Do antifungal medicines for vaginal yeast infections (thrush) work better if taken by mouth (orally) or placed in the vagina (intravaginally)?

What is thrush?

Thrush (also called candidiasis) is a common vaginal infection caused by a type of fungus called a yeast. Symptoms include itching and irritation around the vagina and a white discharge. Thrush is usually harmless but it can be uncomfortable.

Thrush is usually treated with antifungal medicines. These can be taken by mouth (orally) or placed in the vagina (intravaginally).

Why we did this Cochrane Review

We wanted to find out if oral antifungal medicines work better than intravaginal antifungal medicines to treat thrush infections.

What did we do?

We searched for studies of antifungal medicines to treat thrush that compared an oral antifungal with an intravaginal antifungal.

We looked for randomised controlled studies, in which the treatments received were decided at random, because these studies usually give the most reliable evidence about the effects of treatments.

We were interested in how well - and how fast - antifungal medicines could get rid of yeast infections and improve symptoms; whether they had any unwanted effects; and whether women preferred oral or intravaginal treatment.

Search date: we included evidence published up to 29 August 2019.

What we found

We found 26 studies in 5007 women with thrush who were treated with antifungal medicines called azoles. The studies were conducted in Europe, the USA, Thailand, Iran, Japan and Nigeria. Eight azoles were studied: 2 oral (fluconazole and itraconazole) and 6 intravaginal (butoconazole, clotrimazole, econazole, miconazole, sertaconazole and terconazole).

The studies measured whether oral and intravaginal antifungal medicines led to:

• no symptoms (clinical cure);
• no yeasts found in the vagina (mycological cure); or
• unwanted effects that caused women to stop treatment.

No studies reported the costs of the oral or intravaginal antifungal medicines.

What are the results of our review?

Clinical cure (no symptoms) was similar for oral and intravaginal antifungal medicines in both the short term (5 to 15 days; 13 studies), and long term (2 to 12 weeks; 9 studies). Whether an antifungal medicine is oral or intravaginal probably makes little to no difference to getting rid of thrush symptoms.

However, oral antifungal medicines probably cleared yeast from the vagina (mycological cure) better than intravaginal ones in both the short term (19 studies) and long term (13 studies).

Only three women stopped using their antifungal medicine because of unwanted effects (23 studies); the risk of women stopping treatment with oral or intravaginal antifungal medicines is low.

The numbers of unwanted effects reported were similar: whether an antifungal medicine is oral or intravaginal might make little to no difference to unwanted effects (13 studies). Headache and digestive symptoms were more common with oral antifungal medicines; unwanted effects of intravaginal antifungals commonly affected only the vaginal area.

Our results suggested that women might prefer taking an oral antifungal medicine to an intravaginal one (12 studies).

Whether an antifungal medicine is oral or intravaginal may make little to no difference to how quickly thrush gets better.

How reliable are these results?

We are moderately confident in our findings for clinical and mycological cure of thrush. These results might change if further evidence becomes available. We are confident about the low risk of women stopping treatment because of unwanted effects of antifungal medicines, and further evidence is unlikely change this.

We are less confident about the numbers of unwanted effects, preferred treatment, and how quickly symptoms get better. These results are likely to change if further evidence becomes available.

Ten studies received support from pharmaceutical companies; this could have affected how the studies were designed, conducted and reported. The results from some studies varied widely and were not reported consistently; and the women knew which treatment they had, which could have affected the results reported.

Conclusions

Oral antifungal medicines probably clear yeast from the vagina better than intravaginal antifungal medicines, although there is probably little to no difference between them for getting rid of thrush symptoms.

The risk of women stopping treatment because of unwanted effects is low for both oral and intravaginal antifungal medicines.

Authors' conclusions: 

Oral anti-fungal treatment probably improves short- and long-term mycological cure over intra-vaginal treatment for uncomplicated vaginal candidiasis. Oral treatment was the favoured treatment preference by participants, though the certainty of this evidence is low.

The decision to prescribe or recommend an anti-fungal for oral or intra-vaginal administration should take into consideration safety in terms of withdrawals and side effects, as well as cost and treatment preference. Unless there is a previous history of adverse reaction to one route of administration or contraindications, women who are purchasing their own treatment should be given full information about the characteristics and costs of treatment to make their own decision. If health services are paying the treatment cost, decision-makers should consider whether the higher cost of some oral anti-fungals is worth the gain in convenience, if this is the patient's preference.

Read the full abstract...
Background: 

Anti-fungals are available for oral and intra-vaginal treatment of uncomplicated vulvovaginal candidiasis.

Objectives: 

The primary objective of this review is to assess the relative effectiveness (clinical cure) of oral versus intra-vaginal anti-fungals for the treatment of uncomplicated vulvovaginal candidiasis. Secondary objectives include the assessment of the relative effectiveness in terms of mycological cure, in addition to safety, side effects, treatment preference, time to first relief of symptoms, and costs.

Search strategy: 

We searched CENTRAL, MEDLINE, Embase, and two trials registers on 29 August 2019 together with reference checking and citation searching.

Selection criteria: 

We included randomised controlled trials published in any language comparing at least one oral anti-fungal with one intra-vaginal anti-fungal in women (aged 16 years or over) with a mycological diagnosis (positive culture, microscopy for yeast, or both) of uncomplicated vulvovaginal candidiasis. We excluded trials if they solely involved participants who were HIV positive, immunocompromised, pregnant, breast feeding or diabetic.

Data collection and analysis: 

We used standard methodological procedures as recommended by Cochrane.

Main results: 

This review includes 26 trials (5007 participants). Eight anti-fungals are represented. All but three trials included participants with acute vulvovaginal candidiasis. Trials were conducted in Europe: UK (3), Croatia (2). Finland (2), the Netherlands (2), Germany (1), Italy (1), Sweden (1) and one trial across multiple European countries, USA (7) Thailand (2), Iran (2), Japan (1) and Africa (Nigeria) (1). The duration of follow-up varied between trials. The overall risk of bias of the included trials was high.

There was probably little or no difference shown between oral and intra-vaginal anti-fungal treatment for clinical cure at short-term follow-up (OR 1.14, 95% CI 0.91 to 1.43; 13 trials; 1859 participants; moderate-certainty evidence) and long-term follow-up (OR 1.07, 95% CI 0.77 to 1.50; 9 trials; 1042 participants; moderate-certainty evidence). The evidence suggests that if the rate of clinical cure at short-term follow-up with intra-vaginal treatment is 77%, the rate with oral treatment would be between 75% and 83%; if the rate of clinical cure at long term follow-up with intra-vaginal treatment is 84%, the rate with oral treatment would be between 80% and 89%. Oral treatment probably improves mycological cure over intra-vaginal treatment at short term (OR 1.24, 95% CI 1.03 to 1.50: 19 trials; 3057 participants; moderate-certainty evidence) and long-term follow-up (OR 1.29, 95% CI 1.05 to 1.60; 13 trials; 1661 participants; moderate-certainty evidence). The evidence suggests that if the rate of mycological cure at short-term follow-up with intra-vaginal treatment is 80%, the rate with oral treatment would be between 80% and 85%; if the rate of mycological cure at long-term follow-up with intra-vaginal treatment is 66%, the rate with oral treatment would be between 67% and 76%.

In terms of patient safety, there is a low risk of participants withdrawing from the studies due to adverse drug effects for either treatment (23 trials; 4637 participants; high-certainty evidence). Due to the low certainty of evidence, it is undetermined whether oral treatments reduced the number of side effects compared with intra-vaginal treatments (OR 1.04, 95% CI 0.84 to 1.29; 16 trials; 3155 participants; low-certainty evidence). The evidence suggests that if the rate of side effects with intra-vaginal treatment is 12%, the rate with oral treatment would be between 10% and 15%. We noted that the type of side effects differed, with intra-vaginal treatments being more often associated with local reactions, and oral treatments being more often associated with systemic effects including gastro-intestinal symptoms and headaches. Oral treatment appeared to be the favoured treatment preference over intra-vaginal treatment or no preference (12 trials; 2206 participants), however the data were poorly reported and the certainty of the evidence was low. There was little or no difference in time to first relief of symptoms between oral and intra-vaginal treatments: four trials favoured the oral treatment, four favoured intra-vaginal, one study reported no difference and one was unclear. The measurements varied between the 10 trials (1910 participants) and the certainty of the evidence was low. Costs were not reported in any of the trials.

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