Probiotics For Prevention of Recurrent Vulvovaginal Candidiasis: A Review
Probiotics For Prevention of Recurrent Vulvovaginal Candidiasis: A Review
Probiotics For Prevention of Recurrent Vulvovaginal Candidiasis: A Review
doi:10.1093/jac/dkl246
Advance Access publication 21 June 2006
Vulvovaginal candidiasis (VVC) is a common infection affecting the quality of life of many women.
Probiotics have been investigated as possible agents for the prevention of recurrences of VVC. We reviewed
the available literature. In some studies the development of VVC was associated with either a low number of
lactobacilli in the vagina or with the presence of H2O2-non-producing vaginal lactobacilli, although there are
a few studies not supporting these statements. In addition, in vitro studies have shown that lactobacilli can
inhibit the growth of Candida albicans and/or its adherence on the vaginal epithelium. The results of some
clinical trials support the effectiveness of lactobacilli, especially Lactobacillus acidophilus, Lactobacillus
rhamnosus GR-1 and Lactobacillus fermentum RC-14, administered either orally or intravaginally in colo-
nizing the vagina and/or preventing the colonization and infection of the vagina by C. albicans, while the
results of a small number of clinical trials do not corroborate these findings. Nevertheless, most of the
relevant clinical trials had methodological problems such as small sample size, no control group (placebo)
and included women without confirmed recurrent VVC, and thus they are not reliable for drawing definitive
conclusions. Thus, the available evidence for the use of probiotics for prevention of recurrent VVC is
limited. However, the empirical use of probiotics may be considered in women with frequent recurrence
of VVC (more than three episodes per year), especially for those who have adverse effects from or con-
traindications for the use of antifungal agents, since adverse effects of probiotics are very rare. In any case
women should be clearly informed about the unproven usefulness of probiotics for this purpose. In
conclusion, despite the promising results of some studies, further research is needed to prove the effective-
ness of probiotics in preventing the recurrences of VVC and to allow their wide use for this indication.
*Correspondence address. Alfa Institute of Biomedical Sciences (AIBS), 9 Neapoleos Street, 151 23 Marousi, Greece.
Tel: +30-694-611-0000; Fax: +30-210-683-9605; E-mail: [email protected]
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Review
and Canada were renamed as Lactobacillus reuteri RC-14 and The results of some studies associated VVC either with a
Lactobacillus casei GR-1 and L. casei var. rhamnosus was reduced number of lactobacilli or with species of lactobacilli
renamed as L. rhamnosus GR-1. However, in our review we not producing H2O2. In a study of 7918 pregnant women, Hillier
used the names of lactobacillus strains as they were mentioned et al. found that VVC was associated either with normal vaginal
in the cited articles. microbiota (dominated by lactobacilli) or with intermediate flora
(with decreased lactobacilli).12 Some other studies suggested that
pregnant13,14 or post-term15 women whose vaginas were
Literature search colonized by H2O2-producing lactobacilli were less likely to
have symptomatic VVC than those colonized with H2O2-non-
We searched for articles in the PubMed (1975–1/2006), from
producing vaginal lactobacilli. However, Hawes et al.16 sug-
which we also found some additional relevant references. The
gested that H2O2-producing lactobacilli do not protect against
keywords were ‘vulvovaginal candidiasis’, ‘candidal vaginitis’,
VVC. In a study of 182 women visiting a sexually transmitted
‘yeast vaginitis’, ‘fungal infections’, ‘probiotics’, ‘lactobacilli’,
disease clinic, 25 of whom developed VVC during a 2 year
‘bifidobacteria’. We focused on microbiological studies and clini-
follow-up, the absence of lactobacilli from the vagina was not
cal trials. Specifically, we found relevant information from origi-
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Clinical studies 4 women were dominated by lactobacilli. One week after the
beginning of the trial, lactobacilli dominated the vagina of all
In Table 1 we present some clinical trials that have been con- women and GR-1 and/or RC-14 were recovered from all of them.
ducted in order to evaluate the ability of orally or intravaginally No recurrences of yeast vaginitis appeared during the study and
administered lactobacilli to inhibit the vaginal colonization by follow-up.
yeast and prevent the recurrence of VVC. Reid et al.23 reported Reid et al.28 supported the possible ability of orally adminis-
the case of a 33-year-old woman with recurrent cystitis and VVC tered L. rhamnosus GR-1 and L. fermentum RC-14 (at a dose of
(20 episodes of VVC in 30 months), whose vagina was colonized more than 8 · 108 viable lactobacilli) to restore and maintain a
by L. casei var. rhamnosus GR-1 up to 7 weeks after the vaginal normal vaginal microbiota in a randomized clinical trial in 42
administration of one pessary of these lactobacilli. The woman women in the age range 17–50 years without symptoms of uro-
had no symptoms of vaginitis during this period and for the next genital infection at the start and during the study, 33 of whom
6 months during which two more pessaries were inserted into her reported a history of VVC. The women were randomly separated
vagina. into four groups; groups 1, 2 and 3 received daily orally capsules
A clinical trial suggesting the effectiveness of vaginal lacto- of GR-1/RC-14 at different dosages and group 4 received daily
bacilli for the treatment of VVC was conducted by Hilton
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Table 1. Characteristics of reviewed studies
First No. of
author Type of women Study Symptoms and signs of Cultures of vaginal swabs
(ref) study studied population Intervention VVC after intervention after intervention
Hilton prospective 28 recurrent VVC (>5/year) vaginal suppositories with improvement of symptoms 4/5 women with cultures
(1993)24 cohort and symptoms of VVC Lactobacillus GG and signs (# of erythema positive for Candida
(positive cultures for twice/day for 7 days and discharge) albicans before
Candida in 5 women) intervention: negative
cultures 7 days after the
completion of intervention
Williams randomized 164 HIV-positive group 1 (58 women): vaginal cases of VVC (culture- 34 culture-confirmed cases
(2001)25 controlled L. acidophilus weekly confirmed) in 21 months of VVC in 21 months
trial group 2 (50 women): vaginal (median) of follow up: relative risk for
clotrimazole weekly group 1: 9/58 (15.5%) development of VVC:
group 3 (56 women): placebo group 2: 7/50 (14%) group 1 compared with
group 3: 18/56 (32.1%) group 3: 0.5
group 2 compared with
group 3: 0.4
Reid randomized 64 no urogenital infection in group 1 (32 women): improvement of vaginal 4 weeks after start of
(2003)26 controlled the year prior to the study L. rhamnosus GR-1 + symptoms: 30% (group 1) intervention: increase in vaginal
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trial L. fermentum RC-14 versus 12% (group 2) lactobacilli: group 1 >
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versus 37% (group 2), P > 0.05
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Candida; thus, it is difficult to draw conclusions regarding the Lactobacilli have been frequently found to co-exist with Candida
effectiveness of probiotics against VVC. in the vaginal epithelium of women with VVC, while they are
Pirotta et al.31 also did not support the use of combinations of significantly reduced in women with BV. Some in vitro studies
specific lactobacilli, either given orally or intravaginally, for the and clinical trials had positive results regarding the effectiveness
prevention of post-antibiotic vulvovaginitis. They conducted a of some specific lactobacilli strains against C. albicans. However,
randomized, placebo-controlled, double-blind clinical trial in most of the trials either included a small sample of women or
non-pregnant women in the age range 18–50 years who received women with no confirmed episodes of VVC or were not placebo-
oral powder of L. rhamnosus and Bifidobacterium longum (Lac- controlled. Moreover, there were differences among the trials
tobac) twice daily and/or one vaginal pessary of L. rhamnosus, regarding the strain of the tested probiotic, its dosage and the
L. delbrueckii, L. acidophilus and Streptococcus thermophilus duration of treatment. It should be emphasized that the various
(Femilac) each night and/or oral and/or intravaginal placebo dur- probiotic strains have different properties and different effects on
ing 6 days of antibiotic administration for a non-gynaecological Candida; thus, results from studies testing one strain should not
infection and for 4 days afterwards. Four days after completion of be extrapolated to other strains. Consequently, it is difficult to
the intervention, post-antibiotic vulvovaginitis had developed in draw reliable conclusions from the existing studies. Probiotics,
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10. Jeavons H. Prevention and treatment of vulvovaginal candidiasis 25. Williams AB, Yu C, Tashima K et al. Evaluation of two self-care
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11. Demirezen S. The Lactobacilli-Candida relationship in cervico- 26. Reid G, Charbonneau D, Erb J et al. Oral use of Lactobacillus
vaginal smears. Cent Eur J Public Health 2002; 10: 97–9. rhamnosus GR-1 and L. fermentum RC-14 significantly alters vaginal
12. Hillier SL, Krohn MA, Nugent RP et al. Characteristics of three flora: randomized, placebo-controlled trial in 64 healthy women. FEMS
vaginal flora patterns assessed by gram stain among pregnant women. Immun Med Microbiol 2003; 35: 131–4.
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13. Hillier SL, Krohn MA, Klebanoff SJ et al. The relationship of
28. Reid G, Beuerman D, Heinemann C et al. Probiotic Lactobacillus
hydrogen peroxide-producing lactobacilli to bacterial vaginosis and
dose required to restore and maintain a normal vaginal flora. FEMS
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