| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
ORIGINAL RESEARCH |
From the Divisions of 1Obstetrics and Gynecology and 2Clinical Chemistry, Danderyd Hospital, Stockholm, Sweden.
 |
ABSTRACT |
|---|
TOP
 ABSTRACT MATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
METHODS: Thirty-eight women with recurrent vulvovaginal candidiasis and 45 healthy, age-matched controls completed a health questionnaire regarding general and gynecologic health and food and alcohol habits. They all underwent an oral glucose tolerance test and a vaginal examination. Vaginal secretion was collected from the proximal part of the vagina. Glucose in plasma and in vaginal secretions were measured at fasting and after 2 hours and analyzed with the hexokinase method. A sample size analysis showed that the number of subjects included in the study was sufficient for a ß value of 0.80, at the significance level of 
=.05, at a difference in glucose in vaginal secretions of 30 % after oral glucose tolerance test.
RESULTS: In healthy women, the median level of glucose in vaginal secretions was 5.2 mM before and 3.7 mM after oral glucose tolerance test, and plasma glucose was 5.0 mM before and 5.8 mM after oral glucose tolerance test. No significant difference was seen regarding change of glucose level in vaginal secretions and plasma glucose after testing, compared with before oral glucose tolerance testing.
CONCLUSION: There were no differences between women with recurrent vulvovaginal candidiasis and control subjects regarding change in glucose level in vaginal secretions or in plasma during oral glucose tolerance test.
LEVEL OF EVIDENCE: II-2
Women with recurrent vulvovaginal candidiasis suffer from vulvar dryness, cracks, and soreness that often cause dyspareunia, which may have a severe effect on the relationship and the quality of life. Some of these women may develop localized provoked vestibulodynia—a chronic disorder characterized by erythematous, painful mucosa of the vestibulum vulvae, which makes sexual intercourse virtually impossible.4,5 Seventy-five percent of women who suffer from localized provoked vestibulodynia report a history of recurrent vulvovaginal candidiasis.6 The incidence of localized provoked vestibulodynia is increasing.6
Many factors have been discussed concerning the pathogenesis of recurrent vulvovaginal candidiasis, for instance poorly regulated diabetes,7 pregnancy,1,8 long-term treatment with corticosteroids or chemostatics,1,8 immunologic factors,9 and oral contraceptives.10,11 The use of intrauterine device,8 frequent sexual intercourse,8 several sexual partners,8 and oral sex12 have also been suspected to increase the risk for developing recurrent vulvovaginal candidiasis. In a recent study, we have shown that chronic stress may play a role in the pathogenesis of recurrent vulvovaginal candidiasis.13
Because poorly controlled diabetes mellitus is a known risk factor for developing recurrent vulvovaginal Candida infections,7 there is a belief that dietary factors such as excessive intake of carbohydrates or sweets might increase the risk of recurrent vulvovaginal candidiasis. However, there are few scientific reports concerning this topic. According to one study, women with recurrent vulvovaginal candidiasis have elevated urinary secretion of glucose.14 Recently, results were presented that showed slightly impaired glucose tolerance in women with recurrent vulvovaginal candidiasis.15 However, levels of glucose in vaginal secretions have not previously been measured (PubMed July 2006, search words: glucose, vagina, vaginal secretion, vaginal physiology, recurrent vulvovaginal candidiasis; all languages).
The aim of this study was to present a method to measure vaginal secretion of glucose and to evaluate the levels of glucose in vaginal secretions and plasma glucose before and after an oral glucose tolerance test in women with recurrent vulvovaginal candidiasis and in healthy control subjects.
|
MATERIALS AND METHODS |
|---|
|
TOP
ABSTRACTMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
The control group consisted of healthy medical students and other healthy subjects, recruited by advertising in a local newspaper. Fourteen patients and 17 controls were using the oral contraceptive pill (OCP), and 24 patients and 28 control subjects did not use OCP. The women not using OCP were studied during days 5–11 of the menstrual cycle. We wished to analyze glucose in the preovulatory phase when there is estrogen but no progesterone production in the ovaries. The women were asked to avoid sexual intercourse for 24 hours before the examination.
All women underwent a careful vulvovaginal examination. Vaginal samples for fungal culture were collected by cotton swabs, and subsequently plated on CHROM-agar and glucose blood agar. A vaginal wet amount for microscopy was also obtained, to eliminate current cervicitis and vaginal infections other than Candida. The microscopic criteria used to exclude cervicitis or vaginal infections other than Candida were a wet smear without dominance of leukocytes or cocci, lack of clue cells or Trichomonas vaginalis, and lactobacilli present. Urinary glucose was analyzed with Multistix 10 SG (Bayer Diagnostics Ltd., Tarrytown, NY) reagent strip for urinanalysis
The women completed a questionnaire regarding current and previous general and gynecologic health. Daily intake of vegetables and dairy products, as well as alcohol habits per week was registered. Blood samples were obtained for analysis of serum hemoglobin A1C(Hb A1C).
An oral glucose tolerance test was performed in all women. Plasma glucose was measured once in the morning at fasting and once 2 hours after intake of 75 g of glucose, according to the standard procedure for oral glucose tolerance test in clinical praxis in Sweden. Vaginal fluid was collected on a sterile, weighed strip of filter paper once at fasting and once 2 hours after intake of 75 g of glucose. The filter paper was inserted in the posterior fornix and kept there for three minutes. It was then placed in a weighed sample tube containing 20 mg of sodium fluoride and 143 international units of Na2-EDTA (BD Vacutainer Systems, Plymouth, UK) to which 500 mcL 0.9% NaCl had been added. The tube containing the strip of filter paper soaked in vaginal fluid was reweighed to determine the weight of the sample obtained. After mixing by tube inversions (10 minutes) and centrifugation (10 minutes, 3,000g) the supernatant was collected. The hexokinase method (Gluco-quant, Modular Analytics, Roche Diagnostics, Mannheim, Germany) was used for analysis of glucose. The obtained results were adjusted according to sample weight and dilution. The precision of this procedure was evaluated as follows: Twenty-two pieces of filter paper were soaked in plasma and inserted in the 22 sample tubes as described above. The concentration of glucose was determined in the supernatants and adjusted for dilution. The coefficient of variation from 22 measurements was less than 3% for glucose (range 5.06–5.83 mM). Direct measurements of glucose (5.22 and 5.18 mM) in the same plasma sample gave results within the respective ranges.
The local Ethics Committee of the Karolinska hospital approved the study. Participation was voluntary and kept anonymous. The women provided written informed consent for participation in the study.
A sample size calculation was performed, indicating that 2x40 subjects would be sufficient to detect a difference in vaginal glucose (2-hour values) change of 30% (50% compared with 80%) (power 80% and significance level 5%, two-tailed hypothesis).
Fifty percent of the controls were supposed to show higher glucose values after oral glucose tolerance test as compared with before oral glucose tolerance test. Correspondingly, 80% of the patients were supposed to do the same.
The first aim of this study was to analyze v-glucose change before and after oral glucose tolerance test between cases and controls and to take possible confounders into consideration. The choice of statistical methods was thus independent tests between groups (Mann Whitney U test and t test) and analysis of variance in the multivariate tests. Box plot was used to illustrate the comparisons.
|
RESULTS |
|---|
|
TOP
ABSTRACTMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
|
In healthy women, the median level of glucose in vaginal secretions was 5.2 mM before and 3.7 mM after oral glucose tolerance test, and plasma glucose was 5.0 mM before and 5.8 mM after oral glucose tolerance test. The interindividual levels varied between 0.2 and 149.0 mM. Urinary glucose was analyzed in 52 women (21 patients, 31 controls). None of the women had detectable levels of urinary glucose.
When comparing cases (n=38) and controls (n=45), no significant differences were seen regarding change in paired comparisons of vaginal or plasma glucose at fasting and 2 hours after oral glucose tolerance test (Table 2 and Table 3), (Fig. 1A and B). Moreover, the vaginal-to-plasma ratio 2 hours after oral glucose tolerance test or Hb A (Fig. 1C and D) did not differ between the groups.
|
|
|
There were no differences in paired comparisons between women with (n=52) and without OCP (n=31), either in vaginal or in plasma glucose before and after oral glucose tolerance test (Table 2). Women with OCP (mean age 25.8, SD ±5.0 years) were younger than women not using OCP (mean age 28.8, SD ±5.2 years) (P<.05).
The exclusion of seven patients and three controls with vaginal growth of bacteria or fungi did not change the results in any of the analyses. Neither were there any differences concerning the above-mentioned variables when comparing cases using OCP (n=14) and controls not using OCP (n=28), nor in 11 women with growth compared with 40 controls without growth.
One woman with insulin-dependent diabetes mellitus was analyzed. Although the plasma level of glucose was 14.3 mM, the level in vaginal secretions was only 0.62 mM.
|
DISCUSSION |
|---|
|
TOP
ABSTRACTMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
In this study, a method to measure glucose levels in the vagina is presented. A similar procedure to collect vaginal fluid has been described in measuring penicillin and cotinine.16,17 It is conceivable that measuring the glucose level 2 hours after intake of 75 g of glucose is representative of the dietary situation.
With the described technique of sampling vaginal secretions, no differences in change of glucose levels during oral glucose tolerance test were found between women with recurrent vulvovaginal candidiasis and control subjects. Our results concerning plasma glucose are not in accordance with observations by Donders et al,15 who found that women with recurrent vulvovaginal candidiasis had a slightly impaired glucose tolerance, compared with the controls. However, in the study by Donders et al, the patients were older and had a higher body mass index than the control subjects, which might influence the results. Horowitz et al14 found elevated levels of urinary sugar in women with ongoing Candida infection and Darwazeh et al18 observed that diabetic women who were orally colonized with Candida had higher oral glucose levels than diabetics and healthy control women without oral Candida. In our study, however, glucose in vaginal secretions was not elevated in women with growth of Candida. One reason for the observed interindividual variation in glucose levels might be the influence of glycolysis from glycogen stored in the vaginal epithelial cells.19
Women using OCP have been shown to have elevated levels of plasma glucose and Hb A1C. In addition, women with OCP suffer from recurrent vulvovaginal candidiasis more often than women not using OCP.10 However, in our sample, the glucose in vaginal secretions was not higher in women with OCP than in healthy women or women with recurrent vulvovaginal candidiasis. Nor was there any difference between patients with OCP and healthy women not using OCP.
Pregnant women, insulin-dependent diabetics and women with immunosuppressive treatment do easily get vulvovaginal candidiasis. An impaired local immune system might be a pathogenic factor in common in these disorders. Both in pregnancy and during insulin-dependent diabetes, the mucosal immune functioning is impaired.20 It has been proposed that the innate part of the local immune system of the vagina is involved in the pathogenesis of recurrent vulvovaginal candidiasis.21,22 In conclusion, our results do not support the hypothesis that high intake of carbohydrates will affect the pathogenesis of recurrent vulvovaginal candidiasis, and thus a carbohydrate-free diet cannot be recommended as a prophylactic treatment.
|
Footnotes |
|---|
doi:10.1097/01.AOG.0000246800.38892.fc
|
REFERENCES |
|---|
|
TOP
ABSTRACTMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
2. Mardh PA, Rodrigues AG, Genc M, Novikova N, Martinez-de-Oliveira J, Guaschino S. Facts and myths on recurrent vulvovaginal candidosis—review on epidemiology, clinical manifestations, diagnosis, pathogenesis and therapy. Int J STD AIDS 2002;13:522–39.[Medline]
3. Mardh PA, Wagstrom J, Landgren M, Holmen J. Usage of antifungal drugs for therapy of genital Candida infections, purchased as over-the-counter products or by prescription: 2. Factors that may have influenced the marked changes in sales volumes during the 1990s. Infect Dis Obstet Gynecol 2004;12:99–108.[Medline]
4. Friedrich EG Jr. Vulvar vestibulitis syndrome. J Reprod Med 1987;32:110–4.[Medline]
5. Baggish MS, Miklos JR. Vulvar pain syndrome: a review. Obstet Gynecol Surv 1995;50:618–26.[Medline]
6. Bohm Starke N, Rylander E. Vulvar vestibulitis is a condition with diffuse etiology [in Swedish]. Lakartidningen 2000;97:4832–6.[Medline]
7. Reed BD, Slattery ML, French TK. The association between dietary intake and reported history of Candida vulvovaginitis. J Fam Pract 1989;29:509–15.[Medline]
8. Reed BD. Risk factors for Candida vulvovaginitis. Obstet Gynecol Surv 1992;47:551–60.[Medline]
9. Fidel PL Jr. Vaginal candidiasis: review and role of local mucosal immunity. AIDS Patient Care STDS 1998;12:359–66.[Medline]
10. 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.[Medline]
11. Schmidt A, Noldechen CF, Mendling W, Hatzmann W, Wolff MH. Oral contraceptive use and vaginal candida colonization [in German]. Zentralbl Gynakol 1997;119:545–9.[Medline]
12. Rylander E, Berglund A-L, 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.
13. Ehrström SM, Kornfeld D, Thuresson J, Rylander E. Signs of chronic stress in women with recurrent candida vulvovaginitis. Am J Obstet Gynecol 2005;4:1376–81.
14. Horowitz BJ, Edelstein SW, Lippman L. Sugar chromatography studies in recurrent Candida vulvovaginitis. J Reprod Med 1984;29:441–3.[Medline]
15. Donders GG, Prenen H, Verbeke G, Reybrouck R. Impaired tolerance for glucose in women with recurrent vaginal candidiasis. Am J Obstet Gynecol 2002;187:989–93.[Medline]
16. Sjoberg I, Hakansson S, Holm SE. Accumulation of penicillin in vaginal fluid. Obstet Gynecol 1990;75:18–21.
17. Sasson IM, Haley NJ, Hoffmann D, Wynder EL, Hellberg D, Nilsson S. Cigarette smoking and neoplasia of the uterine cervix: smoke constituents in cervical mucus. N Engl J Med 1985;312:315–6.[Medline]
18. Darwazeh AM, MacFarlane TW, MacCuish A, Lamey PJ. Mixed salivary glucose levels and candidal carriage in patients with diabetes mellitus. J Oral Pathol Med 1991;20:280–3.[Medline]
19. Miller L, Patton DL, Meier A, Thwin SS, Hooton TM, Eschenbach DA. Depomedroxyprogesterone-induced hypoestrogenism and changes in vaginal flora and epithelium. Obstet Gynecol 2000;96:431–9.
20. Scott FW, Rowsell P, Wang GS, Burghardt K, Kolb H, Flohe S. Oral exposure to diabetes-promoting food or immunomodulators in neonates alters gut cytokines and diabetes. Diabetes 2002;51:73–8.
21. Fidel PL Jr. Immunity in vaginal candidiasis. Curr Opin Infect Dis 2005;18:107–11.[Medline]
22. Barousse MM, Steele C, Dunkap K, Espinosa T, Boikov D, Sobel JD, et al. Growth inhibition of Candida albicans by human vaginal epithelial cells. J Infect Dis 2001;184:1489–93.[Medline]
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
