Urethral instillations of clobetasol propionate and lidocaine: a promising treatment of urethral pain syndrome.

PURPOSE: To evaluate topical treatment with clobetasol propionate and lidocaine in women with urethral pain syndrome (UPS) in a retrospective pilot study. MATERIALS AND METHODS: Urethral instillations of two ml clobetasol propionate cream and two ml lidocaine gel in 30 Caucasian women age 15-74 years with UPS between 1999 and 2006 were evaluated retrospectively. Instillations were given ap- proximately once a week until the patient improved. Between one and 15 (median three) instillations were given. In substudy I a review was undertaken of the medical records to register the treatment effect at the end of the treatment (the last instillation) and any relapses six months thereafter. Substudy II was a follow-up at least five years after last instillation based on medical records and a written ques- tionnaire. RESULTS: Substudy I (n=30): By the end of the treatment 18 women had no symptoms and 12 were improved. Five patients had relapsed within six months. Substudy II (n=28): Twenty-eight women responded to the questionnaire. Four women remained with no symptoms, 18 remained improved, and six had the same symptoms as before treatment. Twenty women thought the treatment was very effective, five rather effective, and three women reported poor effect. Twenty-six women would ask for retreatment if a relapse oc- curred, two patients would not. No side effects, except transient pain, were reported. CONCLUSIONS: This retrospective study and long- term follow-up suggests that urethral instillation of clobetasol propionate and lidocaine is effective in treating women with UPS. Randomized control studies are warranted.

Trends over 30 years in the prevalence and severity of alveolar bone loss and the influence of smoking and socio-economic factors--based on epidemiological surveys in Sweden 1983-2013.

OBJECTIVE: Epidemiological studies of the prevalence of periodontitis over an extended time using the same methodology to investigate and classify periodontitis are sparse in the literature. Smoking and socio-economic factors have been proven to increase the risk for periodontal disease. The objective of this study was to investigate 30-year time trends, using the same methodology to classify the prevalence and severity in alveolar bone loss (ABL) and to investigate the influence of tobacco and socio-economic factors. METHODS: Four cross-sectional epidemiological studies in an adult population were performed in the county of Dalarna, Sweden, in 1983, 2003, 2008 and 2013. Random samples of 787-1133 individuals aged 35-85 who answered a questionnaire about tobacco use and socio-economic factors were radiographically and clinically examined. A number of teeth, ABL and calculus visible on radiographs were registered. The severity of ABL as detected on radiographs was classified into no bone loss, moderate or severe. RESULTS: The prevalence of moderate ABL decreased from 45% in 1983 to 16% in 2008, but increased to 33% in 2013 (P < 0.05). The prevalence of severe ABL remained the same from 1983 (7%) to 2013 (6%). Calculus visible on radiographs increased from 22% in 2008 to 32% in 2013 (P < 0.05). Socio-economic factors had limited impact on the severity of ABL. CONCLUSION: Moderate ABL and calculus visible on radiographs significantly increased between 2008 and 2013. Smoking was the strongest factor associated with ABL overall.

Correlation between LRIG1 and LRIG2 expressions and expression of 11 tumor markers, with special reference to tumor suppressors, in CIN and normal cervical epithelium.

OBJECTIVE: Novel biological markers LRIG1 and LRIG2 have been associated with favorable as well as poor prognosis, respectively, in different cancer types, including cervical cancer. The aim of this study was to investigate possible interactions between these proteins and other tumor markers, and as diagnostic adjuncts in CIN. METHODS: Cervical biopsies from 171 women, with normal epithelium, and low-grade and high-grade CIN were stained for LRIG1 and LRIG2, and 11 additional tumor markers. The tumor markers were chosen to be relevant in cervical neoplasms. Staining was evaluated semiquantitatively. RESULTS: Expression of LRIG1 and LRIG2 was found to correlate with increasing CIN grade, as well as with expression of tumor suppressor FHIT, independent of histological grade. In addition, tumor promoter LRIG2 expression correlated negatively with expression of tumor suppressor retinoblastoma protein and positively with IL-10. The latter correlation did not however remain after adjustment for CIN grade. p53 and p16 expressions correlated positively with LRIG1 expression in univariate analyses, but significance did not hold after adjustment for CIN grade. CONCLUSION: LRIG1 and LRIG2 expressions were seen in precancerous cervical epithelium and found to increase with increasing grade. There was an association between expression of these glycoproteins and FHIT tumor suppressor protein, independently of histological grade.

LRIG1 and squamous epithelial uterine cervical cancer: correlation to prognosis, other tumor markers, sex steroid hormones, and smoking.

The aim is to evaluate LRIG1 as a prognosis predictor and correlations to cofactors in squamous cell cervical cancer. LRIG1 expression was studied in 128 cervical carcinomas and was compared with expression of nine other tumor markers. Smoking history was registered and pretreatment serum estradiol and progesterone levels were evaluated in 79 women. At clinical stage IB, 58% of the tumors showed LRIG1 expression, but there was a decline by increasing stage (33% in stage IV). Ninety percent of women with stage IB cancer and LRIG1 positivity survived, as compared to 64% without expression (P = 0.02). LRIG1 expression did not predict prognosis in advanced stages, but in stage IIA there was a marked relative difference, with 75% survival in tumors expressing LRIG1, as compared to 43% in those without. No correlation was found between LRIG1 and the other nine tumor markers studied. A high serum progesterone and smoking correlated to absent LRIG1 expression. We conclude that LRIG1 appears to be a significant prognosis predictor in early-stage cervical cancer, independent of the other tumor markers that were studied. Diminished expression in advanced stages and the inverse correlation to serum progesterone and smoking indicates that LRIG1 is a tumor suppressor in cervix.

Correlations between serum progesterone and smoking, and the growth fraction of cervical squamous cell carcinoma.

BACKGROUND: Possible correlations between growth fraction of squamous cervical carcinomas and serum progesterone (se-P) concentrations, smoking habits and DNA ploidy were studied. MATERIALS AND METHODS: The DNA S-phase fraction (SPF), measured by flow cytometry was used as a marker of tumour growth in 103 cases of squamous cervical cancer stage IB-IV. DNA-ploidy (peridiploidy vs. aneuploidy), Se-P, se-Estradiol, smoking habits, parity, menopausal status, clinical stage and histopathological grading were compared to SPF < 14% vs. SPF > or = 14%. RESULTS: Aneuploidy, (odds ratio (OR) 10.0), se-P > or = 2.6 nmol/l (OR 7.5) and smoking (OR 3.0) were significantly associated with SPF > or = 14%, after adjustments for all factors included in the study. The association with se-P and smoking was attributed to an increased risk for the premenopausal women in the study. DISCUSSION: In this study an increased tumour growth was associated with increased leves of se-P, smoking and aneuploidy in women with invasive squamous cervical carcinoma. This study seems to experimentally confirm epidemiological studies, where smoking and long-term use of oral contraceptives have been linked to cervical neoplasms.

Pilot study to evaluate a new regimen to treat climacteric complaints with cyclic combined oestradiol valerate/medroxyprogesterone acetate.

Nineteen post-menopausal women suffering from climacteric complaints were treated with a cyclic regimen comprising 25 days on 2 mg oestradiol valerate and 5 mg medroxyprogesterone acetate daily, followed by a 5-day treatment-free interval. The mean duration of treatment was 20.2 mth. Control of bleeding was good; 9 women had slight monthly bleeding, 8 no bleeding at all, and 2 had only irregular spotting during the follow-up period. An endometrial biopsy was taken in 9 women in whom the mean duration of treatment was 30 mth. All endometrial biopsies showed an atrophic endometrium. A larger, randomized comparative study is now planned.

Comparison of a triphasic oestradiol/norethisterone acetate preparation with and without an oestriol component in the treatment of climacteric complaints.

This study was undertaken to evaluate the effects of oestriol in combination with oestradiol in the treatment of women with climacteric complaints. Forty-three post-menopausal women were randomly allocated to two groups on a double-blind basis. Over a 28-day cycle 23 of the women were treated sequentially for 12 days with 1 tablet containing 17 beta-oestradiol 2 mg plus oestriol 1 mg, then for 10 days with 1 tablet containing the same oestrogens plus norethisterone acetate 1 mg, thereafter for 6 days with 1 tablet containing 17 beta-oestradiol 1 mg plus oestriol 0.5 mg. The other 20 women received the same treatment but without the oestriol. No clinical, laboratory or histological differences were seen between the two groups. Both treatments were found to be equally effective in alleviating climacteric symptoms, with few side effects. It may be stated in conclusion that, on the basis of routine clinical and laboratory parameters no differences were found between the two preparations.

Clinical and endometrial effects of oestradiol and progesterone in post-menopausal women.

This study reports the clinical effects in a group of post-menopausal women after 4 months of treatment with 2 mg micronized 17 beta-oestradiol (E2) in combination with different doses of micronized progesterone (50, 100 or 200 mg) for 25 days each month. The 30 participants were divided into three groups. All of the subjects tolerated the preparation well and obtained relief from their climacteric complaints. None dropped out because of side effects and no changes were observed in blood pressure, weight or Papanicolaou cytology. Breakthrough bleeding was noted in the first cycle, mainly in the group receiving the lowest dose of progesterone. Endometrial biopsies performed before and after 4 months of treatment showed an atrophic endometrium in most of the women who received 100 mg progesterone and in all of the women on 200 mg progesterone. The results showed that this new combination of 2 mg E2 and micronized progesterone in different doses was both effective and well accepted.

Long-term use of oral contraceptives and cervical neoplasia: an association confounded by other risk factors?

One-hundred-and-forty women with cervical intraepithelial neoplasia (CIN) found during pregnancy were compared to 280 pregnant age-matched controls. Information was obtained on obstetrical and gynecological history, sexual behaviour, contraceptive use and smoking of the female and of the male partner. Oral contraceptive use for 60 months or more was significantly associated with CIN. This significance vanished when the effect of confounding factors was controlled for in a log-linear analysis. According to these results, long-term oral contraceptive use does not seem to be a causal factor of CIN, but these women constitute a high risk group due to sexual history and smoking habits and should thus be referred for a regular cytological screening.

Contraceptive use in women with bacterial vaginosis.

The aim of the study was to investigate if bacterial vaginosis (BV) is associated with use of specific contraceptives. Women at family planning and youth clinics (n = 956), among whom 131 had BV, were subjects for structured in-depth interviews including current and previous contraceptive use. Variables measuring sexual risk-taking were ascertained. Current users of contraceptives were compared with non-users. Both oral contraceptive (OC) and condom use showed a significant protective effect against BV, adjusted for possible confounders (odds ratios were 0.4 and 0.3, respectively). Intrauterine device use (IUD) showed no association with BV. Women with BV had less often used any contraceptives, including condom, at their sexual debut than the women in the comparison group. In this study, OC and condom use seemed to exert a protective effect against BV, whereas no effect for IUD use was found.

PIP: To determine whether bacterial vaginosis (BV) is associated with use of specific contraceptive methods, 956 women from family planning and youth clinics at 3 Swedish hospitals were enrolled in a cohort study. 131 women had at least 3 of the 4 clinical signs of BV: a homogenous gray vaginal discharge, a vaginal pH of 4.7, a positive amine test, and the presence of "clue" cells. Age at first intercourse was 16 years among those with and without BV; however, 8.4% of women with BV, compared with only 1.7% of controls, had had more than 1 sex partner in the last 6 months. Other factors associated with BV were more than 10 lifetime sex partners, non-use of contraception at first intercourse, a history of sexual abuse, an induced abortion, smoking, and alcohol consumption. After adjustment for sexual risk-taking, there was a significant negative association between BV and oral contraceptive (OC) use (odds ratio [OR], 0.4; 95% confidence interval [CI], 0.2-0.8). There was also a significant negative association with condom use (OR, 0.3; 95% CI, 0.1-0.9). There was no association between BV and IUD use, before or after adjustment for confounding factors. Insufficient numbers of diaphragm or spermicide users were available for analysis. The finding of an apparently protective effect against BV of OCs and condoms lacks a biological explanation at present, although it is speculated that OC use increases the glycogen content of vaginal epithelial cells, in turn inhibiting the in vitro growth of certain bacteria.

Long-interval treatment regimen with a desogestrel-containing oral contraceptive.

A randomized multicenter study was performed in order to investigate the acceptance of a low-dose OC (30 micrograms of ethinyloestradiol and 150 micrograms of desogestrel), using a 9 weeks on and 1 week off schedule (prolonged regimen, n = 198), compared to a traditional 3 weeks on, 1 week off schedule (standard regimen, n = 96). Haemoglobin and blood pressure remained the same in both groups during the study. No significant differences were found in body weight changes between the two groups. There was significantly more breakthrough bleeding and spotting in the group with prolonged regimen than in the group with standard regimen, but both breakthrough bleeding and spotting decreased during the trial. Irregular bleeding was significantly less in women who were already using OC, compared to "new starters." No serious side effects occurred. Significantly more women stopped the trial because of bleeding problems in the group with prolonged regimen, while there were significantly more women who stopped the trial because of headache in the group with standard regimen. After completing 12 months, or after premature withdrawal from the study, each women completed a questionnaire. Sixty-three per cent of the women preferred the studied alternative and twenty-six per cent preferred the traditional OC.

Hemostasis profile and lipid metabolism with long-interval use of a desogestrel-containing oral contraceptive.

Thirty healthy women, aged 18 to 37, were randomly allocated to treatment with a desogestrel-containing oral contraceptive, with 20 women using a nine-week on, one-week off regimen, and 10 women using the traditional regimen. At 0, 3 and 12 months, blood samples were drawn for liver proteins, lipoproteins and hemostatic variables. No significant changes were observed between the two regimens. Sex hormone binding globulin (SHBG) and corticosteroid binding globulin (CBG, transcortin) were increased two- to four-fold, as a measure of estrogenicity. Minimal changes occurred within the lipoprotein cholesterol fractions, whereas there were some increases within the lipoprotein triglyceride fractions. Among the hemostatic variables, there were significant increases of fibrinogen, factor VII and thrombin/antithrombin III (TAT) complex. The coagulation inhibitors, antithrombin III, protein C and protein S, were essentially unchanged. A decrease of both tissue plasminogen activator antigen (t-PA) and tissue plasminogen activator inhibitor activity (PAI activity) of the fibrinolytic system was observed. A nine-week regimen does not seem to alter lipid metabolism and coagulation more than a three-week regimen.

PIP: Clinicians followed 30 women, 18-37 years old, attending the family planning clinic of Falu Hospital in Sweden to compare the effect of a long interval of an oral contraceptive (OC) (30 mcg ethinyl estradiol + 150 mcg desogestrel) on the hemostasis system, lipid metabolism, and hormone binding proteins with that of a traditional 3-week regimen. They randomly allocated 20 women to the long-interval group (group I) and 10 to the 3-week group (group II). The long-interval consisted of 9 weeks taking the OC and 1 week not taking the OC. Between baseline and 12 months, sex hormone binding globulin (SHBG) levels increased 409% in group I (p .001) and 341% in group II (p .01). Corticosteroid binding globulin (CBG) levels increased 294% (p .001) for group I and 173% for group II. SHBG and CBG levels (markers of estrogenicity) were not significantly different between the 2 groups, however. Limited, insignificant changes took place with lipoprotein cholesterol fractions. VLDL-triglycerides and LDL-triglycerides increased significantly in group I (0.31-0.57 mmol/l) and group II (0.21-0.27 mmol/l) (p .05). Fibrinogen, factor VII, and thrombin/antithrombin III complex increased significantly in group I at 3 and 12 months. They had also increased in group II but not significantly. The coagulation inhibitors (i.e., antithrombin III, protein C, and protein S) remained virtually the same. Levels of tissue plasminogen activator antigen and tissue plasminogen activator inhibitor activity, both of the fibrinolytic system, fell (significant decrease only in group I). These findings show that the desogestrel-containing low-dose OC has limited effects on lipid metabolism, particularly the cholesterol subfractions, regardless of the regimen. It does increase minimally coagulation parameters, but the fibrinolytic system offsets this increase. In conclusion, the long-interval regimen is as safe as the 3-week regimen.

Bacterial vaginosis and smoking.

This study aimed to investigate if there is an association between bacterial vaginosis (BV) and smoking. This cohort study included 956 randomly chosen, apparently healthy women at 2 family planning and one youth clinic. Of the 956 women, 131 women fulfilled the criteria for BV and the remaining 825 served as a control group. BV, BV-associated bacteria and gynaecological infections were diagnosed. Structured personal interviews concerning, smoking, alcohol and drug habits, sexual behaviour and reproductive history were made. Before and after adjustment for possible confounding factors, smoking, but not alcohol and drug use, was significantly associated with BV. Of the women with BV 52% were smokers versus 32% in the control group. Age-adjusted odds ratio (OR) for smokers was 2.3 before, and 3.0 (95% confidence interval [CI] 1.3-6.9) after adjustment for sexual risk behaviour, reproductive history, and alcohol use. There was also a significant dose-response relationship between BV and smoking habits. The data suggest that there might be a causal association between BV and smoking.

Self-treatment of female external genital warts with 0.5% podophyllotoxin cream (Condyline) vs weekly applications of 20% podophyllin solution.

Sixty women with genital warts were randomly allocated to treatment with either weekly application of 20% podophyllin solution or self-treatment with 0.5% podophyllotoxin cream twice daily for three days in weekly intervals. After a maximum of 4 treatment cycles a final assessment was carried out after 3 months. Primary clearance after termination of treatment was 82% for podophyllotoxin and 59% for podophyllin solution. After excluding relapses at the 3-month follow-up, final clearance for podophyllotoxin (71%) was significantly better (P < 0.05) than that for podophyllin solution (48%). The total frequency of warts eradicated was 94% with podophyllotoxin and 74% with podophyllin solution (P < 0.001). Local adverse effects were generally mild or moderate. Podophyllotoxin cream provides a mode of easy application for women with external genital warts and had in this study a significantly better effect than podophyllin solution.

Culture and wet smear microscopy in the diagnosis of low-symptomatic vulvovaginal candidosis.

OBJECTIVES: To compare the clinical usefulness of culture and wet smear microscopy in low-symptomatic vulvovaginal candidosis (VVC) diagnosis. STUDY DESIGN: Women attending for contraceptive advice were screened for vaginal yeast fungi by culture and wet smear microscopy. A positive culture was found in 130 (13.2%) of the 983 women studied, while a positive wet smear was found in 133 (13.9%). In 40 (30%) of these women both the culture and wet smear was positive. RESULTS: The methods were equally sensitive in predicting symptoms of VVC, such as pruritus, smarting and burning pain, as well as for dyspareunia (35% vs. 36%), but wet smear microscopy was more sensitive in predicting signs of VVC, such as erythema and abnormal discharge (52% vs. 34%). The highest sensitivity was reached when both methods were positive (60% for symptoms, 75% for signs). There was no quantitative correlation between number of Candida colonies on culture on the one hand and symptoms, signs or a positive wet smear on the other hand. Using four parameters as a diagnostic battery for VVC, the two methods complemented each other. The correlation between symptoms and/or signs for wet smear was high than for culture. CONCLUSION: Wet smear microscopy of vaginal secretion, along with signs found at examination, should be the first-line test in the diagnosis of VVC. Culture must, however, be used when there is a clinical suspicion of VVC and a negative wet smear, or when speciation or antibiotic susceptibility tests of isolates are required.

Premenstrual tension: a placebo-controlled efficacy study with spironolactone and medroxyprogesterone acetate.

Forty-three healthy women with a characteristic history of premenstrual tension participated in a placebo controlled, crossover study. The effects of spironolactone (Aldactone) and medroxyprogesterone acetate (Gestapuran) on ten symptoms of premenstrual tension were evaluated. Placebo tablets as well as spironolactone and medroxyprogesterone acetate significantly improved a mood index score (which is a generally accepted method to measure premenstrual symptoms). Spironolactone and medroxyprogesterone acetate were however both significantly (P less than 0.05) better than placebo in relieving the symptoms.

Symptoms and signs in single and mixed genital infections.

OBJECTIVE: To compare symptoms and signs in women with single and mixed genital infections. METHODS: The study population comprised 996 apparently healthy women. Gynecological symptoms and signs were looked for and diagnostics for the most prevalent gynecological infections were made. RESULTS: When co-infections were excluded, chlamydial infections, bacterial vaginosis and cervical human papillomavirus infections were associated with a fishy malodor; for the two former conditions an easily bleeding ectopy was also found. Vaginal candidosis showed characteristic symptoms and signs. Genital warts were associated with dysuria, general and lower abdominal pain. Out of 494 women with a genital infection, 112 (22.7%) had a mixed infection, which in some cases influenced symptoms and signs. CONCLUSION: Many women who consider themselves gynecologically healthy, may nevertheless harbor one or more infectious agents. The need to exclude multiple infections is obvious. Positive predictive values were for specific symptoms and signs were generally low.

Immunohistochemical LRIG3 expression in cervical intraepithelial neoplasia and invasive squamous cell cervical cancer: association with expression of tumor markers, hormones, high-risk HPV-infection, smoking and patient outcome.

The novel biomarker LRIG3 is a member of the LRIG family (LRIG1-3). While LRIG1 has been associated with favorable prognosis and LRIG2 with poor prognosis in invasive cervical cancer, little is known about the role of LRIG3. The aim of this study was to investigate the expression of LRIG3 in invasive cancer and cervical intraepithelial neoplasia (CIN) for possible correlation with other tumor markers, to hormones and smoking, as a diagnostic adjunct in CIN, and prognostic value in invasive cancer. Cervical biopsies from 129 patients with invasive squamous cell carcinoma and 170 biopsies showing low grade and high grade CIN, or normal epithelium were stained for LRIG3 and 17 additional tumor markers. Among other variables the following were included: smoking habits, hormonal contraceptive use, serum progesterone, serum estradiol, high-risk HPV-infection, menopausal status and ten-year survival. In CIN, high expression of the tumor suppressors retinoblastoma protein, p53, and p16, and E-cadherin (cell-cell interaction), or low expression of CK10, correlated to LRIG3 expression. In addition, progestogenic contraceptive use correlated to high expression of LRIG3. In invasive cancer there was a correlation between expression of the major tumor promoter c-myc and high LRIG3 expression. High LRIG3 expression correlated significantly to presence of high-risk HPV infection in patients with normal epithelium and CIN. There was no correlation between LRIG3 expression and 10-year survival in patients with invasive cell cervical cancer. LRIG3 expression is associated with a number of molecular events in CIN. Expression also correlates to hormonal contraceptive use. The results on expression of other tumor markers suggest that LRIG3 is influenced by or influences a pattern of tumor markers in cancer and precancerous cells. Further studies are needed to elucidate if LRIG3 expression might be clinically useful.

Disease Extent ≥4 cm Is a Prognostic Marker of Local Recurrence in T1-2 Breast Cancer.

Despite improvements of the therapy for breast cancer, a proportion of the patients still get local recurrence. The status of the surgical margins is the most often used parameter for decision regarding additional treatment. However, a negative margin is not a guarantee that there is not residual cancer left in the breast; additional parameters are needed to better predict the risk of local recurrence. The disease extent was evaluated in the surgical specimen from 313 women after breast-conserving therapy using large-section histology and was correlated to the incidence of local recurrence. A disease extent ≥4 cm was shown to be an independent marker for local recurrence; the cumulative 10-year local relapse rate for the group with a disease extent ≥4 cm was 20.5%, and for the rest 6.7%. We conclude that disease extent ≥4 cm seems to be an important factor when evaluating the risk for local recurrence.