This randomized double-blind placebo controlled study assessed the vaginal colonization of lactic acid bacteria and clinical outcome. Vaginal capsules containing L gasseri LN40, Lactobacillus fermentum LN99, L. casei subsp. rhamnosus LN113 and P. acidilactici LN23, or placebos were administered for five days to 95 women after conventional treatment of bacterial vaginosis and/or vulvovaginal candidiasis. Vulvovaginal examinations and vaginal samplings were performed before and after administration, after the first and second menstruation, and after six months. Presence of LN strains was assessed using RAPD analysis. LN strains were present 2-3 days after administration in 89% of the women receiving LN strains (placebo: 0%, p < 0.0001). After one menstruation 53% were colonized by at least one LN strain. Nine percent were still colonized six months after administration. Ninety-three percent of the women receiving LN strains were cured 2-3 days after administration (placebo: 83%), and 78% after one menstruation (placebo: 71%) (ns). The intervention group experienced less malodorous discharge 2-3 days after administration (p = 0.03) and after the second menstruation (p = 0.04), compared with placebo. In summary, five days of vaginal administration of LN strains after conventional treatment of bacterial vaginosis and/or vulvovaginal candidiasis lead to vaginal colonization, somewhat fewer recurrences and less malodorous discharge.

Human papillomavirus (HPV)‐based management of women with borderline atypical squamous cells of undetermined significance (ASCUS) or mildly abnormal cervical intraepithelial neoplasia (CINI) cervical cytology has been extensively studied in the research setting. We wished to assess safety and health care resource use of a real‐life health care policy using HPV triaging. All 15 outpatient clinics involved in the organized population‐based screening program in Stockholm, Sweden screening program were randomized to either continue with prior policy (colposcopy of all women with ASCUS/CINI) or to implement a policy with HPV triaging and colposcopy only of HPV‐positive women. The trial enrolled the 3,319 women who were diagnosed with ASCUS (n = 1,335) or CINI (n = 1,984) in Stockholm during 17th March 2003 to 16th January 2006. Detection of high‐grade cervical lesions (CINII+) and health care cost consumption was studied by registry linkages. The proportion of histopathology‐verified CINII+ was similar for the two policies (395 of 1,752 women (22.5%; 95% Confidence interval [CI]: 20.6–24.6%) had CINII+ diagnosed with HPV triaging policy, 318 of 1,567 women (20.3%; 95%CI: 18.3–22.4%) had CINII+ with colposcopy policy). Sixty‐four percent of women with ASCUS and 77% of women with CINI were HPV positive. HPV‐positivity was age‐dependent, with 81% of women below 35 years of age and 44% of women above 45 years of age testing HPV‐positive. HPV triaging was cost‐effective only above 35 years of age. In conclusion, a real‐life randomized healthservices study of HPV triaging of women with ASCUS/CINI demonstrated similar detection of CINII+ as colposcopy of all women.

BACKGROUND:Primary cervical screening with both human papillomavirus (HPV) DNA testing and cytological examination of cervical cells with a Pap test (cytology) has been evaluated in randomized clinical trials. Because the vast majority of women with positive cytology are also HPV DNA positive, screening strategies that use HPV DNA testing as the primary screening test may be more effective.METHODS:We used the database from the intervention arm (n = 6,257 women) of a population-based randomized trial of double screening with cytology and HPV DNA testing to evaluate the efficacy of 11 possible cervical screening strategies that are based on HPV DNA testing alone, cytology alone, and HPV DNA testing combined with cytology among women aged 32-38 years. The main outcome measures were sensitivity for detection of cervical intraepithelial neoplasia grade 3 or worse (CIN3+) within 6 months of enrollment or at colposcopy for women with a persistent type-specific HPV infection and the number of screening tests and positive predictive value (PPV) for each screening strategy. All statistical tests were two-sided.RESULTS:Compared with screening by cytology alone, double testing with cytology and for type-specific HPV persistence resulted in a 35% (95% confidence interval [CI] = 15% to 60%) increase in sensitivity to detect CIN3+, without a statistically significant reduction in the PPV (relative PPV = 0.76, 95% CI = 0.52 to 1.10), but with more than twice as many screening tests needed. Several strategies that incorporated screening for high-risk HPV subtypes were explored, but they resulted in reduced PPV compared with cytology. Compared with cytology, primary screening with HPV DNA testing followed by cytological triage and repeat HPV DNA testing of HPV DNA-positive women with normal cytology increased the CIN3+ sensitivity by 30% (95% CI = 9% to 54%), maintained a high PPV (relative PPV = 0.87, 95% CI = 0.60 to 1.26), and resulted in a mere 12% increase in the number of screening tests (from 6,257 to 7,019 tests).CONCLUSIONS:Primary HPV DNA-based screening with cytology triage and repeat HPV DNA testing of cytology-negative women appears to be the most feasible cervical screening strategy.

BACKGROUND:Localised provoked vulvodynia (former vulvar vestibulitis syndrome) is the most common cause of superficial dyspareunia among young women. In a clinical setting, it is obvious that many women with localised provoked vulvodynia show signs of chronic stress. The objective of this study was to compare chronic stress in a group of women with localised provoked vulvodynia, referred to the vulvar unit at the Division of Obstetrics and Gynecology, Danderyd Hospital, Stockholm, Sweden with control women of the same age and educational level, using two independent methods.METHODS:Forty-three women with localised provoked vulvodynia and 35 healthy control women underwent a gynecological examination, filled in a health questionnaire, and self-collected saliva for analysis of cortisol at awakening and after 15, 30 and 45 min (morning awakening cortisol). Thirty-three patients and 28 controls completed a stress questionnaire.RESULTS:Morning awakening cortisol was blunted in women with localised provoked vulvodynia (p < 0.05), indicating chronic stress. The stress questionnaire showed more signs of burnout (p < 0.005), and emotional (p < 0.05) and bodily symptoms of stress (p < 0.005) in women with localised provoked vulvodynia compared with control subjects (students t-test).CONCLUSION:More women with localised provoked vulvodynia showed blunted morning awakening cortisol and reported more symptoms of stress compared with healthy control women of the same age.

OBJECTIVE:To evaluate the long-term results of vestibulectomy in women with localized, provoked vestibulodynia.STUDY DESIGN:A retrospective questionnaire survey was filled out by 67 Swedish women who underwent surgery for localized, provoked vestibulodynia during 1992-2003. The questionnaire was completed a minimum of 12 months after the operation. Coital pain, quality of sexual life and psychologic well-being were evaluated.RESULTS:The mean age at the time of surgery was 27 years (18-56) and the median follow-up time 41 months (12-120). Coital pain, rated with Visual Analogue Scales (VAS(neg)) (0-10), was 8.0 (median) before surgery, 5.0 (p < 0.001) 6 months after surgery and 2.0 (p < 0.001) at follow-up. Quality of sexual life, using VAS(pos) (10-0), was 6.5 (median) before dyspareunia, 0.5 (p < 0.001) prior to surgery and 6.5 (p < 0.001) at followup. Complete or major improvement was reported by 56% of women with secondary vestibulodynia and 17% of women with primary vestibulodynia (p = 0.03). Improved psychologic well-being was reported by 79%.CONCLUSION:Women with secondary localized provoked vestibulodynia will often benefit from surgery when other treatments fail. Surgical outcome should include both pain relief and psychosexual well-being. In this study women with primary vestibulodynia were less likely to benefit from surgery.

Screening for cervical cancer by testing for human papillomavirus (HPV), the major cause of the disease, reportedly increases the sensitivity of detecting high-grade (grade 2 or 3) cervical intraepithelial neoplasia (CIN). It is not clear, however, whether this reflects protection against future high-grade CIN or cervical cancer, or whether it represents over-diagnosis. This Swedish population-based screening program randomly assigned 12,527 women ranging in age from 32 to 38 years to have either an HPV test plus a Pap test (n = 6257, the intervention group) or a Pap test alone (n = 6270, the control group). Those having a positive HPV test and a normal Pap test were offered a second HPV test at least 1 year later, and those persistently infected with the same high-risk type of HPV were offered colposcopy with cervical biopsy. A similar number of double-blinded Pap smears and colposcopies with biopsy were done in randomly selected control women to avoid ascertainment bias. The average follow-up interval was 4.1 years. Initially, 51% more women in the intervention group than in the control group had grade 2 or 3 CIN or cancer. On subsequent screening, the proportion of women in the intervention group who had grade 2/3 lesions or cancer was 42% less, and the proportion with grade 3 lesions or cancer was 47% less than the proportion of control women having such lesions. The increased incidence of grade 2 lesions found at initial screening in the intervention group was not followed by a significant reduction of such lesions at later screening. Women with persistent HPV infection remained at high risk of grade 2 or 3 lesions or cancer after being referred for colposcopy. Five women in the control group and one in the intervention group were found to have invasive squamous-cell carcinoma. Four in each group developed adenocarcinoma in situ or adenocarcinoma. All of these women with advanced changes were HPV-positive at baseline. The improved sensitivity of HPV testing in women in their mid-30s who are screened for cervical cancer is not solely a result of over-diagnosis. It can be ascribed-at least in part-to the earlier diagnosis of cervical lesions that do not regress on follow-up screening.

OBJECTIVE:This study was undertaken to survey the steroid receptor expression and morphology in the vulvar vestibular mucosa in women with provoked vestibulodynia.STUDY DESIGN:Fourteen patients and 25 controls without oral contraceptives were included. Vestibular biopsy specimens were obtained and analyzed by using immunohistochemistry, followed by computerized image analysis of estrogen receptors alpha and beta, progesterone receptors A and B, glucocorticoid receptor, androgen receptor, and the proliferation marker Ki67. The morphology was estimated by measuring 4 parameters in the epithelium.RESULTS:There was a significantly higher expression of estrogen receptor alpha in both the epithelium (P = .04) and the stroma (P = .02) in the patient specimens compared with the controls. There were no significant differences in the other analyses performed.CONCLUSION:There is an increased expression of estrogen receptor alpha in the vestibular mucosa but the epithelial morphology seems unaffected in women with provoked vestibulodynia. Further studies regarding plausible associations to neurogenic inflammation are needed.

BACKGROUND:An erythematous and hypersensitive vestibular mucosa has been observed during the use of combined oral contraceptives (COC). Hormonal effects on the vestibular morphology have not been studied.OBJECTIVES:Our aim was to evaluate the morphology of the vulval vestibular mucosa during the influence of COC and during the menstrual cycle.METHODS:Forty-five healthy women (20 using COC and 25 not using COC) were included. A 6-mm punch biopsy was obtained from the right posterior vestibule on days 7-11 of the menstrual cycle. A corresponding biopsy was taken 2 weeks later in 16 women without COC. The epithelial morphology was estimated by measuring interdermal papilla distance, dermal papilla to surface, from basal layer to surface and width of dermal papillae. A histopathological assessment was made.RESULTS:The vulval vestibular mucosa of women using COC displayed a larger distance between the dermal papillae (P = 0.04) and a larger space from the dermal papillae to the epithelial surface (P = 0.03) compared with controls in the follicular phase. Women without COC displayed a larger interdermal papilla distance in the luteal phase compared with the follicular phase, P = 0.02. Histopathology showed more superficial blood vessels in the COC users (P < 0.01).CONCLUSIONS:The vulval vestibular mucosa of women with COC display an altered morphological pattern with shallow and sparse dermal papillae compared with the follicular phase. Similar findings are seen in women without COC during the luteal phase which indicate a gestagenic effect on the mucosa. Associations between the morphological pattern and changes in mucosal mechanical sensitivity require further studies.

BACKGROUND Screening for cervical cancer based on testing for human papillomavirus (HPV) increases the sensitivity of detection of high-grade (grade 2 or 3) cervical intraepithelial neoplasia, but whether this gain represents overdiagnosis or protection against future high-grade cervical epithelial neoplasia or cervical cancer is unknown. METHODS In a population-based screening program in Sweden, 12,527 women 32 to 38 years of age were randomly assigned at a 1:1 ratio to have an HPV test plus a Papanicolaou (Pap) test (intervention group) or a Pap test alone (control group). Women with a positive HPV test and a normal Pap test result were offered a second HPV test at least 1 year later, and those who were found to be persistently infected with the same high-risk type of HPV were then offered colposcopy with cervical biopsy. A similar number of double-blinded Pap smears and colposcopies with biopsy were performed in randomly selected women in the control group. Comprehensive registry data were used to follow the women for a mean of 4.1 years. The relative rates of grade 2 or 3 cervical intraepithelial neoplasia or cancer detected at enrollment and at subsequent screening examinations were calculated. RESULTS At enrollment, the proportion of women in the intervention group who were found to have lesions of grade 2 or 3 cervical intraepithelial neoplasia or cancer was 51% greater (95% confidence interval [CI], 13 to 102) than the proportion of women in the control group who were found to have such lesions. At subsequent screening examinations, the proportion of women in the intervention group who were found to have grade 2 or 3 lesions or cancer was 42% less (95% CI, 4 to 64) and the proportion with grade 3 lesions or cancer was 47% less (95% CI, 2 to 71) than the proportions of control women who were found to have such lesions. Women with persistent HPV infection remained at high risk for grade 2 or 3 lesions or cancer after referral for colposcopy. CONCLUSIONS The addition of an HPV test to the Pap test to screen women in their mid-30s for cervical cancer reduces the incidence of grade 2 or 3 cervical intraepithelial neoplasia or cancer detected by subsequent screening examinations. (ClinicalTrials.gov number, NCT00479375 [ClinicalTrials.gov].).

Objective. Recurrent vulvovaginal candidiasis (RVVC) has become very common. The aim of this study was to evaluate if women with RVVC perceive more signs of chronic stress than healthy control subjects. Study design. Thirty-three women with RVVC and 28 healthy control subjects completed a questionnaire about perceived stress at work and in private life, and a health questionnaire. A comparison of the results was performed with the one-way ANOVA test. Results. More women with RVVC than control subjects reported signs of burnout (p < 0.001), emotional symptoms of stress (p < 0.005), impaired balance between work and leisure time (p = 0.01), bodily symptoms of stress (p < 0.05), worrying factors at work (p < 0.05), and presented type D-personality (p < 0.05). Conclusions. The results of this pilot study showed higher degree of perceived stress in women with RVVC compared with healthy controls. These results are in line with our earlier findings of blunted morning rise cortisol and lower mean levels of cortisol in women with RVVC compared with healthy controls.

Background: The objective was to evaluate the influence of combined oral contraceptives (COC) and of the menstrual cycle on the steroid receptor expression in the vulvar vestibular mucosa of healthy women.Study Design: Forty-five healthy women (20 with COC and 25 without) were included. Vestibular biopsies were obtained during the menstrual cycle. Estrogen receptors (ER) alpha and beta, progesterone receptors (PR) A and 13, glucocorticoid receptor and androgen receptor as well as the proliferation marker Ki67 were analyzed using immunohistochemistry followed by computerized image analysis.Results: The vestibular stromal tissue of women using COC expressed more ER beta (p=.024) than that of women without COC. In the follicular phase, PRB was more abundant in the stromal tissue than in the luteal phase (p=.01).Conclusions: ER beta is more abundant in the vulvar vestibular mucosa of women using COC than in that of women without COC. There is a cyclic variation in PRB in the vestibular mucosa in healthy women without COC. (C) 2007 Elsevier Inc. All rights reserved.

We followed a population-based cohort of 5696 women, 32–38 years of age, by registry linkage with cytology and pathology registries during a mean follow-up time of 4.1 years to assess the importance for CIN2+ development of type-specific HPV DNA positivity at baseline. HPV 16, 31 and 33 conveyed the highest risks and were responsible for 33.1, 18.3 and 7.7% of CIN2+ cases, respectively. Women infected with HPV 18, 35, 39, 45, 51, 52, 56, 58, 59 and 66 had significantly lower risks of CIN2+ than women infected with HPV 16. After adjustment for infection with other HPV types, HPV types 35, 45, 59 and 66 had no detectable association with CIN2+. In summary, the different HPV types found in cervical cancer show distinctly different CIN2+ risks, with high risks being restricted to HPV 16 and its close relatives HPV 31 and HPV 33.

For a long time the forest industry in Sweden has been waiting for nation-wide coverage by the GSM network. However, this has not been realized and therefore this thesis project was initiated, by H ...

OBJECTIVE:To measure the change of glucose in vaginal secretions during glucose tolerance testing in women with recurrent vulvovaginal candidiasis and in healthy control subjects. 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 beta value of 0.80, at the significance level of alpha=.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.

Background. Of the estimated one million Papanicolaou (pap) smears performed annually in Sweden, about 4% show any degree of abnormality. Approximately, 1% of these cases contain moderate or severe atypia (high-grade squamous intraepithelial lesions) and the rest contain low-grade atypia. Recommendations for the management of minor abnormalities vary in various parts of Sweden. Generally, a second Pap smear is obtained 4–6 months after the first one showing low-grade atypia. The aim of this study is to compare the sensitivity of human papilloma virus (HPV)-DNA testing for the detection of cervical intraepithelial neoplasia (CIN) 2–3 with that of a second Pap smear in women, who had low-grade atypia in their first Pap smear. Methods. Women with low-grade atypia in the Stockholm area, detected at a population-based cytology screening, were enrolled. A repeat Pap smear, HPV test, and colposcopically directed biopsies were obtained. For the detection of HPV, Hybrid Capture II (HC II) was used. Results. The HPV-DNA test was positive in 66% of the 177 participating women. The sensitivity of the second Pap smear and HPV-DNA test to detect CIN 2–3 was 61 (95% CI = 45–74) and 82% (95% CI = 67–91), respectively. The positive and negative predictive values of HPV testing were 27 (95% CI = 18–35) and 89% (95% CI = 80–97), respectively. Conclusions. In Sweden, a second Pap smear is often obtained for the follow-up of women with low-grade atypia. The results of our study show that compared to the second Pap smear, HPV testing with HC II is a more sensitive method for detecting high-grade lesions.

Objective: The purpose of this study was to determine whether there is an association between recurrent. vulvovaginal candida and chronic stress. Chronic stress affects the hypothalamus-pituitary-adrenal axis, which influences the immune function. Recurrent candida vulvovaginitis is increasing:Study design: Women with recurrent vulvovaginal candida (n = 35) and age-matched healthy control subjects (n = 35) collected saliva for the analysis of cortisol. Hormone analyses of blood samples and vulvovaginal examinations were performed. A questionnaire was completed.Results: Morning rise cortisol level was significantly blunted among patients compared with control subjects (P <.002). Mean levels of salivary cortisol were lower the first 45 minutes after awakening in women with recurrent vulvovaginal candida, compared with control subjects. More patients than control subjects reported a history of condyloma, bacterial vaginosis, and herpes genitalis. No differences were seen between patients and control subjects regarding sexual hormone binding globulin, dihydroepiandrosterone, testosterone or Hemoglobin A(1c).Conclusion: Morning rise salivary cortisol level is blunted in women with recurrent vulvovaginal candida, which indicates signs of chronic stress. The higher incidence of vulvovaginal infections in these women compared with control subjects may reflect impaired immunity, which may be due to chronic stress. (C) 2005 Mosby, Inc. All rights reserved.