Weekly fluconazole therapy for recurrent vulvovaginal candidiasis: a systematic review and meta-analysis Maria I. Rosa a,b, *, Bruno R. Silva a , Patrı ´cia S. Pires a,b , Fa ´ bio R. Silva a , Napolea ˜o C. Silva b , Fa ´ bio R. Silva a , Sue ´ li L. Souza a , Kristian Madeira a,b,c,d , Ana P. Panatto a,b,c,d , Lidia R. Medeiros d a Laboratory of Epidemiology University of Extremo Sul Catarinense, Criciu ´ma, SC, Brazil b Postgraduate Program in Health Sciences, Health Sciences Unit, University of Extremo Sul Catarinense, Criciu ´ma, SC, Brazil c Sa˜o Jose ´ Hospital, Criciu ´ma, SC, Brazil d Departament of Gynecological Surgery at Hospital Ma ˜e de Deus, Porto Alegre, Brazil 1. Introduction Infection caused by Candida spp. affects 70–75% of women at least once during their lives, and 40–50% of them will experience at least one recurrence. About 5–8% of these women will have recurrent vulvovaginal candidosis (RVVC) [1], which is defined as four or more mycologically proven episodes within 12 months [2]. To date, little is known about the pathophysiology of RVVC. Previous reports suggest that vulvovaginal candidiasis (VVC) can be idiopathic or caused by several different mechanisms: familial susceptibility [3], pregnancy [4], oral contraceptives [5], the use of systemic antibiotics [6], diabetes mellitus [7], sexual behavior [8] and immunosuppression, such as taking corticosteroids or with HIV infection [9]. The treatment of women with recurrent infections can be difficult and frustrating. Most cases of RVVC are caused by identical Candida albicans strains [10]. Current choices are limited to azole medications, fungistatic drugs that inhibit synthesis of ergosterol, which is a major component of the fungal cell membrane. The most effective approach to treatment, particularly with C. albicans infections, seems to be maintenance antifungal therapy. Treatment options which have been studied and shown to be effective include ketoconazole [11], clotrimazole [12] and fluconazole [13]. Fluconazole has a quick pervasion and high concentrations in the vaginal tissue, besides which, it has a high water solubility and low protein binding. Its success also depends on its prolonged half- life in the vagina above the minimum inhibitory concentration (MIC) of most strains of C. albicans for a period of 96 h [14]. We carried out a systematic review and meta-analysis of the effectiveness, compared with placebo, of weekly fluconazole therapy for six months for recurrent RVVC, analyzing the clinical recurrence of vulvovaginal candidiasis and positive culture in Sabouraud dextrose agar immediately after the fluconazole treatment, 3 months after treatment and 6 months after treatment. 2. Methods 2.1. Inclusion and exclusion criteria To be eligible for inclusion in our systematic review, studies had to examine specific treatments with weekly fluconazole therapy for six months for recurrent vulvovaginal candidiasis, compared with placebo. We included only randomized clinical trials with the European Journal of Obstetrics & Gynecology and Reproductive Biology 167 (2013) 132–136 A R T I C L E I N F O Article history: Received 11 April 2012 Received in revised form 1 November 2012 Accepted 1 December 2012 Keywords: Systematic review Meta-analysis Fluconazol Vulvovaginal candidiasis A B S T R A C T Objective: To investigate the efficacy, compared to placebo, of fluconazole 150 mg weekly, given for six months as prophylaxis against recurrent vulvovaginal candidiasis (RVVC). Study design: A quantitative systematic review was performed, and randomized controlled trials were included. We conducted searches at Medline, EMBASE, Lilacs, Cochrane Library and ICI Web of Science from 1980 to March 2012. We used the odds ratio (OR) with confidence intervals (CI) of 95% using a random effects model of Mantel-Haenszel. The software used was Review Manager version 5.0. Results: Through the search strategies we identified 249 articles, of which only two were part of the meta-analysis. Fluconazole was more effective than placebo in reducing symptomatic episodes of VVC, immediately after treatment (OR 0.10, 95% CI 0.03–0.34), 3 months after treatment (OR 0.23, 95% CI 0.07–0.74) and 6 months after treatment (OR 0.39, 95% CI 0.24–0.64). Conclusion: Weekly treatment with fluconazole (150 mg) for six months is effective against RVVC. ß 2012 Elsevier Ireland Ltd. All rights reserved. * Corresponding author at: Rua Cruz e Souza, 510, Bairro Pio Correa-CEP 88811- 550, Criciu ´ ma, SC, Brazil. Tel.: +55 48 34339976; fax: +55 48 34335766. E-mail address: mir@unesc.net (M.I. Rosa). Contents lists available at SciVerse ScienceDirect European Journal of Obstetrics & Gynecology and Reproductive Biology jou r nal h o mep ag e: w ww .elsevier .co m /loc ate/ejo g rb 0301-2115/$ – see front matter ß 2012 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ejogrb.2012.12.001