Introduction
Vaginal discharge is one of the common reasons for seeking consultation in women. The female reproductive system has a complex microbial flora where many physiological and pathological changes can be observed depending on various factors including age, menstrual period and the use of oral contraceptives. Physiologic vaginal discharge is colorless or white, odorless and without consequences. Studies have shown that the most common causes of abnormal vaginal discharge are candida vaginitis, bacterial vaginitis, and trichomoniasis [1, 2, 3]. Diagnosis of candidal vaginitis is based on the patient’s symptoms, accurate microscopic evaluation of vaginal secretions and evaluation of vaginal pH [4]. Approved treatments for this disease, which contributes to 41.4% of vaginitis, include a wide range of topical antifungal drugs that are typically used for 1-3 days as well as oral fluconazole 150 mg. Both topical and oral azole drugs cause relief of symptoms and negative culture in 80-90% of patients [5, 6, 7]. The treatments used today for chronic and recurrent fungal vaginitis infections are experimental. A one-week treatment with fluconazole can reduce the recurrence rate of vaginal candidiasis [8, 9]. The principles of the treatment are first based on complete treatment, and then maintenance treatment up to six months. Discontinuing the treatment in 50% of patients leads to the return of the infection. In treatment-resistant infections, auxiliary drugs such as ketoconazole and itraconazole should be used along with fluconazole. Considering the importance of knowing the best method of treatment in patients with candidal vaginitis, clinical trials are of particular importance. Considering the importance of the topic, this clinical trial aims to compare the effectiveness of boric acid and fluconazole and their side effects in the treatment of candidal vaginitis to the appropriate treatment method.

Methods
This is a non-blind randomized clinical trial that was conducted from November 2021 to January 2022 on 50 women with candidal vaginitis based on clinical and microbiological examinations who referred to hospitals affiliated to Iran University of Medical Sciences. Patients underwent clinical examination, direct smear of secretions, and cultures of secretions, and were included in the study if candidal vaginitis was confirmed. The observation of cheesy secretions, erythema, edema was considered as an inflammatory sign. Vaginal swab was performed for direct smear and secretion culture. Diagnosis and confirmation of patients’ vaginitis based on the patient’s symptoms, accurate microscopic evaluation of vaginal secretions in the laboratory, quantitative evaluation of white blood cells and evaluation of vaginal pH were also performed [4]. Identification of Candida species was done by colony morphology, germ tube test, hypha morphology and chlamydospore formation on corn meal agar, triphenyl tetrazolium chloride test, fermentation and absorption of different sugars, and sensitivity test to cycloheximide. 
The sample size was determined according to the results of Ray et al. [28] and based on the formula, considering α=0.05, β=0.2, P1=0.6, and P2=0.3. Based on the results, 46 women in two groups of 23 were considered. With an increase of 10% due to possible sample dropout, 25 people were considered for each group. After confirmation of candidal vaginitis, 46 women were included in the study and 4 were excluded. The obtained information was analyzed in SPSS software, version 26. In the descriptive analysis, frequency, percentage, and Mean±SD, were used. To determine the difference between the two groups and also between the two evaluation phases in two groups, chi-square test was used.

Results
The mean age in the boric acid group was 32±5.88 years, and in the fluconazole group as 31.5±3.85 years. The body mass index was 27.9 in the boric acid group and 27.1 in the fluconazole group. The comparison of underlying diseases is shown in Table 1, and the prevalence of symptoms before and after treatment in both groups is shown in Table 2.




Side effects of fluconazole use included gastrointestinal side effects among 3 women (13%) while the side effects of boric acid use included burning and skin side effects among 2 women (8.6%), and this difference was not significant (P>0.05).
In the boric acid group, 5 women had a positive culture after the treatment period (78% treatment response). In the fluconazole group, 7 women had a positive culture after the treatment period (69.5% treatment response). It shows the relative superiority of boric acid in improving the results of culture. Among 7 patients who still had positive cultures after the end of fluconazole treatment, 5 had diabetes and pre-diabetes (71%). Among 5 patients who still had positive cultures after finishing the treatment with boric acid, 3 had diabetes and pre-diabetes (40%). This shows the more suitable effect of boric acid in patients with diabetes and relative resistance to fluconazole in diabetic patients.

Conclusion
The rate of treatment success in the boric acid group was higher than in the fluconazole group and with fewer side effects, which indicated the superiority of boric acid. The percentage of improvement after treatment with boric acid is 78.2% and after treatment with fluconazole is 69.5%. The results of this study indicate the clinical use of boric acid as the first-line treatment for women with candidal vaginitis.

Ethical Considerations
Compliance with ethical guidelines
This study was approved by the Ethics Committee of Research and Technology, Iran University of Medical Sciences (Code: IR.IUMS.FMD.REC.1400.389).

Funding
This research did not receive any grant from funding agencies in the public, commercial, or non-profit sectors.

Authors' contributions
Conceptualization and supervision: Mahdiss Mohamadianamiri; Methodology and project administration: Majid Aklamli: Writing: Ainaz Sourati. 

Conflicts of interest
The authors declared no conflict of interest.


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