PREVALENCE OF BACTERIAL VAGINOSIS AND VAGINAL UROPATHOGENS IN POST-MENOPAUSAL WOMEN WITH AND WITHOUT ORAL HORMONE THERAPY

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1 International Journal of Medicine and Pharmaceutical Sciences (IJPMPS) ISSN Vol.2, Issue 2, Sep TJPRC Pvt. Ltd., PREVALENCE OF BACTERIAL VAGINOSIS AND VAGINAL UROPATHOGENS IN POST-MENOPAUSAL WOMEN WITH AND WITHOUT ORAL HORMONE THERAPY SRINAREE KAEWRUDEE, WANPEN UNGPINITPONG, CHUANCHOM SAKONDHAVAT, JADSADA THINKHAMROP, SUKREE SOONTRAPA & WORALUK SOMBOONPORN Department of Obstetrics and Gynecology, Faculty of Medicine, Khon Kaen University, Thailand ABSTRACT Objective: To compare the prevalences of bacterial vaginosis and vaginal uropathogens isolated from post-menopausal women taking or not taking oral hormone therapy. Material and Method: This was a cross-sectional study comprising 100 post-menopausal women who were asked to participate when they came for their annual Pap smear. Half were on oral hormone therapy and half were not. Women with the following conditions were excluded, those using any vaginal suppository drug or immunosuppressive drug, those with predisposing medical condition to vaginitis (e.g., diabetes mellitus, human immunodeficiency virus infection) or those who had had 3 or more vaginitis episodes per year. A specimen of vaginal secretion from the posterior fornix of the vagina was collected from each participant and processed for Gram s stain and cultivated to identify the targeted organisms including bacterial vaginosis and uropathogens. Results: Among the 100 post-menopausal women, the prevalence of bacterial vaginosis and vaginal uropathogens for women taking oral hormone therapy was 20% and 24%, respectively, compared to 44% and 54% for women not on oral hormone therapy. Bacterial vaginosis and vaginal uropathogens were less prevalent among hormone therapy users (p = 0.01 and 0.002, respectively). Conclusion: Post-menopausal women on hormone therapy have a lower prevalence of bacterial vaginosis and uropathogens than non-users. It is suggested that post-menopausal women not on hormone therapy be made especially aware of bacterial vaginosis and uropathogenic flora in vagina. KEYWORDS: Post-menopausal hormone therapy; Bacterial vaginosis; Vaginal uropathogens; Vaginal flora INTRODUCTION Bacterial vaginosis is the result of a replacement of the lactobacilli of the vagina through particular groups of bacteria accompanied by a characteristic change in properties of the vaginal fluid (1). More than half of women with bacterial vaginosis have no symptoms although the condition is not

2 20 Srinaree Kaewrudee & et al. entirely benign. The potential for pathogenic bacteria to be found in the vagina is high; therefore, women may be at risk of post-operative morbidity, adverse obstetric outcomes and perhaps HIV infection (2-6). It is generally accepted that lactobacilli play a major role in maintaining the urogenital health by preventing the overgrowth and invasion of pathogenic bacteria; through competition for nutrients and production of antimicrobial substances (i.e., hydrogen peroxide, organic acids, bacteriocins and biosurfactants) (7,8). Lactobacillus in the vaginal microflora is found less in post-menopausal women than in women of reproductive age (9, 10). Urinary tract infections (UTI) are among the most common bacterial infections in adults and the incidence markedly increases in older women (11, 12). Although it has been recognized that intravaginal administration of estriol prevents recurrent urinary tract infection in post-menopausal women (13, 14), the therapeutic role of oral estrogen remains unclear (15-18). As a result, this study was conducted to compare the prevalences of bacterial vaginosis and vaginal uropathogens in post-menopausal women on or not on oral hormone therapy. MATERIALS AND METHOD A cross-sectional study of 100 post-menopausal women half on (a user) and half not on (a non-user) oral hormone therapy more than 6 months was conducted after obtaining approval from Khon Kaen University s Ethics Committee for Human Research. Women attending the Menopausal Women Clinic at Srinagarind Hospital, Faculty of Medicine, Khon Kaen University, between July 2007 and March 2008, for an annual Pap smear, were asked if they would like to participate in this study. Women with the following conditions were excluded from the study: those using any vaginal suppository drug or immunosuppressive drug, those with any predisposing medical condition to vaginitis (e.g., diabetes mellitus or human immunodeficiency virus infection) or those who had had 3 or more vaginitis episodes per year. All participants were evaluated by the same attending physician; all underwent an interview to obtain demographic characteristics, duration since the last menopause, history of symptoms (which included pelvic pain, dysuria, abnormal discharge), frequency of intercourse per month in the 6 months prior to examination and vaginal douche practices. A pelvic examination was then conducted on each participant. An unlubricated speculum was inserted into the vagina. Vaginal secretion was collected from the posterior fornix of vagina with two sterile cotton-tipped swabs. One swab was smeared onto a glass slide for Gram s stain evaluation according to the Nugent scoring system (19, 20). The second swab was placed in a transport vial and sent to the microbiology laboratory for cultivation, to identify the uropathogens and to confirm bacterial vaginosis. The laboratory staff was not apprised of the participants demographic characteristics or hormone-therapy-using status.

3 Prevalence of Bacterial Vaginosis and Vaginal Uropathogens in Post-Menopausal 21 Women with and Without Oral Hormone Therapy The Nugent scoring system is a standardized point scoring system (0 to 10) based on the presence of 3 bacterial morphotypes: large gram positive rods (Lactobacillus spp); small gram-negative or gram-variable coccobacilli (Gardnerella and anaerobic spp); and, curved gram-variable rods (Mobiluncus spp). A Nugent score of 0 to 3 is classed as normal flora, 4 to 6 as intermediate flora, and 7 to 10 as bacterial vaginosis. Variable Table 1. Demographic Characteristics of Participants All participants (N=100) User (N=50) Non-user (N=50) P-value Age ±SD (years) 55.18± ± ± Previous births Menopause duration ±SD (years) 7.97± ± ± Number of sexual intercourse/month (last 6 months) > Vaginal douche practice STATISTICAL ANALYSIS Descriptive statistics, including mean and standard deviation (SD), were calculated for all of the continuous variables, while frequencies were generated for the discrete variables. SPSS Version was used to analyze the data. The p-value required for statistical significance was 0.05 or less. A Chisquare test was used to assess the difference in prevalence of bacterial vaginosis and uropathogens for each hormone and non-hormone using group. The continuous variables for each group were compared using the Student t test. RESULTS Each group consisted of 50 women, half were taking and half were not taking hormone therapy. The mean age and duration from menopause of the participants was 55 and 7.9 years, respectively. The demographic characteristics of participants are presented in Table 1. After categorizing the participants

4 22 Srinaree Kaewrudee & et al. into the hormone or non-hormone using group, we found no statistically significant difference in terms of mean age, previous births, duration from menopause, frequency of intercourse or vaginal douche practice between the two groups. Table 2 presents the number of women by type of hormonal regimen: estradiol valerate combined with medroxy progesterone acetate (MPA) was used by more than half of the participants followed by Tibolone. Table 2. Number of women by type of hormone therapy Type of hormone therapy No. of women (N=50) % Estradiol valerate/mpa Tibolone beta Estradiol/ Norethisterone 2 4 Conjugated estrogens MPA beta Estradiol/Drospirenone 2 4 Total After the Gram stained slides were evaluated using the Nugent scoring system, bacterial vaginosis was diagnosed in 32 participants. Ten (20%) of them were in the users group and 22 (44%) were in the non-users group. This difference was statistically significant (p = 0.01). Table 4 shows the frequency of isolating microbes from the vaginal secretion, stratified by the user group. All vaginal swabs from which Lactobacilli was isolated had only a single microbe cultivated, while others where Lactobacilli were not isolated had 0-4 microbes per sample. Uropathogens (Escherichia coli, Enterococcal species, Pseudomonas aeruginosa and Klebsiella pneumoniae) were less common in 12 (24%) women taking oral hormone therapy compared to 27 (54%) women not taking hormone therapy (p < 0.01). Table 3. Prevalence of bacterial vaginosis & uropathogens in the oral hormone-therapy-users group vs. the non-users group Hormone Users Non-users p-value Bacterial vaginosis 20% 44% 0.01 Vaginal uropathogens 24% 54% 0.002

5 Prevalence of Bacterial Vaginosis and Vaginal Uropathogens in Post-Menopausal 23 Women with and Without Oral Hormone Therapy Table 4. Frequency of Isolating Microbes From the Vaginal Secretion Within Groups of Women Taking (User) Vs. Not Taking (Non-User) Oral Hormone Therapy Micro-organisms Hormone User non-user P-value No growth Streptococcus spp Staphylococcus spp Escherichia coli Enterococcus spp Lactobacillus spp Gardnerella vaginalis Corynebacterium Candida species 9 1 <0.01 Pseudomonas aeruginosa Klebsiella pneumoniae * More than one organism was identified in a vaginal secretion sample. DISCUSSIONS The study was conducted among healthy post-menopausal women in whom the prevalence of bacterial vaginosis according to the Nugent scoring in women with oral hormone therapy vs. nonusers was 20 vs. 44 percent. This confirms two previous studies (21, 22) regarding the significant protective action of hormone therapy against the presence of microbes associated with bacterial vaginosis, but differs from one study in Italy (10) in which the prevalence of bacterial vaginosis (using a modified Nugent s criteria) was 6% overall for post-menopausal women (5.4% of hormone users and 6.3% of nonusers). Although a previous study among asymptomatic young women found a lower prevalence of bacterial vaginosis among Asian/Pacific Islanders than other ethnic groups (23), the result of our study was that the prevalence among Thai post-menopausal women was similar to previous studies (21, 24) in western countries.

6 24 Srinaree Kaewrudee & et al. Urinary tract infections represent an important health problem for post-menopausal women. The main causative uropathogens in elderly women are E. coli, Proteus species, Enterococci, K. pneumoniae and P. aeruginosa, all of which, except the last one, are Enterobacteriacae. The use of topical estrogen was associated with a significant increase in the rate of vaginal colonization with lactobacilli, and in the rate of vaginal colonization with Enterobacteriacae. Intravaginal administration of estrogen prevented recurrent UTI in post-menopausal women (13, 14). The prevalence figures for uropathogens, lower in oral hormone users than non-users, confirms the previous findings from a similar population (21) and, furthermore, our study showed that when Lactobacilli species colonize the vagina, no pathogen coexists. Although oral hormone therapy increased Lactobacilli, and reduced uropathogens in vagina, an animal experimental study found that (1) estrogen enhanced E. coli adherence to epithelial cells (25) and (2) significantly increased the susceptibility of surgically menopausal mice to ascending UTI (18). Data from a randomized, blinded trial of the effects of hormone therapy on coronary heart disease events among post-menopausal women, with established coronary heart disease, demonstrated oral hormone therapy did not reduce the frequency of urinary tract infections. Therefore, the role of hormone therapy on UTI remains unclear. Vaginal colonization with uropathogens, however, does not inevitably lead to UTI. It remains to be determined why vaginal colonization progresses to UTI in some women (26) and not in others. According to 2005 guidelines from the Infectious Diseases Society of America, the diagnosis and treatment of asymptomatic bacteriuria in adults, the treatment of asymptomatic bacteriuria in older women living in a community setting is not recommended (27). Before our results can be implemented for clinical use, one must consider that the population in this study was based on a convenient sample of consecutive women at a menopausal women clinic who met the inclusion criteria until the sample size was complete. The limitation of this type of sampling is that it might lead to a selection bias. A prospective, placebo-controlled study is needed to obtain evidence of possible benefits. If our results are substantiated by further research, non-user postmenopausal women might be made aware of the potential for bacterial vaginosis and uropathogens in the vagina. ACKNOWLEDGEMENTS The authors thank: (1) the staff of the Menopausal Women Clinic for their assistance with recruitment; (2) the microbiology laboratory personnel for doing the Gram s stain and cultivation; (3) Associate Dr. Kanok Seejorn, Head of the Department of Obstetrics and Gynecology, for his permission to conduct the present study, (4) Research Affairs, Faculty of Medicine, Khon Kaen University for funding support; and, (5) and Mr. Bryan Roderick Hamman for assistance with the English-language presentation of the manuscript.

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