Newly developed vaginal atrophy symptoms II and vaginal pH: a better correlation in vaginal atrophy?

OBJECTIVES: The primary objective of this study was to evaluate the correlation among symptoms, signs, and the number of lactobacilli in postmenopausal vaginal atrophy. The secondary objective was to develop a new parameter to improve the correlation. STUDY DESIGN: A cross-sectional descriptive study. METHODS: Naturally postmenopausal women aged 45-70 years with at least one clinical symptom of vaginal atrophy of moderate to severe intensity were included in this study. All of the objective parameters (vaginal atrophy score, vaginal pH, the number of lactobacilli, vaginal maturation index, and vaginal maturation value) were evaluated and correlated with vaginal atrophy symptoms. A new parameter of vaginal atrophy, vaginal atrophy symptoms II, was developed and consists of the two most bothersome symptoms (vaginal dryness and dyspareunia). Vaginal atrophy symptoms II was analyzed for correlation with the objective parameters. RESULTS: A total of 132 naturally postmenopausal women were recruited for analysis. Vaginal pH was the only objective parameter found to have a weak correlation with vaginal atrophy symptoms (r = 0.273, p = 0.002). The newly developed vaginal atrophy symptoms II parameter showed moderate correlation with vaginal pH (r = 0.356, p < 0.001) and a weak correlation with the vaginal atrophy score (r = 0.230, p < 0.001). History of sexual intercourse within 3 months was associated with a better correlation between vaginal atrophy symptoms and the objective parameters. CONCLUSION: Vaginal pH was significantly correlated with vaginal atrophy symptoms. The newly developed vaginal atrophy symptoms II was associated with a better correlation. The vaginal atrophy symptoms II and vaginal pH may be better tools for clinical evaluation and future study of the vaginal ecosystem.

Ultra-low-dose estriol and lactobacilli in the local treatment of postmenopausal vaginal atrophy.

OBJECTIVE: The aim of this study was to demonstrate the efficacy of an ultra-low-dose vaginal estriol 0.03 mg in combination with viable Lactobacillus acidophilus KS400 (Gynoflor(®) vaginal tablets) in the short-term therapy and to investigate the long-term maintenance dose in the treatment of vaginal atrophy. METHODS: This was a double-blind, randomized, placebo-controlled study (Controlled phase--initial therapy) followed by an open-label follow-up (Open phase--test medication initial and maintenance therapy). Included were postmenopausal women with vaginal atrophy symptoms and Vaginal Maturation Index (VMI) of ≤ 40%. The method of treatment was initial therapy with test medication (or placebo in first phase), one vaginal tablet daily for 12 days, followed by maintenance therapy, one tablet on two consecutive days weekly for 12 weeks. RESULTS: A total of 87 women completed the study. The Controlled phase results for a change in VMI demonstrated superiority of the 0.03 mg estriol-lactobacilli combination to placebo (p < 0.001). In the test group, the positive change in VMI was 35.2%, compared to 9.9% in the placebo group. In the Open phase after the initial therapy, the VMI was increased to 55.4% and, during maintenance therapy, it stayed at a comparable level (52.8-49.4%). The maturation of epithelium was followed by improvement of clinical symptoms and normalization of the vaginal ecosystem. CONCLUSIONS: The ultra-low-dose, vaginal 0.03 mg estriol-lactobacilli combination (Gynoflor(®)) was superior to placebo with respect to changes in VMI after the 12-day initial therapy, and the maintenance therapy of two tablets weekly was sufficient to prevent the relapse of vaginal atrophy.

LINE-1 hypomethylation level as a potential prognostic factor for epithelial ovarian cancer.

A genome-wide hypomethylation is a common and crucial event in cancer. This study was to evaluate common epithelial ovarian cancer (EOC) if long interspersed element-1 (LINE-1) repetitive sequences methylation levels are progressively decreased during multistage carcinogenesis and there are the correlation between LINE-1 methylation levels and clinicopathologic characteristics. A total of 59 pairs of microdissected EOC tissues obtained from patients with EOC were examined for the methylation levels of LINE-1 repetitive sequences by a COBRALINE-1 (combined bisulfite restriction analysis of LINE-1) PCR protocol. The methylation levels were correlated with clinicopathologic parameters to determine the potential role of global hypomethylation as a prognostic marker for EOC. The LINE-1 methylation levels of 59 EOCs, 34.87 +/- 7.39%, were lower than in representative normal ovarian tissues (46.89 +/- 8.31%; 95% CI: 9.42-14.62; P < 0.001, paired-two-tailed t test). A decrease in the LINE-1 level of methylation was correlated with histological subtypes, higher FIGO and advanced tumor grade. Patients with greater hypomethylation (i.e., a methylation level

Angiogenesis in cervical intraepithelial neoplasia and early-staged uterine cervical squamous cell carcinoma: clinical significance.

The objective of this study is to evaluate angiogenesis in cervical intraepithelial neoplasia (CIN), microinvasive squamous cell carcinoma (MIC), and early-staged squamous cell carcinoma (SCC), stage IB-IIA of the cervix. Microvessel density (MVD) was evaluated and correlated with other pathologic prognostic factors and disease outcomes. Four hundred seventy-four cervical specimens were studied. Among these, 100 were designated normal cervix, 30 CIN1, 32 CIN2, 178 CIN3, 74 MIC, and 60 early-staged SCC. MVD per high-power field (x400) of early-staged SCC, MIC, and CIN3 were significantly higher in comparison to CIN2, CIN1, and control subjects (P<0.05). There was no statistically significant difference in MVD between control group, CIN1, and CIN2. In early-staged SCC, no correlation between MVD and pelvic lymph node status, parametrial involvement, depth of stromal invasion, and lymphovascular space invasion was found. Patients with bad outcomes (recurrence or death) showed no statistically different MVD from the ones who had unremarkable clinical courses.

Fibroblast growth factor receptor 3 S249C mutation in virus associated squamous cell carcinomas.

An S249C mutation in fibroblast growth factor receptor 3 (FGFR3) gene was recently identified in patients with cervical carcinomas (CC). However, its importance in cervical tumorigenesis is still inconclusive. Apart from CC, nasopharyngeal carcinoma (NPC) is the other major virus associated squamous cell carcinoma. We sought to clarify the frequency of the FGFR3 S249C mutation in 75 primary CC in the Thai population and to determine its prevalence in 69 primary NPC by PCR and restriction enzyme digestion. None of the patients but one NPC showed the enzyme digestion pattern consistent with the mutation. This is the first report demonstrating the role of FGFR3 in the development of human NPC. This study confirms the low frequency of the FGFR3 S249C mutation in CC. Nevertheless, the discovery of the mutation, not only in CC as reported by previous studies, but in NPC based on this report, suggests that FGFR3 may play a significant role in human CC and NPC development.

Pipelle versus fractional curettage for the endometrial sampling in postmenopausal women.

The experimental and cross over design study was performed to compare the pain, ability to sample the endometrial issue, and pathological results from pipelle and fractional curettage in post menopausal patients. Thirty naturally menopausal patients who visited King Chulalongkorn Memorial Hospital with abnormal bleeding per vagina from June 1 to December 31, 1997, were enrolled in the study. In group A,endometrial tissue sampling was first conducted by Pipelle and followed by fractional curettage. In group B, the fractional curettage was performed before Pipelle. The results showed that the pain derived by the visual analogue scale of Pipelle and fractional curettage were 3.34 +/- 1.44 (mean +/- SD) and 6.58 +/- 1.75 respectively (p<0.01). The sensitivity and specificity of Pipelle in endometrial tissue samplings compared with fractional curettage were 87.5 and 100 per cent, respectively. One from 3 cases of adeneocarcinoma of the endometrium could not be detected by Pipelle. In conclusion, Pipelle significantly produced less pain than fractional curettage. Even though Pipelle is a simple and easy method for endometrium sampling, the use of Pipelle to replace fractional curettage in the management of postmenopausal bleeding should be done with caution. False negative could occur in the focal disease of malignancy of the endometrium.

The role of maternal serum C-reactive protein and white blood cell count in the prediction of chorioamnionitis in women with premature rupture of membranes.

This study was performed to evaluate the diagnostic performance of maternal serum C-reactive protein, maternal white blood cell (WBC), and neutrophil counts in the detection of histologic chorioamnionitis. One hundred and twenty six pregnant women after at least 28 weeks of gestation with premature rupture of membranes (PROM) were studied. Blood samples for C-reactive protein, WBC and neutrophil counts were taken at delivery. Placental histology was evaluated for histologic chorioamnionitis. Maternal and neonatal complications were observed. Among women with and without histologic chorioamnionitis, the maternal WBC and neutrophil counts were different (P<0.05) but the maternal serum C-reactive protein was not. Cutoff values for C-reactive protein, WBC, and neutrophil counts were 0.5 mg/dL, 15,000 cell/mm3, and 80 per cent, respectively. Sensitivity and specificity were 56 per cent and 58 per cent for C-reactive protein, 60 per cent and 63 per cent for WBC count, and 62 per cent and 54 per cent for neutrophil count, respectively. In conclusion, the maternal serum C-reactive protein, WBC, and neutrophil counts have poor diagnostic performance for histologic chorioamnionitis.

Uterine perforation with Lippes loop intrauterine device-associated actinomycosis: a case report and review of the literature.

A case of a 67-year-old postmenopausal woman, gravida 2, para 2, with an uterine perforation from actinomycotic infection with Lippes loop IUD is reported. She had the Lippes loop IUD inserted for 35 years, and had never had any pelvic examination nor Papanicolaou smear. She presented with acute abdominal pain. The clinical picture mimicked peptic ulcer perforation. The woman underwent laparotomy and exudative fluid was discovered in the abdominal cavity with the tip of the Lippes loop IUD at one of the two small holes of the uterine fundus. Total abdominal hysterectomy with bilateral salpingo-oophorectomy was performed. The postoperative microscopic pathological report demonstrated characteristics of actinomycosis. She was treated with parenteral high-dose penicillin for 4 weeks followed by oral penicillin for 6 months. The woman had an uneventful recovery. To our knowledge, this is the first case report of uterine perforation due to Lippes loop IUD-associated actinomycotic infection.

Effects of clomiphene citrate on the endometrium of regularly cycling women.

OBJECTIVE: To study the effects of clomiphene citrate (CC) on the endometrium of regularly cycling women. DESIGN: Prospective, controlled study. SETTING: Department of Obstetrics and Gynaecology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. PATIENT(S): Thirty healthy, regularly cycling, female volunteers. INTERVENTION(S): All volunteers were studied for two consecutive cycles, one control cycle and one CC-treated cycle. Clomiphene citrate (100 mg/d) was given on days 3-7 of the CC-treated cycles. Ultrasonography was performed daily to assess ovulation. Ultrasonography and endometrial biopsy were performed, and blood samples were obtained for determination of E2 and progesterone levels 7 days after ovulation in both the control and CC-treated cycles. MAIN OUTCOME MEASURE(S): Histologic dating, morphometric analysis, and ultrasonographic appearance and thickness of the endometrium. RESULT(S): Histologic dating and ultrasonographic appearance and thickness of the endometrium were similar in the control and CC-treated cycles, but morphometric parameters were different. The number of glands per square millimeter and the mean diameter of the glands were lower in the CC-treated cycles than in the control cycles, but the number of vacuolated cells per 1,000 glandular cells was higher. CONCLUSION(S): Clomiphene citrate has effects on the endometrium of regularly cycling women, as demonstrated by a reduction in glandular density and an increase in the number of vacuolated cells.

The effect of transdermal oestradiol on bleeding pattern, hormonal profiles and sex steroid receptor distribution in the endometrium of Norplant users.

The most common side-effect and reason for discontinuation with Norplant use is bleeding disturbance. The aim of this study was to investigate whether the 6 week application of a patch which released 100 micrograms/day oestradiol would reduce the number of abnormal bleeding days or eliminate the problem. Another objective was to find out the correlation between the bleeding pattern and endometrial concentrations of oestrogen receptor (ER) and progesterone receptor (PR). Of 98 Norplant users, 34 patients had normal bleeding patterns and 64 patients had abnormal bleeding patterns. An oestradiol patch or a placebo patch were randomly used to treat 33 and 31 women with abnormal bleeding respectively. There was a clinical improvement in the oestradiol group compared with the placebo group, although this was not statistically significant. There were no correlations between PR and ER concentration and the serum oestradiol, progesterone, levonorgestrel and sex hormone-binding globulin concentrations. Significantly increased mean immunostaining scores of stromal PR were observed in those Norplant users whose endometrium had an atrophic histological appearance. The serum oestradiol concentration did not show a significant change after treatment with the oestradiol patch compared with the placebo patch.

PIP: The potential of an estradiol patch (100 mcg/day for 6 weeks) to reduce the menstrual disturbances associated with progestogen-only contraception was investigated in 98 Norplant users. Of the 64 subjects reporting abnormal bleeding, 33 were given an estradiol patch and 31 received a placebo patch; the 34 Norplant users with normal bleeding patterns served as controls. Clinical improvement was recorded in 23 estradiol patch and 13 placebo patch subjects, a nonsignificant difference. Ovarian activity, demonstrated by fluctuating high levels of estrogen, occurred in most Norplant users, but without ovulation. Serum levonorgestrel concentrations ranged from 1000 to 1500 pmol/l, with no significant differences according to group. Sex hormone-binding globulin (SHBG) levels were low (range, 20-50 nmol/l), again with no significant group differences. Both levonorgestrel and SHBG concentrations were steadier in women with normal bleeding patterns. Histology revealed that endometrial specimens from Norplant users were more atrophic than proliferative. Significantly increased mean immunostaining scores of stromal progesterone receptor were noted in Norplant users whose endometrium appeared atrophic. Also observed were low estrogen receptor concentrations in both glandular and stromal compartments. Overall, these findings suggest that progestogen-related bleeding abnormalities are related to the bioavailability of estrogen and progesterone receptors in the endometrium rather than histological changes.