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SISTEMATIC REVIEW

Vulvovaginitis and the Treatment of Asymptomatic


Partners: A Systematic Review and Metanalisis
Paulo Csar Giraldo1, Hugo Marcus Rodrigues2, Amanda G Melo2, Rose Luce do Amaral3,
Mauro Romero L Passos4, Jos Eleutrio Junior5, Ana Katherine Gonalves6

ABSTRACT
Introduction: treating sexual partners of women with vaginal candidiasis and bacterial vaginosis is an issue in debate. Despite the present recommendations
of the international guidelines to not to treat the asymptomatic sexual partners, this is a frequent practice between gynecologists. Objective: evaluate the
influence of treating asymptomatic sexual partner of women with recurrent vulvovaginitis. Methods: databases searched: PubMed, Embase, Scielo and
CINAHAL. Selection criteria: randomized clinical trials published from 1982 to 2012 were included. Studies involving pregnant women were excluded.
Methodological quality was assessed using the Jadad scale. Data collection and analysis: Review Manager 5.1 was used for statistical analysis. Results:
eight randomized clinical trials were included based on the chosen criteria: 1,088 women were enrolled. For bacterial vaginosis, the RR for cure was 1.00
(95%CI: 0.951.05) (p = 0.13), and for recurrence 0.84 (95%CI: 0.621.14) (p = 0.34). Vaginal candidiasis had a RR of 1.03 (95%CI: 0.941.14) (p = 0.48)
for cure, and 1.02 (95%CI: 0.771.33 p = 0.91) for recurrence. Conclusion: treatment of asymptomatic sexual partners of women with vaginal candidiasis
or bacterial vaginosis does not affect the cure or recurrence rates and may increase the risk of side effects and unnecessary financial costs.
Keywords: vulvovaginitis, bacterial vaginosis, candidiasis, partner, treatment

INTRODUCTION dence of VVC increases dramatically in the second decade of life,


Vulvovaginitis (VV) is a common complaint and one of the corresponding to the onset of sexual activity, when several factors
most frequent reasons patients seek gynecologists(1). Annually, ap- (tissue trauma, deposition of semen in the vaginal cavity, exagge-
proximately 10 million consultations are attributed to symptoms rated use of soaps and chemicals, hormonal changes) influence the
and signs of vaginal discharge(2). vulvovaginal ecosystem(13). The sexual transmission of Candida
Despite VV being a very relevant condition to women due to the can occur during intercourse, but the frequency and timing of in-
high personal and financial costs ensued, it is often minimized by wo- tercourse could influence the development of an acute crisis(14). The
men and the medical community. This repeatedly results in incorrect practice of oral sex has also emerged as one of the risk factors(15).
diagnosis and treatment by both women and doctors(1), resulting in Current studies have associated homosexual practices with an in-
exaggerated use of antibiotics and antifungals. crease in the prevalence of Candida in the female genitals(16). On
The main causes of VV are well established: bacterial vaginosis the other hand, some studies suggest that the role of sexual practice
(BV), vaginal candidiasis (VVC) and trichomoniasis (VT). Howe- in the establishment of VVC has been amplified(17,18).
ver several questions are debatable, such as best drug to be used, A recent study which proposed to evaluate the transmission of
treatment regiment and most appropriate route of administration. genital candidiasis among heterosexual couples could not prove se-
Since VT has been confirmed as a sexually transmitted disease xual acquisition(19). This study evaluated the Candida species found
(STD), the treatment of an asymptomatic partner is uncontested(3-5). in couples and found that only 25% of men and women had the
Some studies suggest that treatment of sexual partners of women same species of Candida, contradicting previous studies(15). In other
with BV could reduce recurrence rates from 5% to 20%. However, studies which have treated sexual partners of women with VVC, no
data evaluating the efficacy of this practice is controversial(6-8). In increase in cure rates, decline or recurrence was observed(17).
a well-designed clinical trial, Mengel et al. (1989) found a reduc- Currently, despite the existing technology for diagnosis and tre-
tion in recurrence rates in patients with BV whose partners were atment of VV, the role of sexual transmission has yet to be defi-
simultaneously treated(9). Nontheless, three other studies found no ned. The clarification of this controversy could avoid unnecessary
relationship between oral therapy of the partner and the recurrence treatment of sexual partners, thus reducing costs, side effects and
rates of women(10-12). conflict within the couple.
VVC cannot be established as a STD since the transmission of
the agent does not necessarily cause VV. It is known that the inci- OBJECTIVE
This study proposes to systematically evaluate the influence of
1 TitledProfessor of Gynecology and Obstetrics Department of Campinas asymptomatic partner treatment in the cure and recurrence of VV.
State University (UNICAMP).
2 Graduate Medicine student of Rio Grande do Norte Federal University.
3 Gynecologist doctor, Gynecology and Obstetrics Department, Campinas
METHODS
State University (UNICAMP). This study adhered to PRISMA guidelines(20).
4 associate Professor and Chief of the Division of Sexually Transmitted

Diseases of Fluminense Federal University. Inclusion criteria


5 Assistant Professor, Maternal and Child Health Department of Cear

Federal University (UFC).


Randomized controlled trials published in the last 30 years to
6 Associate Professor, Gynecology and Obstetrics Department of Rio assess the effectiveness of partner treatment in the cure and recur-
Grande do Norte Federal University (UFRN). rence of VV.
DST - J bras Doenas Sex Transm 2013;25(1):36-40 - ISSN: 0103-4065 - ISSN on-line: 2177-8264 DOI: 10.5533/DST-2177-8264-201325108
Vulvovaginitis and the Treatment of Asymptomatic Partners: A Systematic Review and Metanalisis 37

Exclusion criteria RESULTS


Women under 16 years of age, HIV+, pregnant, asymptomatic, Bacterial vaginosis
and sex workers were excluded. These groups represent populations Four randomized controlled trials were selected:
at increased or decreased risk for STDs, wherein the prevalence of Verjtorp et al. (1988)(10) conducted a major randomized double
disease differs from the general population. This could interfere with blind clinical trial with 117 women using 500 mg of metronidazole
the sensitivity and/or specificity of the analysis in this review. 2 x day for 7 days. Half of the partners were randomly treated with
the same treatment regimen or a placebo. Cure and recurrence rates
Search and selection of literature were similar among women with treated partners (cure: 51/54 and
Eligible studies were identified by searching the following databa- recurrence: 13/54) or placebo partners (cure: 44/53 and recurrence:
ses: PubMed, Embase, Scielo, CINAHAL, and Google scholar. The 14/53) (Table 1).
studies were identified by a literature search of databases following Moi et al. (1989)(4) in another double-blind randomized control-
medical subject heading terms and/or text words (Mesh Terms): (Tre- led trial with 241 women who were treated with 2 g of metronida-
atment) AND (Vulvovaginitis) OR (Candidiasis) OR (Moniliasis) OR zole, and repeated 2 days later. The partners were randomly treated
(Vaginitis, Monilia) OR (Vaginosis) OR (Vaginitis) OR (Trichomo- with the same dose of metronidazole. Cure and recurrence rates
nas) AND (Partners) AND (randomized controlled trial) OR (clinical were similar among women with treated partners (cure: 115/119
trial) OR (follow-up) OR (prospective) NOT (Pregnant Woman). and recurrence: 19/112) or placebo partners (cure: 111/113 and re-
The bibliographies of the identified publications were reviewed for currence: 14/106) (Table 1).
additional pertinent studies. No language restrictions were applied. Vutyavanich et al. (1993)(11) conducted a randomized clinical
Two researchers (AKG and HMR) searched for articles pu- trial of 250 Thai women treated with 2 g of tinidazole and a partner
blished up to May 2012. After searching the databases, 513 randomly treated to placebo or tinidazole. Cure and recurrence ra-
potentially relevant papers were identified, 102 of which were tes were similar among women with treated partners (cure: 111/122
excluded after review of titles. Next the abstracts of the 411 re- and recurrence: 43/117) or placebo partners (cure: 113/119 and re-
maining titles were read, removing a further 313 titles. Of the currence: 33/126) (Table 1).
98 remaining articles, 8 were duplicated among the databases, Colli et al. (1997)(5) carried out a randomized double-blind stu-
which left 90 articles for final reading and qualitative assessment
dy with 131 Italian women who were treated with 2% clindamycin
by the Jadad scale(21). The Jadad scale considered studies to be
in the form of vaginal cream for 7 days. The partners were ran-
methodologically adequate when they obtained a score of 3 or
domly treated with oral clindamycin or a placebo. Cure and recur-
more(21). Thus, studies obtaining 3 or more points (8 studies) were
rence rates were similar among women with treated partners (cure:
classified as high methodological quality and remained in the sys-
66/69 and recurrence: 5/38) or placebo partners (cure: 65/69 and
tematic review (Figure 1).
recurrence: 9/32) (Table 1).
The total RR for cure and recurrence were similar among women
Data extraction whose partners were treated or not for BV: cure RR 1.00 (95% CI:
Several characteristics of the original articles were extracted and 0.95-1.05) (p = 0.13) Recurrence RR 0.84 (95% CI: 0.62-1.14) (p
included in the systematic review. The data included the last name of = 0.34) (Figure 2).
the first author, the year of publication, country, number of subjects,
type of VV studied as well as type of intervention and results.
Vaginal candidiasis
Analysis Bishop et al. (1986)(22) conducted a double blind randomized
Statistical analysis was done using Review Manager (RevMan) clinical trial in Belgium with 117 women treated with 200 mg of
5.1 to provide a group analysis of the results of the selected clinical ketoconazole 2 x daily for 3 days whose partners were randomly
trials. The pooled analysis was obtained by analyzing the combi- treated with ketoconazole or placebo. Cure and recurrence rates
ned results of the chosen studies using the random effect model, were similar among women with treated partners (cure: 48/57 and
and then testing for heterogeneity using the Chi-square test. The recurrence: 13/48) or placebo partners (cure: 53/60 and recurrence:
homogeneity of the selected studies was realized. 19/53) (Table 1).

Cure

Figure 1 Study selection cure.


DST - J bras Doenas Sex Transm 2013;25(1):36-40
38 giraldo et al.

Table 1 Characteristics of selected randomized clinical trials for BV and VVC

Study Country Subjects Randomized Intervention Results

Treated cure: 51/54


Verjtorp (1988) 107 non-pregnant Women: 500 mg of metronidazol 2 x day/7days Recurrence: 13/54-
Denmark
women with BV Partners: 50% = same treatment, 50% = placebo Placebo cure: 44/53
Recurrence: 14/53

Treated cure: 115/119


Moi Women: 2 g of metronidazol 2 x day
241 non-pregnant Recurrence: 19/112
(1989) Denmark Partners: same treatment randomized
women with BV Placebo cure: 111/113
Recurrence: 14/106

Treated cure: 111/122


Vutyavanich Women: 2 g of tinidazol
250 non-pregnant Recurrence: 43/117
(1993) Thailand Partners: randomized tinidazol or placebo
women with BV Placebo cure: 113/119
Recurrence: 33/126

Treated cure: 66/69


Colli
Italy 131 non-pregnant Women: clindamycin 2% vaginal cream/ 7 days Recurrence: 5/38
(1997)
women with BV Partners: randomized oral clindamycin or placebo Placebo: cure: 65/69
Recurrence: 9/32

Treated cure: 48/57


Bishop (1986) 117 non-pregnant Women: 200 mg 2 x day ketoconazole for 3 days Recurrence: 13/48
Belgium
women with VVC Partners: randomized ketoconazole or placebo Placebo cure: 53/60
Recurrence: 19/53

Calderon-Marquez Treated cure: 17/20


44 non-pregnant Women: 200 mg 2 x day ketoconazole for 3 days Recurrence: 0/16
(1987) Mexico
women with VVC Partners: randomized ketoconazole or placebo Placebo cure: 15/19:
Recurrence: 2/15

Treated cure: 26/28


Fong 54 non-pregnant Women: 400 mg 2 x day ketoconazole for 7 days Recurrence: 8/26
Canada
(1992) women with VVC Partners: randomized 200 mg ketoconazole for 5 days Placebo cure: 15/19
Recurrence: 9/28

Shihadeh 144 non-pregnant Treated cure: 26/28


Women: 400 mg 2 x day ketoconazole for 7 days Recurrence: 8/26
(2000) Jordan women with VVC
Partners: half received randomized ketoconazole Placebo cure: 15/19
Recurrence: 9/28

Calderon-Marquez (1987)(23) carried out a randomized double- CI: 0.94-1.14) (p = 0.48), recurrence RR 1.02 (95% CI: 0.77-1.33)
-blind study which included 44 women who used 50 mg itracona- (Figure 3).
zole 2 x day for 5 days and their randomly treated partners. Cure
and recurrence rates were similar among women with treated par- Vaginal trichomoniasis
tners (cure: 17/20 and recurrence: 0/16) or placebo partners (cure: Interestingly, in the last 30 years no trials have been performed
15/19 and recurrence: 2/15) (Table 1). evaluating the indication of treatment of partners of women with
Fong et al. (1992)(24) conducted a randomized clinical trial with VT. The only randomized clinical trial was conducted over 30
54 Canadian women who received 400 mg of ketoconazole for 7 years ago; it was not possible to include it in this study. In 1981
days. The partner received 200 mg of ketoconazole for 5 days, or Lyng & Christensen(26) conducted a randomized clinical trial with
a placebo. Cure rates and recurrence were similar among women 118 women, which found that the persistence of the infection was
with treated partners (cure: 26/28 and recurrence: 8/26) or placebo significantly higher in the group which had no partner treatment
partners (cure: 15/19 and recurrence: 9/28) (Table 1). (14/59) compared to the group which did (3/59) (RR: 0.21, 95%
Shihadeh et al. (2000)(25) carried on a randomized clinical trial CI: 0.06-0.71). This difference persisted in the subgroup who
in Jordan with 144 women who received 400 mg of ketoconazole resumed sex with untreated partners. More recently, in a study
for 7 days. Half the partners received 400 mg ketoconazole for 7 testing the efficacy of intravaginal nonoxynol 9 for VT, Antonelli
days. Cure and recurrence rates were similar among women with et al. (2000)(27). observed that women whose partners were trea-
treated partners (cure: 57/72 and recurrence: 35/57) or placebo par- ted with metronidazole showed better cure rates compared those
tners (cure: 53/72 and recurrence: 28/53) (Table 1). whose partners went untreated. This study cannot be considered
The total RR for cure and recurrence was similar among women for this meta-analysis since the randomization, tracking was not
whose partners were treated or not for VVC: cure RR 1.03 (95% described.
DST - J bras Doenas Sex Transm 2013;25(1):36-40
Vulvovaginitis and the Treatment of Asymptomatic Partners: A Systematic Review and Metanalisis 39

Recurrence

Figure 2 Pooled analysis of selected BV studies.

Cure

Recurrence

Figure 3 Pooled analysis of selected VVC studies.

DISCUSSION We believe that the ban on placebo use in clinical trials in recent
years has impeded randomized trials(28). Since VT is considered a
The medical literature and most researchers suggest that sexu-
STD the consequence of prescribing a placebo instead of the tre-
al partners of women with VV should not be treated(27). However,
some national health programs, including Brazilian health servi- atment is not ethically accepted. In vivo studies in animal models
ces, treat VV erroneously as a STD and leave treatment to the dis- are a solution, even though they are difficult to perform. Even so,
cretion of gynecologists. Unfortunately this results in over treat- it is fundamental to encourage both studies in vitro and in animal
ment which increases costs and causes unnecessary physical side models, which are already well known for VVC, but not yet esta-
effects. There are also serious social and emotional implications blished for BV.
which cause conflict within the couple due to having transmitted a Contrary to VT, BV and VVC are caused by microorganisms
STD. Very few studies consider the latter or more importantly, the part of the normal microflora composition which sometimes assu-
microbial resistance resulting from this practice. me the role of pathogens.
Proponents of partner treatment argue that this practice could The pooled analysis suggested a slightly lowered risk of recur-
reduce recurrences in women as well as new transmissions. Ho- rence was from the group of women with partners treated for BV-
wever our findings do not confirm these VT assertions. VT seems -RR 0.84 (95% CI: 0.62-1.14), however no statistically significant
to be the only infectious VV wherein treating the partner increases values were found for cure rates. There was no difference betwe-
the chances of cure and reduces recurrence. This being said, the en the group of men who received a placebo and those who were
only study that confirms this hypothesis, by Lyng & Christensen(26), treated-RR: 1.00 (95% CI: 0.951.05).
was conducted in 1981. Besides this, it is accepted that VT is a The pooled analysis of studies on VVC suggests that the eviden-
protozoan and cannot be found in the vaginal cavity under normal ce pointing to asymptomatic partner treatment is much weaker than
conditions and is not part of the vaginal flora. It follows that VT for VB. The total RR for cure was 1.03 (95% CI: 0.94-1.14), and for
must be treated in both parties. recurrence 1.02 (95% CI: 0.77-1.33).
DST - J bras Doenas Sex Transm 2013;25(1):36-40
40 giraldo et al.

Therefore, it is evident from these results that partner treatment 15. Bradshaw CS, Morton AN, Garland SM, Morris MB, Moss LM, Fairley CK.
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No conflict of interest to declare. reol. 2011;25(2):145-51.
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