Document Type : Randomized Clinical Trials (RCT)


1 School of Biology, Damghan University, Damghan, Iran

2 Institute of Biological Sciences, Damghan University, Damghan, Iran

3 Department of Gynecology and Obstetrics, Dietary Supplements and Probiotic Research Center, Alborz University of Medical Science, Karaj, Iran

4 Medical Microbiology Research Center, Qazvin University of Medical Sciences, Qazvin, Iran

5 Non-communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran

6 Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran

7 Department of Biology, Faculty of Basic Sciences, Hamedan branch, Islamic Azad University, Hamedan, Iran


Background: Vaginal microbiota are believed to profoundly impact the overall quality of life. Moreover, reduced levels of circulating estrogen are responsible for the majority of the changes in the genital tract in postmenopausal women. Accordingly, the present study aimed to investigate the effects of E. angustifolia (EA) on the genitourinary system in postmenopausal women.
Methods: In this double-blinded, randomized, placebo-controlled trial, we randomly assigned 58 postmenopausal women to one of the two medicinal herb-receiving (15 g of whole EA fruit powder) and placebo-receiving (7.5 g of isomalt+7.5 g of cornstarch) groups. Initially and after 10 weeks of the treatment, urinalysis, vaginal microbial culture, and vaginal pH measurement were carried out. This study was registered in the Iranian Registry of Clinical Trials with the code of IRCT20170227032795N4. Additionally, qualitative and quantitative data were analyzed using the Chi-square and the ANCOVA tests, respectively.
Results: The findings revealed that a 10-week treatment with EA had no significant effects on urine pH (5.733±1.014; P=0.728), specific gravity (1.022±0.006; P=0.438), as well as the count of red blood cells (1.533±2.562; P=0.080), white blood cells (3.750±7.109; P=0.349), and epithelial cells (2.116±1.798; P=0.595), and the qualitative parameters, including protein (P=0.612), blood (P=0.261), nitrite (P=0.483), bacteria (P=0.179), and mucus (P=0.564).
Conclusion: Oral consumption of EA did not significantly change the studied parameters. Thus, further studies with larger sample sizes, longer duration, subjects of different age groups, and other routes of administration could be suggested.


How to Cite: Rezaei A, Badehnoosh B, Mohammadbeigi M, Qorbani M, Emaminia F, Mohammadyari AR, Jalalvand F. Effects of Oral Use of Elaeagnus angustifolia L. on the Genitourinary Laboratory Findings in Postmenopausal Women: A Randomized, Double-Blind Clinical Trial. Women. Health. Bull. 2023;10(1):1-12. doi: 10.30476/whb.2023.97069.1203.


1. Muhleisen AL, Herbst-Kralovetz MM. Menopause and the vaginal microbiome. Maturitas. 2016;91:42–50. doi: 10.1016/j.maturitas.2016.05.015. PubMed PMID: 27451320. ## 2. Drew O, Sherrard J. Sexually transmitted infections in the older woman. Menopause Int. 2008;14(3):134–5. doi: 10.1258/mi.2008.008020. PubMed PMID: 18714080. ## 3. Salas-Jara MJ, Ilabaca A, Vega M, García A. Biofilm forming Lactobacillus: new challenges for the development of probiotics. Microorganisms. 2016;4(3):35. doi: 10.3390/microorganisms4030035. PubMed PMID: 27681929; PubMed Central PMCID: PMC5039595. ## 4. Ward K, Deneris A. An Update on Menopause Management. J Midwifery Womens Health. 2018;63(2):168–177. doi: 10.1111/jmwh.12737. PubMed PMID: 29522279. ## 5. Cancelo-Hidalgo MJ, Coello LB. Genitourinary Syndrome of the Menopause: Vaginal Health and Microbiota. In Cano A, editors: Menopause. Springer; 2017. p. 91–107. doi: 10.1007/978-3-319-59318-0. ## 6. Tehranizadeh ZA, Baratian A, Hosseinzadeh H. Russian olive (Elaeagnus angustifolia) as a herbal healer. BioImpacts. 2016;6(3):155-167. doi: 10.15171/bi.2016.22. PubMed PMID: 27853679; PubMed Central PMCID: PMC5108988. ## 7. Emaminia F, Rezaei A, Badehnoosh B, Ramezani R, Shabani M. The effects of Elaeagnus angustifolia L. whole fruit on the sex hormone profile in menopausal women: A double-blind, randomized, placebo-controlled study. J Ethnopharmacol. 2020;246:112229. doi: 10.1016/j.jep.2019.112229. PubMed PMID: 31513839. ## 8. Zeinalzadeh S, Mohagheghzadeh AA, Ahmadinezhad F, Akbarzadeh M. Comparison of the effect of Elaeagnus angustifolia flower capsule and sildenafil citrate tablet female sexual interest/arousal disorder in clinical trial study. J Fam Med Prim Care. 2019;8(11):3614-3620. doi: 10.4103/jfmpc.jfmpc_525_19. PubMed PMID: 31803662; PubMed Central PMCID: PMC6881950. ## 9. Akbarzadeh M, Zeinalzadeh S, Zolghadri J, Mohagheghzadeh A, Faridi P, Sayadi M. Comparison of Elaeagnus angustifolia Extract and Sildenafil Citrate on Female Orgasmic Disorders: A Randomized Clinical Trial. J Reprod Infertil. 2014;15(2):190–8. PubMed PMID: 25473627; PubMed Central PMCID: PMC4227976. ## 10. Khan SU, Khan A, Shah A-HA, Shah SM, Hussain S, Ayaz M, et al. Heavy metals content, phytochemical composition, antimicrobial and insecticidal evaluation of Elaeagnus angustifolia. Toxicol Ind Health. 2016;32(1):154–61. doi: 10.1177/0748233713498459. PubMed PMID: 24081630. ## 11. Farzaei MH, Bahramsoltani R, Abbasabadi Z, Rahimi R. A comprehensive review on phytochemical and pharmacological aspects of Elaeagnus angustifolia L. J Pharm Pharmacol. 2015;67(11):1467–80. doi: 10.1111/jphp.12442. PubMed PMID: 26076872. ## 12. Shabani M, Rezaei A, Badehnoosh B, Qorbani M, Yaseri M, Ramezani R, et al. The effects of Elaeagnus angustifolia L. on lipid and glycaemic profiles and cardiovascular function in menopausal women: A double‐blind, randomized, placebo‐controlled study. Int J Clin Pract. 2021;75(4):e13812. doi: 10.1111/ijcp.13812. PubMed PMID: 33145864. ## 13. Jalalvand F, Rezaei A, Badehnoosh B, Yaseri M, Qorbani M, Emaminia F, et al. The Effects of Elaeagnus angustifolia L. on the Thyroid-Stimulating Hormone, Dehydroepiandrosterone-Sulfate, Prolactin and Cortisol Levels in Post-Menopausal Women: A Double-Blind, Randomized, and Placebo-Controlled Study. Front Pharmacol. 2021;12:654459. doi: 10.3389/fphar.2021.654459. PubMed PMID: 34305584; PubMed Central PMCID: PMC8293672. ## 14. Qin J, Shi X, Xu J, Yuan S, Zheng B, Zhang E, et al. Characterization of the Genitourinary Microbiome of 1,165 Middle-Aged and Elderly Healthy Individuals. Front Microbiol. 2021;12:673969. doi: 10.3389/fmicb.2021.673969. PubMed PMID: 34489882; PubMed Central PMCID: PMC8417382. ## 15. Schulz KF, Altman DG, Moher D, CONSORT Group. CONSORT 2010 statement: updated guidelines for reporting parallel group randomised trials. Int J Surg. 2011;9(8):672-7. doi: 10.1016/j.ijsu.2011.09.004. PubMed PMID: 22019563. ## 16. Nikniaz Z, Mahdavi R, Nikniaz L, Ebrahimi A, Ostadrahimi A. Effects of Elaeagnus angustifolia L. on Lipid Profile and Atherogenic Indices in Obese Females: A Randomized Controlled Clinical Trial. Journal of Dietary Supplements. 2016;13(6):595–606. doi: 10.3109/19390211.2016.1150933. ## 17. Ebrahimi AA, Nikniaz Z, Ostadrahimi A, Mahdavi R, Nikniaz L. The effect of Elaeagnus angustifolia L. whole fruit and medulla powder on women with osteoarthritis of the knee: A randomized controlled clinical trial. E European Journal of Integrative Medicine. 2014;6(6):672–679. doi: 10.1016/j.eujim.2014.07.016. ## 19. Karimi G, Hosseinzadeh H, Rassoulzadeh M, Razavi BM, Taghiabadi E. Antinociceptive effect of Elaeagnus angustifolia fruits on sciatic nerve ligated mice. Iran J Basic Med Sci. 2010;13(3):97–101. ## 20. Hall GS. Bailey & Scott’s Diagnostic microbiology, 13th ed. American Society for Clinical Pathology; 2013. doi: 10.1309/LM5JC0PH0OGGBSZZ. ## 21. Fischbach FT, Dunning MB. A manual of laboratory and diagnostic tests. Lippincott Williams & Wilkins; 2009. ## 22. Chantziantoniou N, Donnelly AD, Mukherjee M, Boon ME, Austin RM. Inception and development of the Papanicolaou stain method. Acta Cytol. 2017;61(4–5):266–280. doi: 10.1159/000457827. PubMed PMID: 28384641. ## 23. Tao X, Austin RM, Zhang H, Zhang L, Xiao J, Wang L, et al. Pap Test Reporting Rates for Conventional Smear and Liquid-Based Cervical Cytology from the Largest Academic Women’s Hospital in China: Analysis of 1,248,785 Pap Test Reports. Acta Cytol. 2015;59(6):445–51. doi: 10.1159/000443679. PubMed PMID: 26789332. ## 24. Price TK, Wolff B, Halverson T, Limeira R, Brubaker L, Dong Q, et al. Temporal dynamics of the adult female lower urinary tract microbiota. mBio. 2020;11(2):e00475-20. doi: 10.1128/mBio.00475-20. PubMed PMID: 32317321; PubMed Central PMCID: PMC7175091. ## 25. Welch AA, Mulligan A, Bingham SA, Khaw KT. Urine pH is an indicator of dietary acid–base load, fruit and vegetables and meat intakes: results from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk population study. Br J Nutr. 2008;99(6):1335–43. doi: 10.1017/S0007114507862350. PubMed PMID: 18042305. ## 26. Otsuki M, Kitamura T, Goya K, Saito H, Mukai M, Kasayama S, et al. Association of urine acidification with visceral obesity and the metabolic syndrome. Endocr J. 2011;58(5):363-7. doi: 10.1507/endocrj.k10e-319. PubMed PMID: 21441701. ## 27. Pagana KD, Pagana TJ, Pagana TN. Mosby’s® Diagnostic and Laboratory Test Reference-E-Book. Elsevier Health Sciences; 2022. ## 28. Hamidpour R, Hamidpour S, Hamidpour M, Shahlari M, Sohraby M, Shahlari N, et al. Russian olive (Elaeagnus angustifolia L.): From a variety of traditional medicinal applications to its novel roles as active antioxidant, anti-inflammatory, anti-mutagenic and analgesic agent. J Tradit Complement Med. 2017;7(1):24–29. doi: 10.1016/j.jtcme.2015.09.004. PubMed PMID: 28053884; PubMed Central PMCID: PMC5198788. ## 29. Cansev A, Sahan Y, Celik G, Taskesen S, Ozbey H. Chemical properties and antioxidant capacity of Elaeagnus angustifolia L. fruits. Asian Journal of Chemistry. 2011;23(6):2661-2665. ## 30. Siener R, Hesse A. The effect of different diets on urine composition and the risk of calcium oxalate crystallisation in healthy subjects. Eur Urol. 2002;42(3):289–96. doi: 10.1016/s0302-2838(02)00316-0. PubMed PMID: 12234515. ## 31. Pohl HG, Groah SL, Pérez-Losada M, Ljungberg I, Sprague BM, Chandal N, et al. The urine microbiome of healthy men and women differs by urine collection method. Int Neurourol J. 2020;24(1):41-51. doi: 10.5213/inj.1938244.122. PubMed PMID: 32252185; PubMed Central PMCID: PMC7136448. ## 32. Koedooder R, Mackens S, Budding A, Fares D, Blockeel C, Laven J, et al. Identification and evaluation of the microbiome in the female and male reproductive tracts. Hum Reprod Update. 2018;25(3):298–325. doi: 10.1093/humupd/dmy048. PubMed PMID: 30938752. ## 33. Brotman RM, Shardell MD, Gajer P, Fadrosh D, Chang K, Silver MI, et al. Association between the vaginal microbiota, menopause status and signs of vulvovaginal atrophy. Menopause. 2014;21(5):450-8. doi: 10.1097/GME.0b013e3182a4690b. PubMed PMID: 24080849; PubMed Central PMCID: PMC3994184. ## 34. Costello EK, Stagaman K, Dethlefsen L, Bohannan BJM, Relman DA. The application of ecological theory toward an understanding of the human microbiome. Science. 2012;336(6086):1255–62. doi: 10.1126/science.1224203. PubMed PMID: 22674335; PubMed Central PMCID: PMC4208626. ## 35. Sánchez-Borrego R, Manubens M, Navarro MC, Cancelo MJ, Beltrán E, Duran M, et al. Position of the Spanish Menopause Society regarding vaginal health care in postmenopausal women. Maturitas. 2014;78(2):146–50. doi: 10.1016/j.maturitas.2014.03.003. PubMed PMID: 24720907. ## 36. Sadeghi M, Abbaspoor Z, Namjouyan F, Cheraghian B. Effect of Glycyrrhiza glabra vaginal cream on the mental symptoms of vaginal atrophy in postmenopausal women. IJOGI. 2018;21(4):53–61. doi: 10.22038/IJOGI.2018.11227. Persian. ## 37. Bosak Z, Iravani M, Moghimipour E, Haghighizadeh MH, Jelodarian P. Evaluation of the effect of chamomile vaginal gel on subjective symptoms of vaginal atrophy in postmenopausal women: a randomized clinical controlled trial. IJOGI. 2019;22(7):23–31. doi: 10.22038/IJOGI.2019.13814. Persian. ## 38. Ghazanfarpour M, Shokrollahi P, Khadivzadeh T, Baharian Sharghi N, Mirzaii Najmabadi K, Babakhanian M, et al. Effect of Foeniculum vulgare (fennel) on vaginal atrophy in postmenopausal women: a double-blind, randomized, placebo-controlled trial. Post Reprod Heal. 2017;23(4):171–176. doi: 10.1177/2053369117733629. PubMed PMID: 28990439. ## 39. Ghorbani Z, Mirghafourvand M, Khalili AF, Javadzadeh Y, Shakouri SK, Tabrizi AD. The Effect of Panax ginseng on Genitourinary Syndrome in Postmenopausal Women: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial. Complement Med Res. 2021;28(5):419–426. doi: 10.1159/000514944. PubMed PMID: 33730722. ## 40. Umland EM, Cauffield JS, Kirk JK, Thomason TE. Phytoestrogens as therapeutic alternatives to traditional hormone replacement in postmenopausal women. Pharmacotherapy. 2000;20(8):981–90. doi: 10.1592/phco.20.11.981.35259. PubMed PMID: 10939560. ##