Women with Candida spp on microscopy, compared with microscopy-negative women, were more likely to be aged less than 28 years, nulliparous, in full-time work or study, and to be more than 17 days from last menses (P < .05). When only women not taking oral contraceptives were examined (n = 148), the association between Candida spp on microscopy and being in the luteal phase of the menstrual phase was slightly greater, crude odds ratio (cOR) 3.7 (95% confidence interval [CI] 1.4–10.1), P < .01. Women with Candida spp on microscopy were more likely to practice receptive anal sex and to have frequent vaginal sex in the prior 3 months, to douche or wash intravaginally, and to have a history of genital herpes and gonorrhea. They were less likely to have had a new sexual partner in the prior 3 months and a history of genital warts (P = .05) and to have fewer male partners in the prior 3 months, although this was not statistically significant.
The demographic and behavioral characteristics in women with Candida spp on culture were compared with women without Candida spp on culture (data not shown). Although the findings were similar to those observed for Candida spp on microscopy, women with Candida spp on culture were more likely to have both given oral sex (cOR 1.9 [95% CI 1.0–3.8], P = .04) and to have received oral sex (2.4[95% CI 1.2–4.6], P = .01) in the last 3 months, to have used condoms inconsistently for vaginal sex (cOR for 100% condom use 0.4[95% CI 0.2–0.8], P < .01), to have had fewer lifetime sexual partners (cOR for > 12 lifetime partners 0.6[95% CI 0.4–1.0], P = .03), and to be more than 17 days from last menses (1.9[95% CI 1.1–3.1], P = .02).
Factors in the univariate analysis that were significantly associated with bacterial vaginosis (P < .05), as well as age and commercial sex work, which have been correlated with bacterial vaginosis in other studies, were entered into a logistic regression model (Table 1). The factors that remained significantly associated with bacterial vaginosis in the multivariate analysis included having a new sexual partner and more than 2 male sexual partners in the last year, more frequent vaginal sex, a past history of trichomoniasis, smoking, and Australian nationality. A negative association between oral contraception and bacterial vaginosis was observed that was of borderline statistical significance (P = .08). It was noted that if days since last menses was included in the logistic regression model, then no significant changes occurred in other variables in the model, but a significant negative association between oral contraception and bacterial vaginosis was seen in the study population, adjusted odds ratio (aOR) 0.6 (95% CI 0.4–1.0), P = .04. However, menstrual phase was not included in the main multivariate model owing to the high numbers of women on oral contraception and the potential interaction between these variables. There were insufficient numbers to examine the associations between bacterial vaginosis and menstrual phase in women not taking oral contraceptives.
All characteristics that were significantly associated in the univariate analysis with Candida spp on microscopy were entered into a logistic regression model (Table 1). Factors that were significantly associated with Candida spp on microscopy included douching or intravaginal washing and a history of gonorrhea (P < .01), although few women in the study had a history of gonorrhea (n = 9). A new sexual partner in the last 3 months and a history of genital warts were negatively associated with Candida spp. on microscopy. We did not include days since last menses in the main multivariate model due to the potential interaction between oral contraception and menstrual phase, which has previously been mentioned. However, if days since last menses was included in the logistic regression model, then no significant change occurred in the other variables in the model, and candidiasis on microscopy was associated with being more than 17 days since last menses in the study population (aOR 2.3 [95% CI 1.1–4.8], P = .03). When factors that had been associated with Candida spp. on culture were entered into a logistic regression model, receptive oral sex in the prior 3 months (aOR 2.4 [95% CI 1.1–5.3], P = .03) and nulliparity (aOR for past pregnancy 0.5 [95% CI 0.3–0.9], P = .03) remained significantly associated with Candida spp. on culture (full data not shown).
To better define risk factors for bacterial vaginosis, we compared demographic and behavioral factors associated with bacterial vaginosis to those associated with vaginal candidiasis. Women with bacterial vaginosis report specific high-risk sexual behaviors that are associated with sexually transmitted infections, whereas women with candidiasis do not. The significant behavioral differences between bacterial vaginosis and vaginal candidiasis support the concept that bacterial vaginosis may be sexually transmitted.
Women with bacterial vaginosis differed from women with candidiasis in this study in both demographics and sexual practices. Bacterial vaginosis was associated with sexual practices that are related to sexually transmitted infections, such as a high number of recent and lifetime sexual partners, a recent change in sexual partner, and a history of sexually transmitted infections and pregnancy. Other studies have reported associations between bacterial vaginosis and risk factors for sexually transmitted infections,9–13 and a study comparing women with chlamydial infection to women with bacterial vaginosis showed that both bacterial vaginosis and Chlamydia were associated with increased number of recent and lifetime sexual partners, a recent change of sexual partner, and higher rates of high-risk sexual behaviors.12
The presence of vaginal Candida spp on microscopy and on culture was associated with specific sexual practices in this study; however, the high-risk behaviors associated with bacterial vaginosis were not seen. Women with vaginal Candida spp were less likely to have had a recent new sexual partner, and were more likely to be nulliparous, to douche, and to practice oral and anal sex. Several studies have reported an association between candidiasis and orogenital sex,14–16 although to our knowledge no association has been shown with receptive anal sex. Higher rates of oral and rectal carriage in women with recurrent vulvovaginal candidiasis17 and concordance in Candida spp. between male and female sexual partners have been reported,18 indicating that inoculation of the vagina after either oral or anal sex could promote colonization and symptomatic infection. Although both conditions were associated with more frequent vaginal sex, inconsistent condom use was only associated with candidiasis and not bacterial vaginosis. Some studies have shown consistent condom use to be protective against candidiasis, and others have shown it to be protective against bacterial vaginosis.11,19,20 However, self-reported condom use can be affected by recall bias, which may explain the lack of consistency between studies.
The hormonal associations for bacterial vaginosis and candidiasis in this study differed. Bacterial vaginosis was negatively associated with oral contraceptive use, and there was a trend toward occurrence in the first 17 days of the menstrual cycle, whereas candidiasis tended to occur in the luteal phase of the cycle. An association between bacterial vaginosis and the follicular phase of the menstrual cycle21 and candidiasis and the luteal phase22 has been previously shown. Several studies have also reported a negative association between oral contraception and bacterial vaginosis,19,21,23 and candidiasis has been associated with higher-dose oral contraceptives.13,22,24 It has been suggested that estrogen increases epithelial cell receptivity and the glycogen content of epithelial cells, promoting growth of candidiasis, whereas glycogen also serves as a substrate for lactobacilli to produce lactic acid, a potent inhibitor of bacterial vaginosis-associated organisms.23
Smoking was associated with bacterial vaginosis in this study, a finding that has previously been reported. The association has been shown to be dose dependent and has persisted after controlling for sexual risk behaviors and alcohol use.9,11,25,26 We did not control for alcohol use in our study; however, the adjusted odds ratio for smoking was similar (2.1, 95% CI 1.2–3.5) to those previously reported (range 1.4–3.0).9,11,25 A variety of chemicals contained in cigarette smoke, including nicotine and cotinine, have been found in the cervical mucous of smokers, and it is postulated that this may produce a change in vaginal flora. However, smoking is associated with high-risk behaviors, and whether there is any true causal relationship between bacterial vaginosis and smoking remains to be established.
Several previously reported associations with bacterial vaginosis were not seen in this study or did not reach statistical significance. There was a positive association between female sexual partners and bacterial vaginosis; however, the low number of lesbians participating in the study limited our ability to detect the significant associations that have been reported by others.9,27 Sex work has been associated with bacterial vaginosis, and although there was a positive association between bacterial vaginosis and sex work in our study, the association did not reach statistical significance. Sex workers who participated in this study were predominantly legal brothel-based workers, who attend our service monthly for sexually transmitted infection screening, have low rates of bacterial sexually transmitted infections and high rates of consistent condom use (David Lee, Melbourne Sexual Health Centre, personal communication). Douching was not associated with bacterial vaginosis, but was significantly associated with candidiasis. Douching has been associated with bacterial vaginosis10,28 and with candidiasis22,29 in other studies.
Our study had a number of limitations. First, it used an observational study design (level of evidence II-2) and therefore it is not possible to rule out unmeasured confounding that may have affected the findings. In addition, the difficultly of clearly separating cases from controls (ie, classification of intermediate flora) could bias the study toward the null and may have accounted for the relatively modest odds ratios. Last, our control group is likely to have been at higher risk of sexually transmitted infections than average for the general community, which would have reduced our ability to detect significant associations. In planning this study, we decided not to use community-based controls because of the difficultly in recruiting women who would require speculum examination. In addition, we decided not to use asymptomatic women attending our service, because they have lower-risk behaviors and may artificially elevate the risks associated with bacterial vaginosis (23% of asymptomatic women attending our service during the study period had > 1 male sexual partner in the last 3 months, whereas 30% of bacterial vaginosis-negative controls had > 1 male sexual partner in the last 3 months, P = .07). We therefore decided upon a clearly defined group of women attending the center with the same specific vaginal symptoms. This meant it would be unlikely that we would overestimate risk, but this may have reduced our ability to detect significant associations. However, despite these limitations, the magnitude of the associations observed in this study is similar to that reported in other observational studies of bacterial vaginosis and candidiasis, and although modest, the odds ratios also fall within the range reported in observational studies of behavioral practices associated with sexually transmitted infections such as Chlamydia.
An association between bacterial vaginosis and sexual risk behaviors has been reported in both heterosexual and homosexual women; however, the notion that bacterial vaginosis is sexually transmitted is still debated. Commonly cited evidence against sexual transmission of bacterial vaginosis includes the failure to prevent recurrence of bacterial vaginosis in women when male sexual partners are concurrently treated. No significant benefit from partner treatment was reported in 5 of 6 trials using regimens containing metronidazole, clindamycin, or tinidazole.30 However, it is difficult to interpret these findings and to use them as evidence to refute sexual transmission in the pathogenesis of bacterial vaginosis, given the relatively high recurrence rates of bacterial vaginosis observed in women after these antibiotic regimens and the absence of a known causative organism for bacterial vaginosis. Additional commonly stated evidence against sexual transmission of bacterial vaginosis is a study that reported the occurrence of bacterial vaginosis in 6 supposedly virginal adolescents.31 It is certainly possible that the sexual risk behaviors associated with bacterial vaginosis in our and other studies may not be indirect evidence for sexual transmission of an infectious agent, but that other factors such as a disturbance in vaginal flora and in local immunity may occur as a consequence of exposure to a new sexual partner, multiple sexual partners, or from increased sexual activity. There appears, however, to be a considerable body of evidence to support sexual transmission of bacterial vaginosis between women.32 In 1955 Gardner and Dukes33 demonstrated transmission of bacterial vaginosis from affected women to unaffected women by transfer of vaginal secretions, and high concordance of bacterial vaginosis between lesbian couples27,32 and an association with insertive unwashed sex toys27 has been reported. Increased numbers of recent and past sexual partners9 have also been associated with bacterial vaginosis among lesbians. With considerable evidence to implicate sexual transmission of bacterial vaginosis between women, it is likely that the pathogenesis in the heterosexual population is similar. Although there are few studies examining bacterial vaginosis-associated organisms and their clinical sequelae in men, these organisms have been isolated from the urethra, the prepuce, and the coronal sulcus,34Gardnerella vaginalis has been reported as a cause of balanoposthitis,35 and bacterial vaginosis has been shown to be more common in female partners of men with nonspecific urethritis, and nonspecific urethritis as more common in male partners of women with bacterial vaginosis.36
While the precise cause remains unknown, the role of sexual transmission in the pathogenesis of bacterial vaginosis will remain controversial. It is unclear whether the high recurrence rates of bacterial vaginosis after treatment are due to failure to eradicate bacterial vaginosis-associated flora that are resistant to current regimens, failure to treat an as yet unidentified pathogen, reinfection from untreated sexual partners, or a combination of these factors. The recent identification of metronidazole resistant Atopobium vaginae, which appears to be uncommon in women with normal flora but present in the majority of women with bacterial vaginosis,37,38 may prove to be a significant advance in understanding the cause of bacterial vaginosis, and provides further evidence that solely imidazole-based regimens for treatment of bacterial vaginosis are unlikely eradicate infection. Ultimately, only prospective and partner studies and identification of the specific causative factor responsible for bacterial vaginosis, will be able to establish whether bacterial vaginosis is sexually transmitted. However, contrasting the factors associated with bacterial vaginosis compared with vaginal candidiasis has facilitated the identification of high-risk behaviors for bacterial vaginosis, which were not observed with candidiasis. The association between bacterial vaginosis and behaviors that are associated with sexually transmitted infections provides further evidence to support a possible sexually transmitted cause.
1. Hay PE, Lamont RF, Taylor-Robinson D, Morgan DJ, Ison C, Pearson J. Abnormal bacterial colonisation of the genital tract and subsequent preterm delivery and late miscarriage. BMJ 1994;308:295–8.
2. McGregor JA, French JI, Parker R, Draper D, Patterson E, Jones W, et al. Prevention of premature birth by screening and treatment for common genital tract infections: results of a prospective controlled evaluation. Am J Obstet Gynecol 1995;173:157–67.
3. Hillier SL, Nugent RP, Eschenbach DA, Krohn MA, Gibbs RS, Martin DH, et al. Association between bacterial vaginosis and preterm delivery of a low-birth-weight infant. The Vaginal Infections and Prematurity Study Group. N Engl J Med 1995;333:1737–42.
4. Taha TE, Hoover DR, Dallabetta GA, Kumwenda NI, Mtimavalye LA, Yang LP, et al. Bacterial vaginosis and disturbances of vaginal flora: association with increased acquisition of HIV. AIDS 1998;12:1699–706.
5. Sewankambo N, Gray RH, Wawer MJ, Paxton L, McNaim D, Wabwire-Mangen F, et al. HIV-1 infection associated with abnormal vaginal flora morphology and bacterial vaginosis [published erratum appears in Lancet 1997;350:1036]. Lancet 1997;350:546–50.
6. Amsel R, Totten PA, Spiegel CA, Chen KC, Eschenbach D, Holmes KK. Nonspecific vaginitis: diagnostic criteria and microbial and epidemiologic associations. Am J Med 1983;74:14–22.
7. Nugent RP, Krohn MA, Hillier SL. Reliability of diagnosing bacterial vaginosis is improved by a standardized method of gram stain interpretation. J Clin Microbiol 1991;29:297–301.
8. Bradshaw CS, Morton AN, Garland SM, Horvath LB, Kuzevska I, Fairley CK. An evaluation of a point-of-care test, BVBlue, and clinical and laboratory criteria for the diagnosis of bacterial vaginosis (BV). J Clin Microbiol 2005;43:1304–8.
9. Bailey JV, Farquhar C, Owen C. Bacterial vaginosis in lesbians and bisexual women. Sex Transm Dis 2004;31:691–4.
10. Schwebke JR, Desmond RA, Oh MK. Predictors of bacterial vaginosis in adolescent women who douche. Sex Transm Dis 2004;31:433–6.
11. Smart S, Singal A, Mindel A. Social and sexual risk factors for bacterial vaginosis. Sex Transm Infect 2004;80:58–62.
12. Nilsson U, Hellberg D, Shoubnikova M, Nilsson S, Mardh PA. Sexual behavior risk factors associated with bacterial vaginosis and Chlamydia trachomatis infection. Sex Transm Dis 1997;24:241–6.
13. Avonts D, Sercu M, Heyerick P, Vandermeeren I, Meheus A, Piot P. Incidence of uncomplicated genital infections in women using oral contraception or an intrauterine device: a prospective study. Sex Transm Dis 1990;17:23–9.
14. Rylander E, Berglund AL, Krassny C, Petrini B. Vulvovaginal candida in a young sexually active population: prevalence and association with oro-genital sex and frequent pain at intercourse. Sex Transm Infect 2004;80:54–7.
15. de Leon EM, Jacober SJ, Sobel JD, Foxman B. Prevalence and risk factors for vaginal Candida colonization in women with type 1 and type 2 diabetes. BMC Infect Dis 2002;2:1.
16. Geiger AM, Foxman B. Risk factors for vulvovaginal candidiasis: a case-control study among university students. Epidemiology 1996;7:182–7.
17. Mardh PA, Novikova N, Stukalova E. Colonisation of extragenital sites by Candida in women with recurrent vulvovaginal candidosis. BJOG 2003;110:934–7.
18. O'Connor MI, Sobel JD. Epidemiology of recurrent vulvovaginal candidiasis: identification and strain differentiation of Candida albicans. J Infect Dis 1986;154:358–63.
19. Calzolari E, Masciangelo R, Milite V, Verteramo R. Bacterial vaginosis and contraceptive methods. Int J Gynaecol Obstet 2000;70:341–6.
20. Schwebke JR, Richey CM, Weiss HL. Correlation of behaviors with microbiological changes in vaginal flora. J Infect Dis 1999;180:1632–6.
21. Keane FE, Ison CA, Taylor-Robinson D. A longitudinal study of the vaginal flora over a menstrual cycle. Int J STD AIDS 1997;8:489–94.
22. Barousse MM, Van Der Pol BJ, Fortenberry D, Orr D, Fidel PL Jr. Vaginal yeast colonisation, prevalence of vaginitis, and associated local immunity in adolescents. Sex Transm Infect 2004;80:48–53.
23. Shoubnikova M, Hellberg D, Nilsson S, Mardh PA. Contraceptive use in women with bacterial vaginosis. Contraception 1997;55:355–8.
24. Spinillo A, Capuzzo E, Nicola S, Baltaro F, Ferrari A, Monaco A. The impact of oral contraception on vulvovaginal candidiasis. Contraception 1995;51:293–7.
25. Hellberg D, Nilsson S, Mardh PA. Bacterial vaginosis and smoking. Int J STD AIDS 2000;11:603–6.
26. Goldenberg RL, Das A. Fetal fibronectin and bacterial vaginosis in smokers and nonsmokers. The National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Am J Obstet Gynecol 2000;182:164–6.
27. Marrazzo JM, Koutsky LA, Eschenbach DA, Agnew K, Stine K, Hillier SL. Characterization of vaginal flora and bacterial vaginosis in women who have sex with women. J Infect Dis 2002;185:1307–13.
28. Ness RB, Hillier SL, Richter HE, Soper DE, Stamm C, McGregor J, et al. Douching in relation to bacterial vaginosis, lactobacilli, and facultative bacteria in the vagina. Obstet Gynecol 2002;100:765–72.
29. Spinillo A, Pizzoli G, Colonna L, Nicola S, De Seta F, Guaschino S. Epidemiologic characteristics of women with idiopathic recurrent vulvovaginal candidiasis. Obstet Gynecol 1993;81:721–7.
30. Potter J. Should sexual partners of women with bacterial vaginosis receive treatment? Br J Gen Pract 1999;49:913–8.
31. Bump RC, Buesching WJ 3rd. Bacterial vaginosis in virginal and sexually active adolescent females: evidence against exclusive sexual transmission. Am J Obstet Gynecol 1988;158:935–9.
32. Berger BJ, Kolton S, Zenilman JM, Cummings MC, Feldman J, McCormack WM. Bacterial vaginosis in lesbians: a sexually transmitted disease. Clin Infect Dis 1995;21:1402–5.
33. Gardner HL, Dukes CD. Haemophilus vaginalis vaginitis: a newly defined specific infection previously classified non-specific vaginitis. Am J Obstet Gynecol 1955;69:962–76.
34. Serour F, Samra Z, Kushel Z, Gorenstein A, Dan M. Comparative periurethral bacteriology of uncircumcised and circumcised males. Genitourin Med 1997;73:288–90.
35. Burdge DR, Bowie WR, Chow AW. Gardnerella vaginalis-associated balanoposthitis. Sex Transm Dis 1986;13:159–62.
36. Keane FE, Thomas BJ, Whitaker L, Renton A, Taylor-Robinson D. An association between non-gonococcal urethritis and bacterial vaginosis and the implications for patients and their sexual partners. Genitourin Med 1997;73:373–7.
37. Verhelst R, Verstraelen H, Claeys G, Verschraegen G, Delanghe J, Van Simaey L, et al. Cloning of 16S rRNA genes amplified from normal and disturbed vaginal microflora suggests a strong association between Atopobium vaginae, Gardnerella vaginalis and bacterial vaginosis. BMC Microbiol 2004;4:16.
© 2005 The American College of Obstetricians and Gynecologists
38. Ferris MJ, Masztal A, Aldridge KE, Fortenberry JD, Fidel PL Jr, Martin DH. Association of Atopobium vaginae, a recently described metronidazole resistant anaerobe, with bacterial vaginosis. BMC Infect Dis 2004;4:5.