and bioavailability of these compounds in rats when administered as pure isomers or as sodium escinate. Materials and methods: Five groups of Wistar rats (n=6 per group) were treated with either an intravenous (IV) dose (2.78mg/kg) of sodium escinate (corresponding to 0.5mg/kg of escin Ib and 0.5mg/kg of isoescin Ib), an IV dose (0.5mg/kg) and an oral dose (4mg/kg) of pure escin Ib or isoescin Ib. The concentrations of escin Ib and isoescin Ib in rat plasma were determined by LC-MS/MS at various times following the administration of the drugs. The pharmacokinetic parameters were estimated by a non-compartmental analysis and then subjected to statistical analysis. Results: The administration of sodium escinate, which contains the two isomers, gave rise to higher terminal phase half-life (t1/2) and mean residence time (MRT) values for both escin Ib and isoescin Ib compared to the corresponding compounds administered alone. The absorption of escin Ib and isoescin Ib was very poor, with the oral bioavailability (F) values of <2% observed for both compounds. The two compounds were found to isomerize in vivo, wherein the conversion of escin Ib to isoescin Ib was much easier than that of isoescin Ib to escin Ib. Conclusions: A comparison of the pharmacokinetics of escin Ib and isoescin Ib administered alone and together in rats suggests that the administration of herbal preparations of escin in a clinical setting may result in a longer duration of action than the administration of each isomer alone. The interconversion of escin Ib and isoescin Ib when administered alone indicates that the administration of one isomer results in exposure to the other isomer.
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A rapid and sensitive LC–MS–MS method for the simultaneous determination of escin Ia and isoescin Ia in rat plasma, urine, feces and bile samples was developed and validated. Analytes and telmisartan [internal standard (IS)] were extracted by solid-phase extraction on C18 cartridges. Components in the extract were separated on an HC-C18 column (5 μm, 150 × 4.6 mm i.d.) using 10 mM ammonium acetate–methanol–acetonitrile (40:30:30, v/v/v) as the mobile phase. The method demonstrated good linearity from 5 ng mL−1 (LLOQ) to 1,500 ng mL−1 for both escin Ia and isoescin Ia. Intra- and inter-day precision measured as RSD was within ±15%. Recoveries and matrix effects of both escin Ia and isoescin Ia were satisfactory in all four matrices examined. The method was successfully applied to a pharmacokinetic study in Wistar rats after a single intravenous administration of escin Ia at the dose of 1.0 mg kg−1
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The protective effects of tripterygium glycoside-loaded solid lipid nanoparticles (TG-SLNs) on male reproductive toxicity were investigated in rats. Thirty-six male Sprague-Dawley rats were randomly divided into three groups of 12: control group, tripterygium glycoside (TG) group, and TG-SLN group. After the animals had been orally administered with the substances for 28 consecutive days, their sperm count and sperm motility, organ coefficients, serum testosterone levels, testicular ultrastructure, and reproductive ability were observed. The results showed that the sperm motility rate in the TG group was only 3%, whereas the rates in the TG-SLN and control groups were 33% and 71%, respectively. Compared with those in the control group, the motion counts of path velocity, track speed, progressive velocity, straightness, linearity, beat cross frequency, amplitude of lateral head displacement, and sperm concentrations in the TG-SLN group were not significantly different while those in the TG group significantly decreased (p < 0.01). TG-SLNs did not cause testicular atrophy and instead maintained normal serum testosterone levels. The effect of TG-SLNs on the testicular ultrastructure was very evident; the morphologies of Sertoli, spermatogonial, mitochondrial, and sperm cells were normal. In terms of reproductive ability, one rat (17%) from the TG-SLN group and five rats (83%) from the control group became pregnant, whereas none of the rats from the TG group became pregnant. These data indicate that TG-SLNs have potentially protective effects on male reproductive toxicity in rats.
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Ethnopharmacological relevance: Escin, a natural mixture of triterpene saponins, is commonly utilized for the treatment of chronic venous insufficiency, hemorrhoids, inflammation and edema. Escin Ia is the chief active ingredient in escin and plays key role in mediating its pharmacological effects. Adequate pharmacokinetic data are essential for proper application of escin agent in clinical practice. However, pharmacokinetic properties of escin Ia are still poorly understood and this conflicts with the growing use of escin agent over the years. The goal of this study is to investigate the pharmacokinetic behavior of escin Ia in rats after low, medium and high-dose intravenous administration. Materials and methods: Wistar rats were divided into 3 groups (n=6 per group) and escin Ia was administered via the caudal vein at doses of 0.5, 1.0 and 2.0 mg/kg, respectively. Subsequently, the concentrations of escin Ia and its metabolite isoescin Ia, a positional isomer of escin Ia, in rats׳ plasma were measured by an established liquid chromatography tandem mass spectrometry (LC-MS/MS) method at various time points following the administration of the drug. Main pharmacokinetic parameters were calculated by non-compartmental analysis using the TopFit 2.0 software package (Thomae GmbH, Germany). Results: After intravenous administration, the Cmax and AUC of escin Ia increased in a dose-proportional manner at the dose of 0.5 mg/kg and 1.0 mg/kg, while increased in a more than dose-proportional manner at the doses of 1.0 mg/kg and 2.0 mg/kg. The t₁/₂ was significantly longer with increased intravenous doses, while other parameters such as CL and Vd also exhibit disagreement among three doses. Taken together, our data showed dose-dependent pharmacokinetic profile of escin Ia in rats after intravenous administration at the doses of 0.5-2.0 mg/kg. After intravenous administration, escin Ia was rapidly and extensively converted to isoescin Ia. Conclusions: The results suggested dose-dependent pharmacokinetics of escin Ia at the doses of 0.5-2.0 mg/kg after intravenous administration. Escin Ia is isomerized to isoescin Ia rapidly and extensively regardless of the doses.
Article
Background: Varicocele is defined as dilated and twisted veins of the pampiniform plexus in the spermatic cord. It is the most common cause of male infertility. There are various medical and surgical procedures for the treatment of this disease. Aim: This study was aimed to compare the effects of oral administration of L-Carnitine and varicocelectomy on spermogram parameters. Materials and methods: This study was conducted as a double blind clinical trial without randomization. Inclusion criteria were, all married infertile men with varicocele. Patients chose their treatment personally and spermogram was carried out for all patients before and after the third and sixth months of treatment. Then, the sperm parameters of the two groups were compared using repeated measures ANOVA. Results: In our study, trend of sperm count in the surgery group changed from 22 to 28.61 million (vs 34.6 to 45.37 in L-Carnitine group), motility changed from 21.74 to 35.38 percent (vs 33.9 to 47.48 in L-Carnitine group), normal sperm morphology changed from 46.25 to 60 percent (vs 56.61 to 69.7 in L-Carnitine group) and volume of semen changed from 3.5 to 4.17 cc (vs 2.95 to 4.33 in L-Carnitine group). These values were not statistically different between the two groups. Conclusion: Based on the results of this study, we can say that medicinal treatment by administration of oral L-Carnitine is as effective as varicocelectomy in improving semen parameters and can be used as an alternative to surgery for varicocele grade II.
Article
Phytotherapy belongs to the area of complementary and alternative medicine (CAM) and the definition of phytotherapy is the use of plants or plant extracts for medicinal uses. Interest in phytotherapy is growing in both Asian and western countries for its use in the prevention and management of disease, improvement of general health and anti-aging. And also, there are several studies about the efficacy of phytotherapy in urologic diseases like benign prostatic hyperplasia (BPH), erectile dysfunction (ED), late-onset hypogonadism (LOH) and infertility in males. Phytotherapy for BPH including saw palmetto, pygeum, and nettles, is under vigorous research for the therapeutic effect. No solid evidence showing better effective treatment modality for ED than placebo has been found yet for phytotherapy. Recently, a potent NO donor, L-arginine is under research with promising results. Phytotherapy is used by a number of patients with urological disease, and urologists need to have accurate knowledge about phytotherapy as well as keep a cautious approach. The possible effects and side effects should be defined and related to urologic patients by urologists.
Article
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Background: Varicocele is defined as dilated and twisted veins of the pampiniform plexus in the spermatic cord. It is the most common cause of male infertility. There are various medical and surgical procedures for the treatment of this disease. Aim: This study was aimed to compare the effects of oral administration of L-Carnitine and varicocelectomy on spermogram parameters. Materials and Methods: This study was conducted as a double blind clinical trial without randomization. Inclusion criteria were, all married infertile men with varicocele. Patients chose their treatment personally and spermogram was carried out for all patients before and after the third and sixth months of treatment. Then, the sperm parameters of the two groups were compared using repeated measures ANOVA. Results: In our study, trend of sperm count in the surgery group changed from 22 to 28.61 million (vs 34.6 to 45.37 in L-Carnitine group), motility changed from 21.74 to 35.38 percent (vs 33.9 to 47.48 in L-Carnitine group), normal sperm morphology changed from 46.25 to 60 percent (vs 56.61 to 69.7 in L-Carnitine group) and volume of semen changed from 3.5 to 4.17 cc (vs 2.95 to 4.33 in L-Carnitine group). These values were not statistically different between the two groups. Conclusion: Based on the results of this study, we can say that medicinal treatment by administration of oral L-Carnitine is as effective as varicocelectomy in improving semen parameters and can be used as an alternative to surgery for varicocele grade II.
Article
The aim of this study was to uncover the protective effect of berberine (BBR), an antioxidant chemical, on experimental varicocele (VCL)-induced adverse effects on cell cycle machinery during early germ cells mitosis. To follow-up this study, 30 mature male Wistar rats were divided into control-sham, nontreated VCL, 50 mg kg−1 and 100 mg kg−1 BBR-treated VCL groups. Following 60 days, histological alterations were analysed by haematoxylin and eosin (H and E) staining, and expressions of cyclin-D1, cyclin-dependent kinase-4 (cdk4) and p21 were investigated by immunohistochemical (IHC) staining technique. Finally, DNA ladder test was carried out to examine the testicular DNA fragmentation. Administration of BBR remarkably diminished the percentage of seminiferous tubules with deformed shape, depleted germ cells and germ cells dissociation compared to VCL-sole group. The IHC observations showed that BBR significantly (p < .05) reduced VCL-induced p21 expression increase and up-regulated cyclin-D1 and cdk4 expressions. Moreover, BBR decreased VCL-induced DNA fragmentation. In conclusion, BBR can promote cell cycle through cellular DNA content protection, p21 expression down-regulation and maintaining cyclin-D1 and cdk4 expressions. Thus, BBR could be considered as a novel protective biochemical agent against experimental VCL-induced derangements. However, more studies are needed to uncover BBR-induced effects on cells cycle process and germ cells development.
Chapter
Even if varicocele is considered as one of the first known causes of male infertility, to date, it is still under debate if varicocele repair is able to improve fertility.
Article
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هر چند رابطه احتمالی بین ناباروری مردان و اختلال های سیستمیک مثل مشکلات اونکولوژیک، بیماری های قلبی ـ عروقی، اختلال های متابولیک و بیماری های اتوایمیون همواره مد نظر متخصصان درمان ناباروری قرار داشته است، لیکن کاهش شانس باروری و حتی بروز ناباوری در مردان همواره نشــانه ای از آســیب به ســلامت عمومی ایشــان و نتیجه مواجه های غیرطبیعی با عوامل آلاینده زیســت محیطی و سبک زندگی ناسالم نیز بوده اســت به علاوه، دلایل ژنتیکی و مواجه های دوران جنینی مردان نابارور از طریق بندناف نیز به عنوان دلیل دیگری جهت بروز این اختلال جدی با پیامد آسیب عمومی به سلامت مردان مطرح گردیده است. اگرچه رویکرد مستقیم به استفاده از درمان های دارویی و غیردارویی در افزایش میزان باروری مردان مسیری معمول و جاافتاده در علم پزشکی است، نگرشی عمیق تر از زاویه نقش سموم در بروز این اختلال و نگاهی بنیادی به عوامل مرتبط با سبک زندگی از سویی در تعیین اتیولوژی و پیشگیری از بیماری حایز اهمیتی ویژه است. علاوه بر این که اســتفاده از طب مکمل نیز با تعدیل اثرات ســموم و آلاینده ها می تواند در کاهش آسیب به سلامت عمومی بیماران نابارور و تقویت کارآیی و اثر بخشــی روش های درمانی موجود و متداول مؤثر باشد. در این راستا، هدف از نگارش این مقاله، مروری اجمالی و مبتنی بر شواهد در خصوص سبک زندگی و افزایش خطر ناباروری مردان از یک ســوی و ارزیابی اثربخشی درمان های مکمل و نوین از سوی دیگر است. در واقع، این مقاله مروری است به نقش سبک زندگی مثل کاهش وزن با رژیم و ورزش، ترک ســیگار، کاهش مصرف الکل و تغذیه از یک سوی و نقش مصرف مکمل های گیاهی از جمله ،2 ، کیوتن، گلوتاتیون، جین ســینگ قرمز، ال کارنیتین، سیاه دانه 1 مکمل های حاوی شــاه بلوط (آزین) ، ســلنیوم، زینک ـ فولات ـ آنتی اکســیدان ها در افزایش میزان باوری مردان نابارور از سوی 3امگا ، زعفران، E، ویتامین C دیگر. در ادامه در این مقاله اطلاعات موجود در خصوص کاربرد های ویتامین معنویت درمانی، هنردرمانی و موسیقی درمانی را نیز خواهید خواند.
Article
Background: Varicocoele-induced male infertility potentially involves oxidative stress. Although varicocoelectomy is recommended for varicocoele patients presenting abnormal semen findings, no pharmacotherapeutic methods currently exist. We have recently developed a silicon-based agent that produces hydrogen by the reaction with water. Objectives: This study aimed to investigate the therapeutic effects of oral administration of a Si-based agent on varicocoele rat. Materials and methods: Twenty-one rats were divided into four groups: varicocoele + normal diet (n = 5), varicocoele + Si-based agent-supplemented diet (n = 6), sham + normal diet (n = 5), and sham + Si-based agent-supplemented diet (n = 5). All rats were euthanized four weeks after surgery. Results: The mean left epididymal sperm motility was 74.4% in the sham group, 72.3% in the sham + Si group, 57.6% in the varicocoele group, and 66.9% in the varicocoele + Si group. Epididymal sperm motility was significantly lower in the varicocoele group, but was significantly higher upon Si-based agent ingestion (P < .01). The mean left testicular weight, Johnsen's score, and left epididymal sperm concentration did not differ significantly between groups. The 8-OHdG concentration and DNA fragmentation rate were significantly increased in the varicocoele group, but were significantly decreased in the Si-based agent intake group (P < .01). Additionally, the IVF rate was significantly lower in the varicocoele group (26.3%) compared with the sham group (73.4%; P < .01), and was significantly higher in the varicocoele + Si group (51.8%) compared with the varicocoele group (P < .05), indicating that the Si-based agent improves IVF rates. Discussion and conclusion: Oral intake of the silicon-based agent improves epididymal sperm motility and in vitro fertilization rates through hydrogen production and subsequent reduction of oxidative stress. Considering the lack of effective noninvasive methods, this Si-based agent is potentially applicable for treating varicocoele-induced abnormal semen parameters.
Chapter
Horse chestnut (Aesculus hippocastanum) is a species of flowering plant in the Sapindaceae family with clinical evidence for chronic venous insufficiency (CVI). In addition to benefits for CVI, clinical trials indicate that horse chestnut seed extract (HCSE) or its constituent escin may be beneficial for hearing loss and varicocele-related infertility. Escin has been shown to have anti-inflammatory, neuroprotective, and antitumor effects. HCSE has venotonic, vascular protective, antispasmodic, anti-edematous, anti-allergic, anti-inflammatory, astringent, vasodilator, bitter, and diuretic properties. This chapter examines some of the scientific research conducted on horse chestnut, both alone and in combination formulas, for treating numerous health conditions. It summarizes results from several human studies of horse chestnut’s use in treating ENT, cardiovascular, genitourinary, and dermatologic disorders. Finally, the chapter presents a list of horse chestnut’s active constituents, different Commonly Used Preparations and Dosage, and a section on “Safety and Precaution” that examines side effects, toxicity, and disease and drug interactions.
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An inflammation of the cutis and subcutis of the external auditory canal is a primary symptom in cases of acute otitis externa. It is usually treated locally, since this type of therapy ensures a high concentration of the drug and interacts at the site of inflammation with no systemic effects. This systematic review compares the efficacy of treatment using a ciprofloxacin 0.2% solution with other therapeutic options. After compiling a catalog of search terms, medical databases were searched systematically for randomized, controlled studies. This search initially yielded a total of 38 studies which were then evaluated by three independent reviewers. The number of studies was subsequently reduced to 14: six studies using a ciprofloxacin 0.2% solution, and eight studies using both 0.2% and 0.3% solutions. The studies included in the review demonstrate the statistical equivalence between the ciprofloxacin solution (0.2%) and the reference products PNH (a combination of polymyxin B, neomycin sulfate and hydrocortisone), auriculum powder, and a ciprofloxacin foam with respect to the cure rate. The research groups consistently observed high in vitro activity of ciprofloxacin against Pseudomonas aeruginosa. This systematic review confirms the hypothesis of ciprofloxacin's noninferiority in the treatment of otitis externa, in terms of the cure rate and microbiological eradication.
Article
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We examined the effect of 12 weeks of daily oral administration of pentoxifylline with zinc and folic acid on the semen quality of 36 men with varicocele-associated infertility in an open, uncontrolled study. After 4 weeks of treatment, the proportion of morphologically normal sperm cells was significantly increased; these changes persisted until at least 4 weeks after the end of treatment.
Article
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Treatment of varicoceles became the most common treatment for male infertility merely on an empirical basis. However, in the age of evidence-based medicine it is surprising that only a few, and mainly recent, randomized controlled clinical trials with relevant outcome parameters have been published to allow adequate judgement of treatment effectiveness. Moreover, difficulties in study design could also be detected in most of these high-quality studies. Despite these difficulties and in contrast to the majority of uncontrolled studies on varicocelectomy, meta-analysis of these randomized controlled clinical studies involving 385 patients showed no significant treatment benefit and questions the common practice of varicocelectomy. Even the high-quality studies show conflicting results and therefore the topic of varicocele treatment will remain controversial and further randomized clinical trials should readdress this issue. For the time being, intervention by surgical or angiographic occlusion of the spermatic vein cannot be recommended.
Article
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Background: Conservative therapy of chronic venous insufficiency (CVI) consists largely of compression treatment. However, this often causes discomfort and has been associated with poor compliance. Therefore, oral drug treatment is an attractive alternative. Objectives: To review the evidence from rigorous clinical trials assessing the efficacy and safety of oral horse chestnut seed extract (HCSE) versus placebo, or other treatments for CVI. Search strategy: Randomised controlled trials (RCTs) of HCSE for chronic venous insufficiency were sought through EMBASE (inception to December 2001), MEDLINE and AMED (from inception to February 2004), The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 1, 2004), the Specialised Trials Register of the Cochrane Peripheral Vascular Diseases Group (last searched February 2004), and Phytobase (from inception to January 2001, no longer operational). Manufacturers of HCSE preparations and experts on the subject were contacted for published and unpublished material. There were no restrictions on language. Selection criteria: RCTs were included if they compared oral HCSE mono-preparations with placebo, or other treatments, in patients with CVI. Trials assessing HCSE as one of several active components in a combination preparation, or as a part of a combination treatment, were excluded. Data collection and analysis: Two reviewers independently selected and assessed methodological quality of the studies using a standardised scoring system, and extracted data. Disagreements concerning evaluation of individual trials were resolved through discussion. Main results: Overall, there appeared to be an improvement in CVI related signs and symptoms with HCSE compared with placebo. Leg pain was assessed in seven placebo-controlled trials. Six reported a significant reduction of leg pain in the HCSE groups compared with the placebo groups, while another reported a statistically significant improvement compared with baseline. One trial suggested a weighted mean difference (WMD) of 42.4 mm [95% confidence interval (CI) 34.9 to 49.9] measured on a 100 mm visual analogue scale. Leg volume was assessed in six placebo-controlled trials. Meta-analysis of five trials (n = 289) suggested a significant reduction in favour of HCSE compared with placebo (WMD 56.3 ml [95% CI 24.1 to 88.5]). One trial indicated that HCSE may be as effective as compression stockings at reducing leg volume. Adverse events were usually mild and infrequent. Reviewers' conclusions: The evidence presented implies that HCSE is an efficacious and safe short-term treatment for CVI. However, several caveats exist and more rigorous RCTs are required to assess the efficacy of this treatment option.
Article
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The triterpene saponin escin is the active component of the extract of seeds of Aesculus hippocastanum used in the treatment of chronic venous insufficiency. Escin is also used experimentally to increase membrane permeability in isolated cells. Since endothelial dysfunction is postulated to be involved in venous insufficiency, the possible endothelium-protectant effect of escin was explored in rat aortic rings, a model widely used to study such effects with cardiovascular agents. Escin enhanced endothelium-dependent relaxation induced by acetylcholine when such relaxation had been reduced by exposure to the superoxide ion generator pyrogallol. This effect was attributed to enhanced nitric oxide production by endothelial nitric oxide synthase, a calcium-dependent enzyme, activated by the increased endothelial cell permeability to calcium induced by escin. Another effect of escin thought to contribute to its therapeutic activity is its ability to produce venous contraction. The compound was found to induce concentration-related contraction also in rat aortic rings. This response was partially inhibited by removal of the endothelium or by preincubation with indomethacin, and was completely abolished by incubation in a calcium-free perfusion fluid. Contraction was considered to be due mainly to the aforementioned effect on calcium permeability, with some mediation by release of endothelial vasoconstrictor prostanoids. It was concluded that, in rat aorta, escin possesses an endothelium-protectant action and a direct contractile effect. The former could contribute to its beneficial effect in the treatment of venous insufficiency, while the latter could constitute a limiting side effect.
Article
To ascertain whether a nonsteroidal anti-inflammatory drug (cinnoxicam) or surgical varicocelectomy are suitable therapies for oligoasthenospermia associated with varicocele. Patients who were oligoasthenospermic and had a varicocele were blindly randomized into three groups and the varicocele graded using echo-colour Doppler ultrasonography. In group 1, seven men had grade V, four grade IV and 30 grade III varicoceles; in group 2 eight had grade V, 10 grade IV and 43 grade III; in group 3 six had grade V, eight grade IV and 40 grade III. Group 1 underwent surgery, group 2 received cinnoxicam (one 30 mg suppository every 4 days for 12 months) and group 3 received a placebo (one glycerine suppository every 4 days for 12 months). Sperm was analysed at intervals to follow the response in the three groups, and any side-effects considered. Surgery significantly increased sperm values in men with grade III-V varicocele within 4 months, the highest values being obtained at 8 and 12 months. Cinnoxicam significantly improved sperm quality after 2 months in men with grade III varicocele, but the results were best at 4 months and stable at 12 months; stopping therapy caused a decline to the baseline values. Cinnoxicam did not change the sperm quality of men with grade IV or V varicocele. The placebo was inactive, and there were no side-effects of active treatment. Cinnoxicam is a safe and reliable therapeutic option for men with oligoasthenospermia associated with a grade III varicocele, but surgery is better for those with grade II, IV and V.
Article
Adult varicocele presents a challenge for male reproductive specialists. We have yet to fully elucidate the pathophysiology of varicocele. The enigma of the varicocele, although a source of frustration for clinicians, has been a siren call for researchers as attested to by the substantial, if flawed body of literature on the topic. We critically review recent publications on varicocele. Although yielding mixed results, studies this year have explored the potential relationship between oxidative stress and varicocele-associated infertility. In clinically focused research, one group tackled the contentious question of efficacy of surgical varicocele management. Building on the errors of prior meta-analyses, this study takes a fresh view on an old but vital topic. Finally, it is becoming clearer that varicocele affects Leydig cell function as well as seminiferous tubular function, and is a risk factor for androgen deficiency. With exceptions, recent studies support a role for varicocelectomy in the management of infertile couples. In addition, evidence is accumulating that early repair of varicoceles, especially large varicoceles, may be effective in preventing future infertility and may be an effective treatment for androgen deficiency.
Article
To assess the evidence for or against horse-chestnut seed extract (HCSE) as a symptomatic treatment of chronic venous insufficiency (CVI). Computerized literature searches were performed in MEDLINE, EMBASE, BIOSIS, CISCOM, and the Cochrane Library (all from their respective institution to December 1996). The search terms were "horse chestnut," "Aesculus hippocastanum," "escin," and "Rosskastanie" (German for "horse chestnut"). There were no restrictions on the language of publication. Double-blind, randomized controlled trials of oral HCSE for patients with CVI were included. Identifiers were removed from all publications before assessment. Data were extracted in a standardized, predefined manner. Trial outcomes and the methodological quality of each trial were independently assessed by the 2 reviewers. The superiority of HCSE is suggested by all placebo-controlled studies. The use of HCSE is associated with a decrease of the lower-leg volume and a reduction in leg circumference at the calf and ankle. Symptoms such as leg pain, pruritus, and a feeling of fatigue and tenseness are reduced. Five comparative trials against the reference medication indicate that HCSE and O-(beta-hydroxyethyl)-rutosides are equally effective. One trial suggests a therapeutic equivalence of HCSE and compression therapy. Adverse effects are usually mild and infrequent. These data imply that HCSE is superior to placebo and as effective as reference medications in alleviating the objective signs and subjective symptoms of CVI. Thus, HCSE represents a treatment option for CVI that is worth considering.
Article
Escin, hydroxyethylrutoside (HR), and Daflon have been shown to be safe and effective for the treatment of chronic venous insufficiency (CVI). They seem to work differently than compression therapy, suggesting that they would usefully augment this therapy. All three phlebotonics attenuate the drop in adenosine triphosphate in venous endothelial cells during hypoxia. This attenuates (1) the inflammation response, (2) the attraction of neutrophils, (3) damage to the veins, and (4) the release of growth factors. These factors otherwise would perpetuate venous insufficiency and contribute to varicose veins. Additional independent effects that would be useful for the treatment of CVI are that they reduce permeability and fragility; HR, Daflon, and perhaps escin increase venous tone; escin inhibits hyaluronidase; Daflon and probably HR are attracted to the veins. With regard to similarity, no differences in effect have been established among these phlebotonics.
Article
Varicoceles are vascular lesions of the pampiniform plexus and are the most common identifiable abnormality found in men being evaluated for infertility. Despite the long history associated with varicoceles, there remains much controversy regarding their diagnosis and management. The purpose of this manuscript is to address three of the most pressing controversies: (i) the association of varicoceles with male infertility, (ii) whether varicoceles exert a progressive deleterious effect and (iii) the relationship of varicocele size and outcome following varicocele repair. The current literature is reviewed in an effort to answer these questions. Based upon this analysis, conclusions can be drawn regarding the best management of varicoceles in subfertile men, adolescents, young fertile men and men with subclinical varicoceles. Although there remain many controversies due to a paucity of data, there appears to be a significant difference between adults and adolescents with respect to a progressive deterioration of semen parameters and it is clear that subclinical varicoceles do not play a major role in male infertility.
Article
Aescin, the major active principle from Aesculus hippocastanum (Hippocastanaceae) the horse chestnut tree, has shown satisfactory evidence for a clinically significant activity in chronic venous insufficiency (CVI), haemorrhoids and post-operative oedema. In one controlled trial aescin was shown to be as effective as compression therapy as an alternative to medical treatment for CVI. The therapeutic benefit is well supported by a number of experimental investigations in different animal models, indicative of clearcut anti-oedematous, anti-inflammatory and venotonic properties, mainly related to the molecular mechanism of the agent, allowing improved entry of ions into channels, thus raising venous tension in both in vitro and in vivo conditions. Other mechanisms, i.e. release of PGF(2) from veins, antagonism to 5-HT and histamine, reduced catabolism of tissue mucopolysaccharides, further underline the wide ranging mechanisms of the therapeutic activity of aescin. The excellent tolerability of aescin in the clinic indicates this treatment is of definite clinical benefit in patients with clinical conditions resulting in CVI, haemorrhoids or peripheral oedema formation.
Article
Varicoceles are found in 19 to 41% of infertile men, and is one treatable form of male infertility. The mechanism by which varicoceles cause the variable effect on male infertility and spermatogenesis is still unknown. Experimental animal models play a useful (but limited) role due to the sudden and variable iatrogenic nature of the varicoceles and the duration of the studies. Much of the human data are derived by the characterization of associated differences in measurable parameters between men with and without varicoceles. The role of hyperthermia, testicular blood flow and venous pressure changes, reflux of renal/adrenal products, hormonal dysfunction, autoimmunity, defects in acrosome reaction, and oxidative stress, in the pathophysiology of varicocele will be discussed.
Article
Varicoceles are a common cause of male infertility, but despite data being obtained from animal models and human studies the pathophysiology remains unclear. Recently, molecular and genetic information has been reported on men with varicoceles which may shed new light onto the causes of decreased semen parameters and poor sperm function. Here, a number of studies are reviewed in an attempt to develop a working hypothesis for the relationship of varicoceles and infertility. New studies on testicular tissue of men with varicoceles have demonstrated increased apoptosis among developing germ cells, which may be the cause of oligospermia. Other studies with semen have shown increased levels of reactive oxygen species (ROS) in association with poor sperm motility. Recent studies of morphologically abnormal spermatozoa have demonstrated disruption of the sperm head actin by cadmium, a cation reported to be present in high concentrations among some men with varicoceles. Finally, microdeletions of the alpha-1 subunit of the sperm calcium channels in a proportion of men with varicoceles suggests a genetic defect leading to abnormal acrosomal function. The intent of this review was to explain the pathophysiology of varicoceles, and the findings seem to support a 'co-factor' hypothesis. In order for varicoceles to be associated with infertility, they exist as 'co-factors' along with other molecular/genetic problems.
Article
The objective of this study was to detect a therapy for idiopathic and varicocele-associated oligoasthenospermia (OAT). Idiopathic and varicocele OAT patients were randomized into 3 groups. Each group was composed of varying degrees of left varicoceles (graded into 5 grades with echo-color Doppler) and of idiopathic OATs. Group 1 used a placebo, group 2 used oral L-carnitine (2 g/d) + acetyl-L-carnitine (1 g/d), group 3 used L-carnitine/acetyl-L-carnitine + 1 x 30-mg cinnoxicam suppository every 4 days. Drugs were administered for 6 months. The groups were composed as follows: group 1, 71 varicoceles and 47 idiopathic OATs; group 2, 62 varicoceles and 39 idiopathic OATs; group 3, 62 varicoceles and 44 idiopathic OATs. Sperm concentration, motility, and morphology before during and after treatments were assessed. Pregnancy rates and side effects were recorded. Group 1 did not have modified sperm patterns during treatment. Group 2 had significantly increased sperm patterns at 3 and 6 months into therapy in idiopathic patients and in patients with grades I, II, and III varicocele, but not in grades IV and V. Group 3 had significantly increased sperm parameters in all patients, with the exception of grade V varicocele. Group 3 sperm patterns proved significantly higher during therapy than group 2. All sperm patterns fell to baseline after therapy suspension. Minor side effects occurred. Pregnancy rates were 1.7% (group 1), 21.8% (group 2), and 38.0% (group 3) (P <.01). L-carnitine/acetyl-L-carnitine + cinnoxicam suppositories proved a reliable treatment for low-grade varicoceles and idiopathic OATs.
Article
Varicocele is a condition of varicosity and tortuosity of the pampiniform plexus that is often associated with a reduction in the volume of the affected testicle. Today there is much debate about how much the varicocele actually damages the reproductive system and the mechanism through which this occurs. Furthermore, it has not yet clearly been established if treatment is truly useful to restore testicular function. The goal of this study was to evaluate changes in the volume of the affected testis after treatment and to examine any correlations between volume and seminal parameters. We evaluated 43 patients with left idiopathic varicocele with ultrasound scan of the testis before and after surgery; testicular volume was obtained using the ellipsoid formula. We also examined semen parameters before and at an average time of 1 year after the procedure, using the WHO indications. We performed 2 statistical analyses, comparing changes in testicular volume before and after surgery, and volume with seminal parameters. Statistical analysis shows a significant increase of testicular volume after varicocele treatment (P < .05). Furthermore, the total number of spermatozoa and fast progressive spermatozoa rates significantly increased after surgery (respectively P < .05 and P < .01) (Figure 1). The Spearman correlation coefficient shows a good relationship between testicular volume and total number of spermatozoa (r = .445; P = .01). Our data point to the possibility that the affected testicle could benefit in terms of trophism and function after varicocele treatment. Ultrasound scan at follow-up permits assessment of not only the presence of recurrence, but it is also useful for evaluating trophism.
Article
Oxidative stress results from the production of oxygen radicals in excess of the antioxidant capacity of the stressed tissue. Many conditions or events associated with male infertility are inducers of oxidative stress. X-irradiation, for example, or exposure to environmental toxicants and the physical conditions of varicocele and cryptorchidism have been demonstrated to increase testicular oxidative stress, which leads to an increase in germ cell apoptosis and subsequent hypospermatogenesis. Such stress conditions can cause changes in the dynamics of testicular microvascular blood flow, endocrine signaling, and germ cell apoptosis. Testicular oxidative stress appears to be a common feature in much of what underlies male infertility, which suggests that there may be benefits to developing better antioxidant therapies for relevant cases of hypospermatogenesis.
Klinischer Untersuchung von Aescin-Ampullen bei postoperativen und posttraumatischen Oedemen
  • Hefti
Hefti, F., Kappeler, U., 1975. Klinischer Untersuchung von Aescin-Ampullen bei postoperativen und posttraumatischen Oedemen. Schweiz. Rundsch. Med. Praxis 64, 73–77.
Traitement pr eventif et curatif des oed emes en pathologie chirurgicale par le R eparil intraveineux
  • R Devin
  • A Branchereau
  • M C Bourgoin
Devin, R., Branchereau, A., Bourgoin, M.C., 1976. Traitement pr eventif et curatif des oed emes en pathologie chirurgicale par le R eparil intraveineux. Mediterr. Med. 94, 105–109.
L’azione della escina nell’edema post-operatorio
  • Gualtieri
Gualtieri, L., 1978. L'azione della escina nell'edema post-operatorio. Gazz. Med. Ital. 137, 339–344.
Traitement préventif et curatif des oedémes en pathologie chirurgicale par le Réparil intraveineux
  • Devin
Etude en double aveugle du Reparil en Proctologie
  • Pirard
Tratement préventif et curatif de l’oedème post-opératoire en chirurgie plastique par le 1323 AN
  • Mouly
Behandlung postoperativer Oedeme mit Reparil
  • Otto