A Randomized Double-blind Placebo-controlled Trial to Assess the Effect of Tamarind seed in Premature Ejaculation
Abdulla Homayuonfar1, Alireza Aminsharifi2, Alireza Salehi1, Ali Sahraian3, Shadab Dehshari4, Mohsen Bahrami5
1 School of Traditional Medicine, Research Center for Traditional Medicine and History of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
2 Department of Urology, Shahid Faghihi Hospital, Shiraz University of Medical Sciences, Shiraz, Iran
3 Research Center for Psychiatry and Behavioral Sciences, Shiraz University of Medical Sciences, Shiraz, Iran
4 Department of Pharmacognosy, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
5 Department of Traditional Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
|Date of Web Publication||24-Apr-2018|
Dr. Abdulla Homayuonfar
School of Traditional Medicine, Research Center for Traditional Medicine and History of Medicine, Shiraz University of Medical Sciences, Shiraz
Source of Support: None, Conflict of Interest: None
Background: This randomized clinical trial was aimed to evaluate the effect of oral use of tamarind seed powder as an herbal product in patients affected by premature ejaculation (PE). Materials and Methods: In this study, 75 patients randomized in tamarind group (25 patients received daily 130 mg tamarind seed powder), paroxetine group (25 patients received daily 20 mg paroxetine), and placebo group (25 patients). Patients received the treatment regimen for 4 weeks. The primary outcome was intravaginal ejaculatory latency time (IELT). The secondary outcomes were PE diagnostic tool score, sexual function using International Index of Erectile Function (IIEF), and complications. Studied sexual functions include erectile function, orgasmic function, sexual desire, intercourse satisfaction, and overall satisfaction. Results: The mean of IELT in tamarind, paroxetine, and placebo groups at baseline was 35.2 ± 26.5, 38 ± 27.6, and 44 ± 34.9 s and at the end of study was 49.5 ± 48.2, 147.4 ± 209.6, and 46.9 ± 37.6 s, respectively, which in paroxetine group significantly increased compared to other groups. IIEF scores for orgasmic function and intercourse satisfaction for paroxetine after treatment significantly increased than that of other groups. The differences between tamarind and placebo groups for studied variables were not statistically significant. The mean of increases in IELT for tamarind, paroxetine, and placebo groups was 14.35 ± 34.3, 109.4 ± 213.4, and 2.9 ± 9.3 s, respectively, which in paroxetine group was significantly higher than other groups and in tamarind group was significantly higher than placebo. Conclusions: Paroxetine was significantly better than tamarind seed powder and placebo although side effect in paroxetine was more frequent. IELT significantly more increased in tamarind group compared to placebo.
Keywords: Complementary medicine, paroxetine, premature ejaculation, tamarind seed, Tamarindus indica
|How to cite this article:|
Homayuonfar A, Aminsharifi A, Salehi A, Sahraian A, Dehshari S, Bahrami M. A Randomized Double-blind Placebo-controlled Trial to Assess the Effect of Tamarind seed in Premature Ejaculation. Adv Biomed Res 2018;7:59
|How to cite this URL:|
Homayuonfar A, Aminsharifi A, Salehi A, Sahraian A, Dehshari S, Bahrami M. A Randomized Double-blind Placebo-controlled Trial to Assess the Effect of Tamarind seed in Premature Ejaculation. Adv Biomed Res [serial online] 2018 [cited 2019 Apr 21];7:59. Available from: http://www.advbiores.net/text.asp?2018/7/1/59/230869
| Introduction|| |
Sexual dysfunction is a common condition affecting both men and women and preventing them from experiencing satisfaction from the sexual activity. Erectile dysfunction and premature ejaculation (PE) are the main and prevalent sexual complaints among men., PE as the most prevalent sexual problem in men is defined as persistent ejaculation with minimal sexual stimulation before or soon after penetration, on which the individual has minimal voluntary control over. The history of PE is probably as old as human history, and was mentioned in medieval Persia as well as other antiquity and the medieval period. Epidemiologic studies estimated the prevalence of PE ranging from 10% up to 40%.,, Low self-esteem, interpersonal difficulty, and mental health problems can be caused by PE that can affect both the male and female partner.,
The etiology of PE has not still been fully defined, but it is believed that this condition is multifactorial, and associations with psychological, environmental, endocrine, and neurobiological factors have been made. Therefore, treatments of PE may include both behavioral and/or pharmacological interventions.,,,,,,,,,,
A number of drugs with varying degrees of success have been used treating PE. Antidepressants, local anesthetic agents, and phosphodiesterase type 5 inhibitors are currently used by clinicians for the management of PE. At present, fluoxetine, sertraline, paroxetine, and citalopram are common selective serotonin reuptake inhibitors used in the treatment of PE. Dapoxetine is the only approved oral drug to treat PE but it is expensive and is not available in many countries. The ideal treatment for PE would be a novel medication with rapid-acting properties which is effective without sexual or systemic side effects.
In the recent years, in many countries, the use of various methods of alternative medicine has increased. Various herbal products in traditional and alternative medicine have been prepared for men and women seeking improvement in their sexual life. In some previous studies,,,,,, a variety of herbal products were assessed in patients suffering from PE, and different and limited findings reported for these surveys and the efficacy of most herbal agents in treating sexual problems remain uncertain.
Tamarindus indica is a medicinal plant with high antioxidant activities. Different parts of the plant are used in food products, industries, and medicine. Some previous studies reported the effects of tamarind seed in medical practice for some purposes.,,,, In Iranian traditional medicine, tamarind seed powder was recommended for the management of PE, but there is no evidence-based information for its efficacy. In the present study, we assess the possible therapeutic role of tamarind seed powder in patients affected by PE through a randomized controlled trial.
| Materials and Methods|| |
This randomized, double-blind controlled trial was conducted between March and December 2015, on 75 male patients with PE who referred to urology clinics in Shiraz, Iran. The Ethics Committee of Shiraz University of Medical Sciences approved this study; also, this study is registered at the Iranian Registry of Clinical Trials [IRCT2015051422281N1]. All patients were informed about the procedure of the survey and written informed consent was obtained from all of them. PE was diagnosed by allocating the International Society for Sexual Medicine guideline. Patients were eligible if their ejaculation, always or nearly always, occurs prior to or within about 2 min of vaginal penetration. Other inclusion criteria were age between 20 and 50 years, being married and in a stable sexual relationship with a female partner for at least 6 months, having sexual intercourse once a week or more often and the Premature Ejaculation Diagnostic Tool (PEDT) score >8. The exclusion criteria were a history of psychiatric disorders requiring therapy/medication, diabetes mellitus, renal insufficiency, liver diseases, dyslipidemia, hypertension, hypothyroidism or hyperthyroidism, cardiac arrhythmias, other sexual dysfunctions, and sexual dysfunction in the partner. In addition, men who have been taking medications that could have affected their ejaculatory function were excluded.
Eligible patients were randomly divided into three 25-member groups, using random-maker software “Random Allocation” (Isfahan, Iran). Patients in tamarind group received 130 mg of tamarind seed powder and 260 mg of sugar one time per day. Patients in paroxetine group received one time per day of 20 mg of paroxetine. Control group included 25 patients who received one time per day placebo. To prepare the tamarind seed powder, first, the seeds were separated from the shell and then changed it into powder. The whole seed powder should pass 80-mesh screens. Hence, the seed powder was mixed with 2-fold of sugar, and for each capsule of tamarind, 380 mg of mixture was used. Dose of tamarind seed powder in this study was the lowest recommended dose in Iranian traditional medicine. All treatments were taken for 4 weeks and patients were instructed to have twice weekly vaginal sexual intercourse during treatments and were not permitted to use condoms or topical anesthetics. To maintain blinding, patients and nurses were unaware of the treatment allocation and all drugs used in the study were prepared in the same capsules and were formally manufactured as the same in Faculty of Pharmacy, Shiraz University. Drugs were set in a coded envelops and eligible patients received the content of one of these envelops by random.
Collected data included age, education level, intravaginal ejaculatory latency time (IELT), PE status, sexual function, and complications. IELT was measured to assess the effectiveness of the treatment and was defined as the time between the start of vaginal intromission and the start of intravaginal ejaculation. Patients were asked to measure IELT in any sexual intercourse during 2 weeks before starting medications and the average of these times was set as baseline IELT. PE status was evaluated by PEDT including five questions with a total of 20 score. A PEDT score of 0–8 was considered as not having PE, score of 8–10 as suspect to PE, and scores of 11 and above as having PE. Sexual function was measured with the International Index of Erectile Function (IIEF). IIEF is a brief, self-administered scale that consists of 15 questions assessing five domains of male sexual function:, six items to evaluate erectile function (questions 1–5 and 15), two items to evaluate orgasmic function (questions 9 and 10), two items to evaluate sexual desire (questions 11 and 12), three items to evaluate intercourse satisfaction (questions 6–8), and two items to evaluate overall satisfaction (questions 13 and 14). Higher score of IIEF indicates better sexual functioning. All variables were recorded before and at the end of 4-week treatment period.
The comparison of mean formula for the level of IELT was used to calculate the sample size with α = 0.05 and 80% power, based on values in Falahatkar et al's. study. All statistical analyses were done using SPSS software for Windows (SPSS, Inc., Chicago, IL, USA, version 20). Descriptive data are reported as mean ± standard deviation, median (IQR), or number (percentage). Repeated measurements of ANOVA, ANCOVA, and Chi-square test were used to compare all the studied variables between groups. The mean of differences among the three study groups after treatments compared to baseline for the studied variables was analyzed using one-way ANOVA with Bonferroni test as post hoc tests. The level of significance is considered to be <0.05.
| Results|| |
Of 94 reviewed patients, 19 patients did not enter to the study (15 patients were not eligible and four patients refused informed consent). Seventy-five patients were eligible and randomly assigned into three intervention groups. Patients were followed up for 4 weeks and during follow-up three patients did not desire to continue and excluded. Finally, 72 patients with a mean age of 36.7 ± 6.6 years (in placebo, paroxetine, and tamarind, 24, 23, and 25 patients, respectively) completed the study and their data were analyzed [Figure 1]; the mean of age was not significantly different between the three groups.
|Figure 1: Flowchart depicts patients entered to the study who were divided into the study groups and analyzed|
Click here to view
[Table 1] illustrates the mean scores on IELT, PEDT, and IIEF for the three study groups. Results from repeated measurements of ANOVA with Bonferroni test as post hoc analyses showed that the mean of IELT, IIEF orgasmic function, and IIEF intercourse satisfaction scores in paroxetine group after treatment significantly increased than that of the other groups. The mean of IIEF sexual desire and IIEF total scores in paroxetine group after treatment significantly increased compared to placebo group. The mean of PEDT, IIEF overall satisfaction, and IIEF erectile function scores was not significantly different among the study groups. Between tamarind and placebo groups, there was no significant difference for all studied variables. Furthermore, as shown in this table, after ANOVA analysis and controlling the effect of baseline values as covariates, after treatment, only IIEF sexual desire score was not significantly different among the three groups but all other studied variables were significantly different among the study groups.
|Table 1: Intravaginal ejaculation latency time, premature ejaculation diagnostic tool, and International Index of Erectile Function Scores before and after study between groups|
Click here to view
[Table 2] shows the comparison of differences among groups after treatments compared to baseline for IELT, PEDT, and IIEF scores. As shown in this table, the mean of increases in paroxetine group was significantly more than that of other groups. In addition, the mean of changes in PEDT, IIEF overall satisfaction, IIEF intercourse satisfaction, and IIEF total scores among the three groups after treatment was statistically significant. The mean of changes in IIEF orgasmic function, IIEF orgasmic function, and IIEF sexual desire scores was not statistically significant. Post hoc analyses showed that the mean of changes between paroxetine with tamarind group and paroxetine with placebo group was statistically significant and between tamarind group and placebo group the mean of changes was not statistically significant.
|Table 2: Mean differences of studied variables after intervention compared to baseline|
Click here to view
Comparison of adverse events occurring among study groups is shown in [Table 3]. As shown in this table, 43% of patients in paroxetine group reported adverse event whereas one patient in tamarind group and one patient in placebo group reported adverse event (P = 0.0002). The most common adverse events were drowsiness and nausea which were prevalent in paroxetine group than that of other groups. The frequency of constipation and reduced libido was not significantly different among the three groups.
| Discussion|| |
PE is a common condition affecting personal distress which may in turn affect the relationship of the man with his partner. Nearly, one out of five men in the world suffers from PE. For many decades, the quest for an effective tablet to the treatment of PE has been increased. However, limited understood about the pathophysiology of PE, the clinician has faced a real challenge to treat PE. A number of drugs with varying degrees of success have shown in treating PE. But, at the present time, dapoxetine is the only licensed drug in the treatment of PE only in some countries. Dapoxetine is not available in many countries and also the cost of the drug is high, so there is a search of new option in the medical management of PE, especially in developing and middle-income countries. In the recent years, in many countries, the use of various methods of alternative medicine has increased. Various surveys on traditional and alternative medicine have highlighted the widespread use of herbal products. And, around the world, these have become an important and indispensable part of public health care. In this randomized study, we evaluated the effect of tamarind seed powder on PE compared to paroxetine and placebo. Findings revealed that no significant difference was detected in the end points between tamarind seed powder and placebo. Paroxetine was significantly better than tamarind seed powder to improve IELT in PE patients but side effect in paroxetine group was significantly more frequent than that of tamarind group. The dose of tamarind seed powder used in our study is the lowest recommended dose in traditional medicine texts and it can be used in higher dose. So, higher dose can be assessing in further clinical trials.
To the best of our knowledge, the present study is the first to assess the effect of tamarind seed powder on PE. Of note, after 4 weeks' use of tamarind, although there was no difference between tamarind and placebo groups, the average of increase in IELT in tamarind group was more than placebo group (14.9 vs. 2.9, respectively) and all other studied variables were improved compared to placebo group. It is possible that low sample size decreases the power of our study to detect differences between groups. Also, in Iranian traditional medicine, tamarind seed powder was suggested for PE with no exact recommended dosage or time for its use. Hence, in the present study, we used tamarind seed powder at small dosage during 4 weeks and increase in dosage and time may be more effective than placebo on this outcome.
Four weeks' use of paroxetine in our study similar to other studies ,, shows improvements in IELT sexual satisfaction and other outcomes with more side effects than control group. A systematic review short report shows that a range of treatment options are available for patients presenting with PE. Pharmacological interventions, topical anesthetics, and behavioral therapies are useful approaches to PE management, but pharmacological and topical therapies are associated with some adverse effects. Furthermore, there is limited evidence regarding the long-term safety and effectiveness of treatments and following cessation of many treatments their effects may be expected to end. On the other hand, other therapies including acupuncture, yoga, Chinese medicine, and herbal medicine were assessed in other studies as alternative medicine in the management of PE.,,,,,,,, However, because of verity and limited evidence-based information, the efficacy and safety of these approaches compared to placebo or other usual treatments are unclear. In the present study, for the first time, based on Iranian traditional medicine recommendation, small dose of tamarind seed powder as an alternative treatment to PE management was assessed and our findings were not different from placebo and were significantly less effective than paroxetine. However, as a new herbal product approach, additional research is required to eventually assess different doses and periodic use of tamarind seed powder alone or combined with other treatments options for the management of PE.
| Conclusions|| |
In conclusion, our study suggested that tamarind seed powder was not significantly different from placebo in the treatment of PE and also paroxetine as a routine treatment was better than tamarind seed powder. This randomized study is exploratory with no reported side effect for tamarind compared to paroxetine. So, the future researches can be design on higher dose of tamarind seed powder on a large number of patients with PE.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Rosen RC. Prevalence and risk factors of sexual dysfunction in men and women. Curr Psychiatry Rep 2000;2:189-95.
Hatzimouratidis K, Amar E, Eardley I, Giuliano F, Hatzichristou D, Montorsi F, et al.
Guidelines on male sexual dysfunction: Erectile dysfunction and premature ejaculation. Eur Urol 2010;57:804-14.
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th
ed. Text Revision. (DSM-IVTR). Washington, DC: American Psychiatric Association; 2000. p. 554.
Sharifi AR, Homayounfar A, Mosavat SH, Heydari M, Naseri M. Premature ejaculation and its remedies in Medieval Persia. Urology 2016;90:225-8.
Porst H, Montorsi F, Rosen RC, Gaynor L, Grupe S, Alexander J. The Premature Ejaculation Prevalence and Attitudes (PEPA) Survey: Prevalence, comorbidities, and professional help-seeking. Eur Urol 2007;51:816-24.
Giuliano F, Patrick DL, Porst H, La Pera G, Kokoszka A, Merchant S, et al.
Premature ejaculation: Results from a five-country European observational study. Eur Urol 2008;53:1048-57.
Patrick DL, Althof SE, Pryor JL, Rosen R, Rowland DL, Ho KF, et al.
Premature ejaculation: An observational study of men and their partners. J Sex Med 2005;2:358-67.
McMahon CG, Althof S, Waldinger MD, Porst H, Dean J, Sharlip I, et al.
An evidence-based definition of lifelong premature ejaculation: Report of the international Society for Sexual Medicine ad Hoc Committee for the Definition of Premature Ejaculation. BJU Int 2008;102:338-50.
Porst H, Montorsi F, Rosen RC, Gaynor L, Grupe S, Alexander J, et al.
The Premature Ejaculation Prevalence and Attitudes (PEPA) survey: Prevalence, comorbidities, and professional help-seeking. Eur Urol 2007;51:816-23.
McMahon CG, Abdo C, Incrocci L, Perelman M, Rowland D, Waldinger M, et al.
Disorders of orgasm and ejaculation in men. J Sex Med 2004;1:58-65.
Hyun JS, Kam SC, Kwon OY. Changes of cerebral current source by audiovisual erotic stimuli in premature ejaculation patients. J Sex Med 2008;5:1474-81.
Cooper K, Martyn-St James M, Kaltenthaler E, Dickinson K, Cantrell A. Interventions to treat premature ejaculation: A systematic review short report. Health Technol Assess 2015;19:1-180, v-vi.
Xin ZC, Zhu YC, Yuan YM, Cui WS, Jin Z, Li WR, et al.
Current therapeutic strategies for premature ejaculation and future perspectives. Asian J Androl 2011;13:550-7.
Mohee A, Eardley I. Medical therapy for premature ejaculation. Ther Adv Urol 2011;3:211-22.
Rowland D, Tai W. A review of plant-derived and herbal approaches to the treatment of sexual dysfunctions. J Sex Marital Ther 2003;29:185-205.
Thomas CA, Tyagi S, Yoshimura N, Chancellor MB, Tyagi P. Effect of hyperforin-enriched extract on pro-ejaculatory effect of 8-hydroxy-2-(di-N-propylamino) tetralin in anesthetized rats. Urology 2007;70:813-6.
Ratnasooriya WD, Fernando TS. Effect of black tea brew of camellia sinensis on sexual competence of male rats. J Ethnopharmacol 2008;118:373-7.
Zavatti M, Zanoli P, Benelli A, Rivasi M, Baraldi C, Baraldi M, et al.
Experimental study on Satureja montana
as a treatment for premature ejaculation. J Ethnopharmacol 2011;133:629-33.
Kenjale R, Shah R, Sathaye S. Effects of Chlorophytum borivilianum
on sexual behaviour and sperm count in male rats. Phytother Res 2008;22:796-801.
Song GH, Halmurat U, Geng JC, Feng LC, Yilihamujiang S, Ma C, et al
. Clinical study on the treatment of premature ejaculation by Uighur medicine gu-jing-mai-si-ha tablet. Chin J Integr Med 2007;13:185-9.
Choi YD, Park CW, Jang J, Kim SH, Jeon HY, Kim WG, et al.
Effects of Korean ginseng berry extract on sexual function in men with erectile dysfunction: A multicenter, placebo-controlled, double-blind clinical study. Int J Impot Res 2013;25:45-50.
De Caluwé E, Halamová K, Van Damme P. Tamarindus indica
L.: A review of traditional uses, phytochemistry and pharmacology. Afr Focus 2010;23:53-83.
Vargas-Olvera CY, Sánchez-González DJ, Solano JD, Aguilar-Alonso FA, Montalvo-Muñoz F, Martínez-Martínez CM, et al.
Characterization of N-diethylnitrosamine-initiated and ferric nitrilotriacetate-promoted renal cell carcinoma experimental model and effect of a tamarind seed extract against acute nephrotoxicity and carcinogenesis. Mol Cell Biochem 2012;369:105-17.
Aravind SR, Joseph MM, Varghese S, Balaram P, Sreelekha TT. Antitumor and immunopotentiating activity of polysaccharide PST001 isolated from the seed kernel of Tamarindus indica
: An in vivo
study in mice. ScientificWorldJournal 2012;2012:361382.
Sole SS, Srinivasan BP, Akarte AS. Anti-inflammatory action of tamarind seeds reduces hyperglycemic excursion by repressing pancreatic β-cell damage and normalizing SREBP-1c concentration. Pharm Biol 2013;51:350-60.
Shahraki MR, Harati M, Shahraki AR. Prevention of high fructose-induced metabolic syndrome in male Wistar rats by aqueous extract of Tamarindus indica
seed. Acta Med Iran 2011;49:277-83.
Maiti R, Das UK, Ghosh D. Attenuation of hyperglycemia and hyperlipidemia in streptozotocin-induced diabetic rats by aqueous extract of seed of Tamarindus indica
. Biol Pharm Bull 2005;28:1172-6.
Althof SE, Abdo CH, Dean J, Hackett G, McCabe M, McMahon CG, et al.
International society for sexual medicine's guidelines for the diagnosis and treatment of premature ejaculation. J Sex Med 2010;7:2947-69.
Pakpour AH, Yekaninejad MS, Nikoobakht MR, Burri A, Fridlund B. Psychometric properties of the Iranian version of the premature ejaculation diagnostic tool. Sex Med 2014;2:31-40.
Rosen RC, Riley A, Wagner G, Osterloh IH, Kirkpatrick J, Mishra A, et al.
The International Index of Erectile Function (IIEF): A multidimensional scale for assessment of erectile dysfunction. Urology 1997;49:822-30.
Pakpour AH, Zeidi IM, Yekaninejad MS, Burri A. Validation of a translated and culturally adapted Iranian version of the international index of erectile function. J Sex Marital Ther 2014;40:541-51.
Falahatkar S, Asgari A, Hosseini Sharifi SH, Joafshani MA, Emadi SA, Khaledi F. Efficacy and safety of herbal drug, Hypericum perforatum
in the treatment of premature ejaculation. J Guilan Univ Med Sci 2009;18:53-8.
Waldinger MD, Hengeveld MW, Zwinderman AH. Paroxetine treatment of premature ejaculation: A double-blind, randomized, placebo-controlled study. Am J Psychiatry 1994;151:1377-9.
Salonia A, Rocchini L, Sacca' A, Pellucchi F, Ferrari M, Carro UD, et al.
Acceptance of and discontinuation rate from paroxetine treatment in patients with lifelong premature ejaculation. J Sex Med 2009;6:2868-77.
Alghobary M, El-Bayoumy Y, Mostafa Y, Mahmoud el-HM, Amr M. Evaluation of tramadol on demand vs. Daily paroxetine as a long-term treatment of lifelong premature ejaculation. J Sex Med 2010;7:2860-7.
Sunay D, Sunay M, Aydoǧmuş Y, Baǧbancı S, Arslan H, Karabulut A, et al.
Acupuncture versus paroxetine for the treatment of premature ejaculation: A randomized, placebo-controlled clinical trial. Eur Urol 2011;59:765-71.
Sunay D, Sunay M, Aydoǧmuş Y, Baǧbancı S, Arslan H, Karabulut A, et al
. Acupuncture versus paroxetine for the treatment of premature ejaculation: A randomized, placebo-controlled clinical trial. Eur urol 2011;59:765-71.
Mamidi P, Gupta K. Efficacy of certain yogic and naturopathic procedures in premature ejaculation: A pilot study. Int J Yoga 2013;6:118-22.
] [Full text]
[Table 1], [Table 2], [Table 3]