Abstract
Background: In addition to physical discomfort, recurrent vulvovaginal candidiasis imposes a significant financial and psychosocial burden, such as lower levels of self-esteem, a higher level of stress, clinical depression, and less satisfaction with their life. Recurrent vulvovaginal candidiasis interferes with emotional and sexual relationships.
Objective: This study aimed to compare the effect of vaginal Salvia officinalis, clotrimazole, and their combination on the prevention of recurrent vulvovaginal candidiasis.
Methods: This randomized triple-blinded trial was conducted on 111 women aged 18-49 years with vulvovaginal candidiasis. Participants were randomly assigned into one of the three groups of vaginal tablets of Salvia officinalis 400 mg and placebo of clotrimazole 100 mg, clotrimazole 100 mg and placebo of Salvia officinalis 400 mg, or Salvia officinalis and clotrimazole that were applied every night for 7 consecutive days. A recurrence rate of vulvovaginal candidiasis was evaluated by WET test and vaginitis symptoms examination after 12 weeks. In the case of positive evaluation, the culture of vaginal discharge was performed.
Results: Totally, 29 patients (80.6%) in group clotrimazole, 33 patients (94.3%) in group Salvia officinalis and 35 patients (97.2%) in group Salvia officinalis-clotrimazole were treated (P = 0.43). Out of cured patients, 4 (13.8%) patients in the group clotrimazole, 1 patient (3%) in group Salvia officinalis, and no case in group Salvia officinalis-clotrimazole experienced the recurrence of infection. There was a significant difference among the 3 groups in terms of recurrence (P = 0.023). Moreover, no adverse event during the 12 weeks after treatment was observed.
Conclusion: Adjuvant therapy of Salvia officinalis alongside routine vaginal clotrimazole could successfully prevent recurrent vulvovaginal candidiasis after three months.
Graphical Abstract
[1]
Mitchell H. Vaginal discharge-causes, diagnosis, and treatment. BMJ 2004; 328(7451): 1306-8.
[http://dx.doi.org/10.1136/bmj.328.7451.1306] [PMID: 15166070]
[http://dx.doi.org/10.1136/bmj.328.7451.1306] [PMID: 15166070]
[2]
Dovnik A, Golle A, Novak D, Arko D, Takač I. Treatment of vulvovaginal candidiasis: A review of the literature. Acta Dermatovenerol Alp Panonica Adriat 2015; 24(1): 5-7.
[http://dx.doi.org/10.15570/actaapa.2015.2] [PMID: 25770305]
[http://dx.doi.org/10.15570/actaapa.2015.2] [PMID: 25770305]
[3]
Decherney A, Nathan L, Laufer N, Roman A. Current diagnosis & treatment obstetrics and gynecology. (11th ed.), Columbus, Ohio: McGraw-Hill Companies 2013.
[4]
Sobel JD, Faro S, Force RW, Foxman B, Ledger WJ, Nyirjesy PR. Vulvovaginal candidiasis: Epidemiologic, diagnostic, and therapeutic considerations. Am J Obstet Gynecol 1998; 178: 203e11.
[http://dx.doi.org/10.1016/S0002-9378(98)80001-X]
[http://dx.doi.org/10.1016/S0002-9378(98)80001-X]
[5]
Tehrani R, Farahmand M, Abedini MZH. Prevalance of vaginitis in iranian women symtoms and clinical association. Med Sci J Islamic Azad Uni-Tehran Med 2012; 22(1): 62-8.
[6]
Namazi A, Sehati P, Adibpur M, Mazloomi AS, Mohammad Alizadeh S. Prevalence and risk factors for candidiasis infection in women referring to health centers of Tabriz. J Med Sci Health 2008; 15(1): 67-1.
[7]
Sobel JD. Vulvovaginal candidosis. Lancet 2007; 369(9577): 1961-71.
[http://dx.doi.org/10.1016/S0140-6736(07)60917-9] [PMID: 17560449]
[http://dx.doi.org/10.1016/S0140-6736(07)60917-9] [PMID: 17560449]
[8]
Nedovic B, Posteraro B, Leoncini E, Ruggeri A, Amore R, Sanguinetti M. Polymorphism and vulvovaginal candidiasis: A systematic review and metaanalysis. BioMed Res Int 2014; 2014: 7.
[http://dx.doi.org/10.1155/2014/738298]
[http://dx.doi.org/10.1155/2014/738298]
[10]
Hong E, Dixit S, Fidel PL, Bradford J, Fischer G. Vulvovaginal candidiasis as a chronic disease: Diagnostic criteria and definition. J Low Genit Tract Dis 2014; 18: 31-8.
[11]
Irving G, Miller D, Robinson A, Reynolds S, Copas AJ. Psychological factors associated with recurrent vaginal candidiasis: A preliminary study. Sex Transm Infect 1998; 74: 334-8.
[http://dx.doi.org/10.1136/sti.74.5.334]
[http://dx.doi.org/10.1136/sti.74.5.334]
[12]
Fromtling RA. Overview of medically important antifungal azole derivatives. Clin Microbiol Rev 1988; 1: 187-217.
[http://dx.doi.org/10.1128/CMR.1.2.187]
[http://dx.doi.org/10.1128/CMR.1.2.187]
[13]
MacNeill C, Weisz J, Carey JC. Clinical resistance of recurrent Candida albicans vulvovaginitis to fluconazole in presence and absence of in vitro resistance. J Reprod Med 2003; 48: 63-8.
[14]
Marchaim D, Lemanek L, Bheemreddy S, Kaye KS, Sobel JD. Fluconazole resistant Candida albicans vulvovaginitis. Obstet Gynecol 2012; 120(6): 1407-14.
[http://dx.doi.org/10.1097/AOG.0b013e31827307b2]
[http://dx.doi.org/10.1097/AOG.0b013e31827307b2]
[16]
Horowitz BJ. Mycotic vulvovaginitis: A broad overview. Am J Obstet Gynecol 1991; 165(4): 1188-92.
[http://dx.doi.org/10.1016/S0002-9378(12)90725-5] [PMID: 1951573]
[http://dx.doi.org/10.1016/S0002-9378(12)90725-5] [PMID: 1951573]
[17]
Odds FC. Candida and candidosis: A review and bibliography. (2nd ed.). Bailliere Tindall London 1988; p. 124.
[18]
Allsworth JE, Peipert JF. Prevalence of bacterial vaginosis: 2001–2004 national health and nutrition examination survey data. Obstet Gynecol 2007; 109(1): 114-20.
[http://dx.doi.org/10.1097/01.AOG.0000247627.84791.91] [PMID: 17197596]
[http://dx.doi.org/10.1097/01.AOG.0000247627.84791.91] [PMID: 17197596]
[19]
Naeini A, Khosravi AR, Chitsaz M, Shokri H, Kamlnejad M. Anti Candida albicans activity of some Iranian plants used in traditional medicine. J Mycol Med 2009; 19(3): 168-72.
[http://dx.doi.org/10.1016/j.mycmed.2009.04.004]
[http://dx.doi.org/10.1016/j.mycmed.2009.04.004]
[20]
Runyoro DKB, Matee MIN, Ngassapa OD, Joseph CC, Mbwambo ZH. Screening of Tanzanian medicinal plants for anti-Candida activity. BMC Complement Altern Med 2006; 6(1): 11.
[http://dx.doi.org/10.1186/1472-6882-6-11] [PMID: 16571139]
[http://dx.doi.org/10.1186/1472-6882-6-11] [PMID: 16571139]
[21]
Mendling W, Krauss C, Fladung B. A clinical multicenter study comparing efficacy and tolerability of topical combination therapy with clotrimazole (Canesten, two formats) with oral single dose fluconazole (Diflucan) in vulvovaginal mycoses. Mycoses 2004; 47(3-4): 136-42.
[http://dx.doi.org/10.1111/j.1439-0507.2004.00970.x] [PMID: 15078430]
[http://dx.doi.org/10.1111/j.1439-0507.2004.00970.x] [PMID: 15078430]
[22]
WHO monographs on medicinal plants commonly used in the newly independent states 2010. Available from: http://repositorio.ub.edu.ar/handle/123456789/5157
[23]
Blumenthal M, Ed. The Complete German Commission E monographs Therapeutic guide to herbal medicines. Austin, TX: American Botanical Council 1998.
[24]
Cross EW, Park S, Perlin DS. Cross-resistance of clinical isolates of Candida albicans and Candida glabrata to over-the-counter azoles used in the treatment of vaginitis. Microb Drug Resist 2000; 6(2): 155-61.
[http://dx.doi.org/10.1089/107662900419474] [PMID: 10990271]
[http://dx.doi.org/10.1089/107662900419474] [PMID: 10990271]
[25]
Ahangari F, Farshbaf-Khalili A, Javadzadeh Y, Adibpour M, Sadeghzadeh Oskouei B. Comparing the effectiveness of Salvia officinalis, clotrimazole and their combination on vulvovaginal candidiasis: A randomized, controlled clinical trial. J Obstet Gynaecol Res 2019; 45(4): 897-907.
[http://dx.doi.org/10.1111/jog.13918] [PMID: 30663184]
[http://dx.doi.org/10.1111/jog.13918] [PMID: 30663184]
[26]
Nazari T. Comparison of itraconazole and clotrimazole in treatment of vulvo vaginal candidasis. Majallah-i Danishgah-i Ulum-i Pizishki-i Babul 2007; 8(6): 24-0.
[27]
Center for drug evaluation and research (CDER). Guidance for industry. 2016. Available from: https://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm509411.pdf
[28]
Farshbaf-Khalili A, Mohammadi-Ghalehbin B, Shahnazi M, Asghari S, Javadzadeh Y, Azghani P. Comparing the effect of garlic, Zataria multiflora and clotrimazole vaginal cream 2% on improvement of fungal vaginitis: A randomized controlled trial. Iran Red Crescent Med J 2016; 18(12): e29262.
[http://dx.doi.org/10.5812/ircmj.29262]
[http://dx.doi.org/10.5812/ircmj.29262]
[29]
Brojeni BSH, Mobini GR, Rafiyan Kopani M, Rasti Brojeni M, Sereshti M. The effect of Salvia officinalis extract and clotrimazole laboratory on vaginal candida isolated from women with vaginal candidiasis. Yafteh 2016; 17(1): 95-103.
[30]
Pinto E, Salgueiro LR, Cavaleiro C, Palmeira A, Gonçalves MJ. In vitro susceptibility of some species of yeasts and filamentous fungi to essential oils of Salvia officinalis. Ind Crops Prod 2007; 26(2): 135-41.
[http://dx.doi.org/10.1016/j.indcrop.2007.02.004]
[http://dx.doi.org/10.1016/j.indcrop.2007.02.004]
[31]
Jasim R, Al-khaliq I. Inhibitory effect of aqueous Salvia officinalis’s leaves in the growth of Candida albicans from infected women with vaginal candidiasis. Al-Kindy College Med J 2011; 6: 47-9.
[32]
Veličković D, Randjelovic N, Ristić M, Veličković A, Šmelcerović A. Chemical constituents and antimicrobial activity of the ethanol extracts obtained from the flower, leaf and stem of Salvia officinalis L. J Serb Chem Soc 2003; 68(1): 17-24.
[http://dx.doi.org/10.2298/JSC0301017V]
[http://dx.doi.org/10.2298/JSC0301017V]
[33]
de Freitas Araújo MG, Hilário F, Vilegas W, et al. Correlation among antioxidant, antimicrobial, hemolytic, and antiproliferative properties of Leiothrix spiralis leaves extract. Int J Mol Sci 2012; 13(7): 9260-77.
[http://dx.doi.org/10.3390/ijms13079260] [PMID: 22942765]
[http://dx.doi.org/10.3390/ijms13079260] [PMID: 22942765]
[34]
Caturla N, Vera-Samper E, Villalaín J, Mateo CR, Micol V. The relationship between the antioxidant and the antibacterial properties of galloylated catechins and the structure of phospholipid model membranes. Free Radic Biol Med 2003; 34(6): 648-62.
[http://dx.doi.org/10.1016/S0891-5849(02)01366-7] [PMID: 12633742]
[http://dx.doi.org/10.1016/S0891-5849(02)01366-7] [PMID: 12633742]
[35]
Damjanovic-Vratnica B, Ðakov T, Šukovic D, Damjanovic J. Chemical composition and antimicrobial activity of essential oil of wild-growing Salvia officinalis L. from Montenegro. J Essent Oil-Bear Plants 2008; 11(1): 79-89.
[http://dx.doi.org/10.1080/0972060X.2008.10643602]
[http://dx.doi.org/10.1080/0972060X.2008.10643602]
[36]
Martins N, Barros L, Santos-Buelga C, Henriques M, Silva S, Ferreira ICFR. Evaluation of bioactive properties and phenolic compounds in different extracts prepared from Salvia officinalis L. Food Chem 2015; 170: 378-85.
[http://dx.doi.org/10.1016/j.foodchem.2014.08.096] [PMID: 25306360]
[http://dx.doi.org/10.1016/j.foodchem.2014.08.096] [PMID: 25306360]
[37]
Sookto T, Srithavaj T, Thaweboon S, Thaweboon B, Shrestha B. In vitro effects of Salvia officinalis L. essential oil on Candida albicans. Asian Pac J Trop Biomed 2013; 3(5): 376-80.
[http://dx.doi.org/10.1016/S2221-1691(13)60080-5] [PMID: 23646301]
[http://dx.doi.org/10.1016/S2221-1691(13)60080-5] [PMID: 23646301]
[38]
Hayouni EA, Chraief I, Abedrabba M, Bouix M, Leveau J-Y, Mohammed H. Tunisian Salvia officinalis L. and Schinus molle L.(2008). essential oils: Their chemical compositions and their preservative effects against Salmonella inoculated in minced beef meat. Int J Food Microbiol 2008; 125(3): 242-51.
[39]
Soliman S, Alnajdy D, El-Keblawy A, Mosa K, Khoder G, Noreddin A. Plants’ natural products as alternative promising anti-Candida drugs. Pharmacogn Rev 2017; 11(22): 104-22.
[http://dx.doi.org/10.4103/phrev.phrev_8_17] [PMID: 28989245]
[http://dx.doi.org/10.4103/phrev.phrev_8_17] [PMID: 28989245]
[40]
Pistorius A, Willershausen B, Steinmeier EM, Kreisler M. Efficacy of subgingival irrigation using herbal extracts on gingival inflammation. J Periodontol 2003; 74(5): 616-22.
[http://dx.doi.org/10.1902/jop.2003.74.5.616] [PMID: 12816293]
[http://dx.doi.org/10.1902/jop.2003.74.5.616] [PMID: 12816293]
[41]
Okuyama T, Matsuda M, Masuda Y, Baba M, Masubuchi H, Adachi M. Studies on cancer bio-chemoprevention of natural resources. X. Inhibitory effect of spices on TPA-enhanced 3H-choline incorporation in phospholipid of C3H10T1/2 cells and on TPA-induced ear edema. Zhonghua Yaoxue Zazhi 1995; 47(5): 421-30.
[42]
Baricevic D, Sosa S, Della Loggia R, et al. Topical anti-inflammatory activity of Salvia officinalis L. leaves: The relevance of ursolic acid. J Ethnopharmacol 2001; 75(2-3): 125-32.
[http://dx.doi.org/10.1016/S0378-8741(00)00396-2] [PMID: 11297842]
[http://dx.doi.org/10.1016/S0378-8741(00)00396-2] [PMID: 11297842]
[43]
Kianbakht S, Dabaghian FH. Improved glycemic control and lipid profile in hyperlipidemic type 2 diabetic patients consuming Salvia officinalis L. leaf extract: A randomized placebo controlled clinical trial. Complement Ther Med 2013; 21(5): 441-6.
[http://dx.doi.org/10.1016/j.ctim.2013.07.004] [PMID: 24050577]
[http://dx.doi.org/10.1016/j.ctim.2013.07.004] [PMID: 24050577]
[44]
Atai Z, Ansari M, Ayatelahi Mousavi A, Mirzaei A. In-vitro study of antifungal effects of selected herbal extracts on standard and wild strains of Candida albicans. J Islam Dent Assoc Iran 2007; 19: 91-7. [In Persian]
[45]
Sobel JD, Wiesenfeld HC, Martens M, et al. Maintenance fluconazole therapy for recurrent vulvovaginal candidiasis. N Engl J Med 2004; 351(9): 876-83.
[http://dx.doi.org/10.1056/NEJMoa033114] [PMID: 15329425]
[http://dx.doi.org/10.1056/NEJMoa033114] [PMID: 15329425]
