Suspected adverse reactions to medications and food supplements containing Serenoa repens: A worldwide analysis of pharmacovigilance and phytovigilance spontaneous reports.

The safety of Serenoa repens (SR)-containing products was evaluated conducting a retrospective worldwide analysis of pharmaco- and phytovigilance report forms of suspected adverse reactions (SARs) collected up to 31 January 2022. Multivariate logistic regression was performed to estimate the odds ratios (ORs) of serious SAR. A total of 1810 report forms were analysed; 92% of subjects were males, with a median age of 69 years; 44% of cases were defined as serious. Subjects exposed to dietary supplements had a higher risk of developing serious SARs (OR: 1.60 [95% CI: 1.20-2.15]), as subjects exposed to 2-5 (OR: 1. 83 [95% CI: 1.30-2.58]) or more than 5 (OR: 3.45 [95% CI: 2.36-5.06]) suspect/interacting products. The probability of experiencing serious SAR was higher for subjects exposed to concomitant products (OR: 1.55 [95% CI: 1.15-2.08]), to more than four active compounds (OR: 4.38 [95% CI: 3.21-5.99]) and to SR for more than 14 days (OR: 1.89 [95% CI: 1.10-3, 22]), and lower for subjects exposed to higher doses of SR (OR: of 0.34 [95% CI: 0.20-0.58]). This evidence improves awareness on safety of SR containing products, suggesting the need of a further update of periodic reviews by national and international regulatory agencies.

The efficacy and safety of Serenoa repens extract for the treatment of patients with chronic prostatitis/chronic pelvic pain syndrome: a multicenter, randomized, double-blind, placebo-controlled trial.

PURPOSE: To perform a placebo-controlled trial to evaluate the efficacy and safety of Serenoa repens extract (SRE) for the treatment of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). METHODS: We conducted a double-blind, randomized, placebo-controlled, multicenter, clinical phase 4 study of 221 patients with CP/CPPS across 11 centers. Participants were randomly assigned in a 2:1 ratio to receive SRE or placebo for 12 weeks. The primary efficacy endpoint was the change in total score on the National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI). Secondary efficacy endpoints included improvements within each domain of NIH-CPSI, clinical response rate, and International Index of Erectile Function 5 items (IIEF-5). RESULTS: In total, 226 patients were enrolled and randomized between January 2017 and June 2018. Of these 221 patients were included in the intent-to-treat analysis: 148 in the SRE group and 73 patients in the placebo group. Compared to the placebo, SRE led to statistically significant improvements in the NIH-CPSI total score and sub-scores. The significant improvements of NIH-CPSI scores were established after 2 weeks from the first dose, and continued to the end of the treatment. Furthermore, a significantly higher rate of patients achieved a clinical response in the SRE group compared with that in the placebo group (73.0% vs 32.9%, P < 0.0001). Only minor adverse events were observed across the entire study population. CONCLUSIONS: SRE was effective, safe, and clinically superior to placebo for the treatment of CP/CPPS. ChiCTR-IPR-16010196, December 21, 2016 retrospectively registered.

Serenoa repens as an Endocrine Disruptor in a 10-Year-Old Young Girl: A New Case Report.

Serenoa repens, commonly known as saw palmetto, is the sole species currently classified in the genus Serenoa. The plant is a low shrubby palm that is native of West Indies, and it grows in the coastal lands of North America and other European mediterranean countries. Its fruits contain high concentrations of fatty acids and phytosterols. S. repens extracts have been studied for the symptomatic treatment of benign prostatic hyperplasia. Recently, they have been proposed to treat androgenic alopecia and other hair disorders. We report a new case of hot flashes in a 10-year-old girl using a food supplement containing the extract of S. repens for the treatment of hirsutism. When the girl discontinued the treatment, the hot flashes stopped. A 'rechallenge' of the supplement was tried and symptoms reappeared. About 4 months after starting therapy, the girl experienced menarche. Exposure to the plant-derived product could be responsible for the appearance of menarche. In our opinion, use of phytotherapeutic agents in pediatric patients should be associated to a better evaluation of benefit/risk profile taking in account the physiological changes that occurs at different ages in this subgroup of population.

Hot flashes in a young girl: a wake-up call concerning Serenoa repens use in children.

Extracts of the plant Serenoa repens are widely used in male adults for the treatment of benign prostatic hyperplasia. Recently, therapy with S repens has been proposed as a "natural" alternative to conventional treatments for male androgenetic alopecia as well as for other hair disorders. Telogen effluvium is a form of alopecia characterized by abnormality of hair cycling, resulting in excessive loss of telogen hair. We report the case of an 11-year-old girl presenting hot flashes that appeared after treatment of telogen effluvium with a food supplement containing S repens that lasted for ~2 months. When use of the product was discontinued, the hot flashes no longer occurred. Four months after the start of S repens intake and 45 days from the cessation of therapy, the girl experienced menarche at the age of 11 years. The Naranjo adverse drug reaction probability scale indicated a probable relationship (score of 6) between the appearance of hot flashes and the intake of S repens. A correlation between exposure to S repens and the onset of menarche is not certain, but it cannot be excluded. Medicinal products or food supplements containing S repens are generally well tolerated in male adults, but we believe that their use in pediatric patients should be better evaluated.

Dietary supplements for benign prostatic hyperplasia: an overview of systematic reviews.

Benign prostatic hyperplasia (BPH) is a common chronic condition in older men. The aim of this overview of systematic reviews (SRs) is to summarise the current evidence on the efficacy and adverse effects of dietary supplements for treating BPH with lower urinary tract symptoms. We searched 5 electronic databases and relevant overviews without limitations on language or publication status. Six SRs of 195 articles were included in this overview. Serenoa repens was reviewed in 3 studies and no specific effect on BPH symptoms and urinary flow measures was observed. However, ß-sitosterol, Pygeum africannum and Cernilton were reviewed in one study each, and significant improvement was observed for all three. All the included compounds have mild and infrequent adverse effects. SRs on ß-sitosterol, Pygeum africannum and Cernilton have not been updated since 2000, thus an update of reviews on these compounds will be necessary in the future.

Serenoa repens in benign prostatic hypertrophy: analysis of 2 Italian studies.

AIM: Benign prostatic hypertrophy (BPH), which is characterized by a progressive swelling of the prostate causing symptoms of the lower urinary tract, is the second pathology as frequency among the diagnoses placed in men every year in Italy. The extract of Serenoa repens is an alternate therapeutic option to traditional drug therapies with a good profile of efficacy and safety for the management of the symptoms of BPH. The aim of this paper was to analyze systematically the results of two Italian studies carried out on patients with BPH treated with extract of serenoa repens (SABA. a product of Lampugnani Farmaceutici S.p.A.). METHODS: The studies were carried out on a total of 70 adult patients with diagnosis of benign prostatic hypertrophy. In one study the patients were treated with Serenoa repens 320 mg/day for 30 days; in the other study the patients received Serenoa repens 320 mg/day or Pygeum africanum (Tadenan) 4 capsules of 25 mg/day for 30 days. RESULTS: Both studies showed an improvement versus the baseline of about 50% of dysuria and pollakisuria, an about 50% increase in micturition rate with positive effects also in terms of reduction of the micturition rate and of prostate size. Also the tolerability profile was favorable. CONCLUSION: The extract of Serenoa repens (SABA Lampugnani Farmaceutici S.p.A.) administered at the dose of 320 mg/day to patients with benign prostatic hypertrophy, is effective in terms of improvement of the functional symptomatologic picture improvement and of the instrumental parameters with a good tolerability profile.

[Associating Serenoa repens, Urtica dioica and Pinus pinaster. Safety and efficacy in the treatment of lower urinary tract symptoms. Prospective study on 320 patients]. / Associazione di Serenoa repens, Urtica dioica e Pinus pinaster. Sicurezza ed efficacia nel trattamento dei sintomi del basso tratto urinario. Studio prospettico su 320 pazienti.

INTRODUCTION: Serenoa repens (saw palmetto) has been employed for the treatment of lower urinary tract symptoms (LUTS) for several years. Its mechanism of action is believed to be due to antiandrogenic, antiproliferative and antinflammatory properties. An association of Serenoa with the nettle "Urtica dioica" showing antiproliferative activity and the pine "Pinus pinaster" derivative, showing antinflammatory action, has been proposed in recent years. Such an action is hoped to act not only by reducing LUTS but also by preventing the development of prostate cancer. MATERIAL AND METHODS: During the years 2007 and 2008, 320 patients suffering from LUTS were treated with an association of Serenoa repens 320 mg, Urtica dioica 120 mg and Pinus pinaster 5 mg, named IPBTRE. This treatment was administered to all patients for a minimal duration of 30 days to a maximum of a year, either alone or in association with antibiotics or alpha-blockers, if needed. Outcome analysis was based on evaluation of symptoms, prostate volume and maximum flow rate (Qmax). RESULTS: From a careful analysis of the data collected in our database, the following observations can be made: ages varied between 19 and 78 years. The patients were affected by BPH in 46% of cases, chronic prostatitis syndrome in 43%, chronic genital-pelvic pain in 7% and other conditions in 4%, the absolute numbers being 147, 138, 22 and 7 patients, respectively. No untoward side effect was reported in any case. Variations in symptom score could be fully evaluated only in 80 of 320 patients (25%), of whom 68 (85%) reported a significant benefit, with special reference to an improvement of pain, urgency, strangury and nocturia. Data on variations in prostate volume, as measured by digital rectal examination, were available in 84 (26.5%) patients. No significant change was observed. Qmax after treatment was measured in 83 (26%) patients. It did not show significant changes from the initial values. DISCUSSION: The association tested in our study appeared to be safe and well tolerated. No changes in flow rate and prostate volume were observed, but a marked reduction of LUTS was observed in 85% of evaluable cases, especially with regard to pain and irritative symptoms. Whether or not such an association may display a prevention of prostate cancer, may be investigated in additional studies.

Use the INN to avoid confusion between drugs.

Three cases of confusion between brand names have been reported in detail. Previscan (the anticoagulant fluindione) was taken instead of Permixon (saw palmetto extract for prostatic hyperplasia, "serenoa repens") or Preservision (a nutritional supplement for the prevention of age-related eye disease). These medication errors led to sometimes severe haemorrhages.

Serenoa repens (saw palmetto): a systematic review of adverse events.

Serenoa repens (W. Bartram) Small, also known as saw palmetto, is one of the most widely used herbal preparations for the treatment of lower urinary tract symptoms (LUTS) and benign prostatic hyperplasia (BPH). Although a number of randomized controlled trials (RCTs) and systematic reviews of the efficacy of S. repens for the treatment of LUTS and BPH have been published, no systematic review on its drug interactions or adverse events currently exists. This review assesses all available human safety data of S. repens monopreparations. Systematic literature searches were conducted from date of inception to February 2008 in five electronic databases; reference lists and our departmental files were checked for further relevant publications. Information was requested from spontaneous reporting schemes of the WHO and national safety bodies. Twenty-four manufacturers/distributors of S. repens preparations and four herbalist organizations were contacted for additional information. No language restrictions were imposed. Only reports of adverse events in humans from monopreparations of S. repens were included. Data from all articles, regardless of study design, reporting adverse events or interactions were independently extracted by the first author and validated by the second. Forty articles (26 randomized controlled trials, 4 non-randomized controlled trials, 6 uncontrolled trials and 4 case reports/series) were included. They suggest that adverse events associated with the use of S. repens are mild and similar to those with placebo. The most frequently reported adverse events are abdominal pain, diarrhoea, nausea, fatigue, headache, decreased libido and rhinitis. More serious adverse events such as death and cerebral haemorrhage are reported in isolated case reports and data from spontaneous reporting schemes, but causality is questionable. No drug interactions were reported. Currently available data suggest that S. repens is well tolerated by most users and is not associated with serious adverse events. The majority of adverse events are mild, infrequent and reversible, and include abdominal pain, diarrhoea, nausea and fatigue, headache, decreased libido and rhinitis. We found no evidence for drug interactions with S. repens. However, higher quality reporting of adverse events is essential if safety assessments are to be improved in future.

[Serenoa repens in benign prostatic hyperplasia]. / Dvergpalmeekstrakt ved benign prostatahyperplasi.

Serenoa repens is one of many herbal products used to treat benign prostatic hyperplasia. The treatment has been studied extensively, but the methodological quality has often been poor. Metaanalysis of early studies indicate that the treatment may have favourable effects on patients with benign prostatic hyperplasia, but more recent investigations of better methodological quality have questioned these results. The available documentation does not support use of products containing serenoa repens for these patients. Serenoa repens is associated with mild adverse effects comparable to that of placebo.

The effect of herbal medicines on platelet function: an in vivo experiment and review of the literature.

BACKGROUND: Herbal medicines are used by a considerable number of surgical patients. An increased risk of bleeding, substantiated by anecdotal reports, has been attributed to the use of certain herbs, and numerous in vitro experiments have identified some herbal extracts as platelet inhibitors. The purpose of this investigation was to determine whether standard commercial preparations of commonly used herbal medicines have an effect on platelet function in vivo and, by extension, to provide clinical scientific evidence of the safety of their use in the perioperative period. METHODS: Five commercially available herbal agents were investigated, including Ginkgo biloba, garlic, Asian ginseng, St. John's wort, and saw palmetto. In a blinded fashion, one of the agents was administered to 10 adult volunteers at the manufacturer's recommended dose for 2 weeks. At the end of the 2-week period, in vivo platelet function was quantified using the PFA-100 assay. After a 2-week "washout" period, the protocol was repeated using a different agent. This 4-week cycle was repeated for each of the five herbal agents, as well as the control agent aspirin. RESULTS: In vivo platelet function was not affected by the administration of any herbal agent and was markedly inhibited with the administration of aspirin. CONCLUSIONS: The herbal medicines investigated in this study do not affect platelet function in vivo. Neither this experiment nor a review of the literature supports the concern of perioperative bleeding in users of these herbal medicines.

Saw palmetto-induced pancreatitis.

Saw palmetto is a frequently used botanical agent in benign prostatic enlargement (BPH). Although it has been reported to cause cholestatic hepatitis and many medical conditions, Saw palmetto has not been implicated in acute pancreatitis. We report a case of a probable Saw palmetto induced acute hepatitis and pancreatitis. A 55-year-old reformed alcoholic, sober for greater than 15 years, presented with severe non-radiating epigastric pain associated with nausea and vomiting. His only significant comorbidity is BPH for which he intermittently took Saw palmetto for about four years. Physical examination revealed normal vital signs, tender epigastrium without guarding or rebound tenderness. Cullen and Gray Turner signs were negative. Complete blood count and basic metabolic profile were normal. Additional laboratory values include a serum amylase: 2,152 mmol/L, lipase: 39,346 mmol/L, serum triglyceride: 38 mmol/L, AST: 1265, ALT: 1232 and alkaline phosphatase was 185. Abdominal ultrasound and magnetic resonance cholangiography revealed sludge without stones. A hepatic indole diacetic acid scan was negative. Patient responded clinically and biochemically to withdrawal of Saw palmetto. Two similar episodes of improvements followed by recurrence were noted with discontinuations and reinstitution of Saw Palmetto. Simultaneous and sustained response of hepatitis and pancreatitis to Saw palmetto abstinence with reoccurrence on reinstitution strongly favors drug effect. "Natural" medicinal preparations are therefore not necessarily safe and the importance of detailed medication history (including "supplements") cannot be over emphasized.

Saw palmetto for benign prostatic hyperplasia.

BACKGROUND: Saw palmetto is used by over 2 million men in the United States for the treatment of benign prostatic hyperplasia and is commonly recommended as an alternative to drugs approved by the Food and Drug Administration. METHODS: In this double-blind trial, we randomly assigned 225 men over the age of 49 years who had moderate-to-severe symptoms of benign prostatic hyperplasia to one year of treatment with saw palmetto extract (160 mg twice a day) or placebo. The primary outcome measures were changes in the scores on the American Urological Association Symptom Index (AUASI) and the maximal urinary flow rate. Secondary outcome measures included changes in prostate size, residual urinary volume after voiding, quality of life, laboratory values, and the rate of reported adverse effects. RESULTS: There was no significant difference between the saw palmetto and placebo groups in the change in AUASI scores (mean difference, 0.04 point; 95 percent confidence interval, -0.93 to 1.01), maximal urinary flow rate (mean difference, 0.43 ml per minute; 95 percent confidence interval, -0.52 to 1.38), prostate size, residual volume after voiding, quality of life, or serum prostate-specific antigen levels during the one-year study. The incidence of side effects was similar in the two groups. CONCLUSIONS: In this study, saw palmetto did not improve symptoms or objective measures of benign prostatic hyperplasia. (ClinicalTrials.gov number, NCT00037154.).

Tratamientos fitoterápicos para la hipertrofia benigna de próstata: serenoa repens / Phytotherapeutic treatments for benign hypertrophy of prostate: serenoa repens

Serenoa repens es uno de los remedios fitoterápicosmás utilizados en Europa. En Italia y en Alemania es eltratamiento más prescrito para tratar los signos y síntomasderivados de la hipertrofia benigna de próstata.Los meta-análisis y revisiones sistemáticas publicadashasta el momento apuntan a una eficacia similara la de otros tratamientos disponibles en el mercado,como los inhibidores de la 5 α reductasa, (finasteride).La falta de rigor en el diseño de los ensayos clínicoshace imposible obtener resultados concluyentesen cuanto a la eficacia, por lo que se hace necesariocontinuar investigando antes de sustituir el tratamientoconvencional por este remedio fitoterápico

Serenoa repens is one of the most widely used phytotherapeutichome remedies in Europe. In Italy and inGermany is the most prescribed treatment to treat thesigns and symptoms derived from benign hypertrophyof the prostate. Metaanalyses and systematic revisionspublished to date suggest an efficacy similar to that ofother treatments available in the market, such as the 5α reductase (Finasteride): The lack of rigour in the designof the clinical trials makes it impossible to obtainconclusive results with regard to efficacy. This makes itmandatory to do more research before the conventionaltreatment is replaced by this phytotherapeutic method

Evaluation of male sexual function in patients with Lower Urinary Tract Symptoms (LUTS) associated with Benign Prostatic Hyperplasia (BPH) treated with a phytotherapeutic agent (Permixon), Tamsulosin or Finasteride.

OBJECTIVES: Sexual function is one of the aspects in the treatment of lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) that has gained increasing attention. We compared the influence on men's sexuality of Permixon, a lipido-sterolic extract of Serenoa Repens, with Tamsulosin and Finasteride using a specific validated questionnaire exploring patient's sexual functions. METHODS: A database was created comprising patients from 3 main double-blind, randomized studies - Permixon vs. Finasteride, Permixon vs. Tamsulosin and Permixon 160 mg vs. 320 mg including a total of 2511 patients. Three hundred fifty four were on Tamsulosin, 545 on Finasteride and 1612 patients on Permixon. LUTS were assessed using the I-PSS questionnaire. Peak flow rates and prostate volume were recorded. The MSF-4 questionnaire, including 4 items that explore the patient's interest in sex, quality of erection, achievement of orgasm and ejaculation, was used across the studies. This questionnaire was demonstrated as highly reproducible and both psychometrically and clinically valid across different cultures. Correlation coefficients were given to assess the linear relationship between continuous variables. RESULTS: At 3 months, there were no statistically significant differences between the three treatment groups in terms of I-PSS or Qmax evolutions (all p values > 0.05). At 6 months, as compared to pretreatment data, there was a slight increase in sexual disorders in Tamsulosin (+0.3) and Finasteride (+0.8) treated patients while it slightly improved with Permixon therapy (-0.2). Ejaculation disorders were the most frequently reported side effects after Tamsulosin or Finasteride (both +0.2 on the specific MSF-4 question 4). There was no correlation between the evolution of the MSF-4 scores and the evolution in I-PSS neither in patients treated with Permixon, Finasteride or Tamsulosin. However, there was a slight correlation between the MSF-4 score at baseline and the I-PSS at baseline (r2 = 0.032). Although there was a correlation between the MSF-4 and age at baseline (r2 = 0.1452), there was no correlation between the evolution in MSF-4 during therapy and the age of the patients. CONCLUSION: The present study demonstrates that Permixon therapy has no negative impact on male sexual function. Both Finasteride and Tamsulosin had a slight impact on sexual function, especially on ejaculation, although these effects were rare and in line with previous reports about these two drugs.

Use of an embedded N-of-1 trial to improve adherence and increase information from a clinical study.

Withdrawal of participants from randomized trials can occur because of symptoms thought to be related to the study medicine, but the causal relationship between the study medicine and the symptoms is often unclear. Single-patient trials ("N-of-1 trials"), developed to identify optimal therapy for an individual patient in the clinical setting, may provide a means of resolving some of these dilemmas. We describe here the use of an N-of-1 study embedded within a placebo-controlled trial of saw palmetto for a participant who considered withdrawing because he believed the study medication caused an increase in his blood pressure. In this case, the N-of-1 study not only reassured the patient, who decided to remain in the study, but provided potentially useful new information regarding the study medication. Wider use of formal N-of-1 studies may be a valuable tool for improving adherence and determining whether observed side effects are caused by study medication in clinical trials.

The risk-benefit profile of commonly used herbal therapies: Ginkgo, St. John's Wort, Ginseng, Echinacea, Saw Palmetto, and Kava.

Because use of herbal remedies is increasing, a risk-benefit profile of commonly used herbs is needed. This article provides a clinically oriented overview of the efficacy and safety of ginkgo, St. John's wort, ginseng, echinacea, saw palmetto, and kava. Wherever possible, assessments are based on systematic reviews of randomized clinical trials. Encouraging data support the efficacy of some of these popular herbal medicinal products, and the potential for doing good seems greater than that for doing harm. The published evidence suggests that ginkgo is of questionable use for memory loss and tinnitus but has some effect on dementia and intermittent claudication. St. John's wort is efficacious for mild to moderate depression, but serious concerns exist about its interactions with several conventional drugs. Well-conducted clinical trials do not support the efficacy of ginseng to treat any condition. Echinacea may be helpful in the treatment or prevention of upper respiratory tract infections, but trial data are not fully convincing. Saw palmetto has been shown in short-term trials to be efficacious in reducing the symptoms of benign prostatic hyperplasia. Kava is an efficacious short-term treatment for anxiety. None of these herbal medicines is free of adverse effects. Because the evidence is incomplete, risk-benefit assessments are not completely reliable, and much knowledge is still lacking.

Long-term clinical and biologic effects of the lipidosterolic extract of Serenoa repens in patients with symptomatic benign prostatic hyperplasia.

Permixon, the lipidosterolic extract of Serenoa repens, is widely used for the treatment of symptoms associated with benign prostatic hyperplasia (BPH). This open study assessed the efficacy and tolerability of Permixon 160 mg twice daily administered for 2 years. One hundred fifty-five men with clinically diagnosed BPH and complaints of prostatic symptoms were enrolled in the study. At 6, 12, 18, and 24 months, the International Prostate Symptom Score (I-PSS), quality of life, and sexual function score were recorded, and urodynamics and biologic values were measured. Adverse events were recorded every 3 months. I-PSS and quality of life improved significantly from baseline at each evaluation time point. At the end of the study and at each evaluation, maximum urinary flow also improved significantly. Prostate size decreased. Sexual function remained stable during the first year of treatment and significantly improved (P = .001) during the second year. Prostate-specific antigen was not affected, and no changes in plasma hormone levels were observed. Nine patients reported 10 adverse events, none related to treatment. Improvements in efficacy parameters began at 6 months and were maintained up to 24 months. These data demonstrate the long-term efficacy and tolerability of Permixon and support its use as a first-line medical therapy for uncomplicated symptomatic BPH.