Efficacy, safety and acceptability of a benzalkonium chloride spermicide cream in women aged 40 years and over needing contraception: A prospective multicentre study.

OBJECTIVE: This multicenter prospective study (BZK40+) aims to determine the efficacy and tolerance of a benzalkonium chloride-containing spermicide as contraceptive among women aged 40 and over. PROCEDURE: Fertile women enrolled in this open single-arm study were instructed to systematically use the benzalkonium chloride spermicide before each intercourse. At the end of a 6-month mandatory period, participants were given the option of continuing the study for a further 6 months. The primary endpoint for contraceptive efficacy was the Pearl Index (PI) up to 12 months of typical use. MAIN FINDINGS: A total of 151 women (mean age: 45.9 years) were enrolled, 144 (95.4%) completed the initial 6-month period and 63 (41.7%) completed the optional 6-month period. The median number of intercourses ranged from 3 to 5 per month. The spermicide was applied before 96.3% of the 5,895 sexual intercourses. The PI up to 12 months of typical use was 0 pregnancies (95% confidence interval: 0-2.88). The cumulative treatment exposure was 1249.7 women-months. CONCLUSION: This first study in women aged 40 years and over shows that benzalkonium chloride spermicide (Pharmatex®) is effective, well tolerated and well accepted in this population. Although very interesting, these results with a PI equal to zero are surprising and not in accordance with the low efficacy of spermicides in the overall population according to the WHO. So, our results should be interpreted with caution and confirmed by future research. Clinical trial registration number (EudraCT): 2016-004,188-38.

Estimating the Burden of Illness Related to Genital Warts in Russia: A Cross-Sectional Study.

BACKGROUND: Human papillomavirus (HPV) infections are the etiologic agents of genital warts (GW). HPV is one of the most frequent sexually transmitted viral infections, and nearly 65% of individuals with partners who have GW also develop GW. In Russia, as in many other countries, overall GW prevalence data are scarce. Given the lack of Russian data, our study estimated GW prevalence in physician practices and GW-related health care resource use in Russia among male and female patients aged 18-60 years. METHODS: Russian physicians recorded daily patient logs for a two-week period and conducted a 30-minute survey to estimate GW prevalence and related resource use between January and June 2012. Age, gender, and GW diagnosis status was recorded. Prevalence was obtained for each physician and calculated into a single estimate across all physician types. Overall prevalence estimate and 95% confidence interval were weighted by the estimated number of physicians in each specialty and the proportion of total patients visiting each specialist type. Health care resource use was reported and compared among different physician specialties. RESULTS: The overall GW prevalence estimate was 9162 cases per 100 000 for male and female patients aged 18-60 years, with 9917 for obstetrician/gynecologists (OB/GYN), 8298 for urologists (URO), and 7833 for dermatologists (DERM). For males, GW prevalence was 8769 cases per 100 000, with the highest prevalence in the 30-34 age group. In females, GW prevalence was 9304 cases per 100 000, with the highest prevalence in the 18-24 age group. Among overall existing GW cases, 63.1% were recurrent and 34.2% were resistant. For all patients in our study, GW prevalence was higher in females. Male patients had the highest prevalence for those aged 30-34 years, and female patients for those aged 18-24 years. These results are consistent with data reported in other countries. Study limitations include estimates and results representative of the urban population of Russia. Despite its limitations, this study provides a GW prevalence estimate in Russia not previously available. CONCLUSIONS: GW is a significant public health concern in Russia, and the GW prevalence was higher in female patients compared to male patients.

Efficacy, safety, and immunogenicity of the human papillomavirus 16/18 AS04-adjuvanted vaccine in women older than 25 years: 7-year follow-up of the phase 3, double-blind, randomised controlled VIVIANE study.

BACKGROUND: Although the risk of human papillomavirus (HPV) infection is greatest in young women, women older than 25 years remain at risk. We present data from the VIVIANE study of the HPV 16/18 AS04-adjuvanted vaccine in adult women after 7 years of follow-up. METHODS: In this phase 3, double-blind, randomised controlled trial, healthy women older than 25 years were enrolled (age stratified: 26-35 years, 36-45 years, and ≥46 years). Up to 15% in each age stratum had a history of HPV infection or disease. Women were randomly assigned (1:1) to receive HPV 16/18 vaccine or aluminium hydroxide control, with an internet-based system. The primary endpoint was vaccine efficacy against 6-month persistent infection or cervical intraepithelial neoplasia grade 1 or greater (CIN1+) associated with HPV 16/18. We did analyses in the according-to-protocol cohort for efficacy and total vaccinated cohort. Data for the combined primary endpoint in the according-to-protocol cohort for efficacy were considered significant when the lower limit of the 96·2% CI around the point estimate was greater than 30%. For all other endpoints and cohorts, data were considered significant when the lower limit of the 96·2% CI was greater than 0%. This study is registered with ClinicalTrials.gov, number NCT00294047. FINDINGS: The first participant was enrolled on Feb 16, 2006, and the last study visit took place on Jan 29, 2014. 4407 women were in the according-to-protocol cohort for efficacy (n=2209 vaccine, n=2198 control) and 5747 women in the total vaccinated cohort (n=2877 vaccine, n=2870 control). At month 84, in women seronegative for the corresponding HPV type in the according-to-protocol cohort for efficacy, vaccine efficacy against 6-month persistent infection or CIN1+ associated with HPV 16/18 was significant in all age groups combined (90·5%, 96·2% CI 78·6-96·5). Vaccine efficacy against HPV 16/18-related cytological abnormalities (atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesion) and CIN1+ was also significant. We also noted significant cross-protective efficacy against 6-month persistent infection with HPV 31 (65·8%, 96·2% CI 24·9-85·8) and HPV 45 (70·7%, 96·2% CI 34·2-88·4). In the total vaccinated cohort, vaccine efficacy against CIN1+ irrespective of HPV was significant (22·9%, 96·2% CI 4·8-37·7). Serious adverse events related to vaccination occurred in five (0·2%) of 2877 women in the vaccine group and eight (0·3%) of 2870 women in the control group. INTERPRETATION: In women older than 25 years, the HPV 16/18 vaccine continues to protect against infections, cytological abnormalities, and lesions associated with HPV 16/18 and CIN1+ irrespective of HPV type, and infection with non-vaccine types HPV 31 and HPV 45 over 7 years of follow-up. FUNDING: GlaxoSmithKline Biologicals SA.

Progression of HPV infection to detectable cervical lesions or clearance in adult women: Analysis of the control arm of the VIVIANE study.

The control arm of the phase III VIVIANE (Human PapillomaVIrus: Vaccine Immunogenicity ANd Efficacy; NCT00294047) study in women >25 years was studied to assess risk of progression from cervical HPV infection to detectable cervical intraepithelial neoplasia (CIN). The risk of detecting CIN associated with the same HPV type as the reference infection was analysed using Kaplan-Meier and multivariable Cox models. Infections were categorised depending upon persistence as 6-month persistent infection (6MPI) or infection of any duration. The 4-year interim analysis included 2,838 women, of whom 1,073 (37.8%) experienced 2,615 infections of any duration and 708 (24.9%) experienced 1,130 6MPIs. Infection with oncogenic HPV types significantly increased the risk of detecting CIN grade 2 or greater (CIN2+) versus non-oncogenic types. For 6MPI, the highest risk was associated with HPV-33 (hazard ratio [HR]: 31.9 [8.3-122.2, p < 0.0001]). The next highest risk was with HPV-16 (21.1 [6.3-70.0], p < 0.0001). Similar findings were seen for infections of any duration. Significant risk was also observed for HPV-18, HPV-31, and HPV-45. Concomitant HPV infection or CIN grade 1 or greater associated with a different oncogenic HPV type increased risk. Most women (79.3%) with an HPV infection at baseline cleared detectable infections of any duration, and 69.9% cleared a 6MPI. The risk of progression of HPV infection to CIN2+ in women >25 years in this study was similar to that in women 15-25 years in PATRICIA.

Efficacy of vitamin C vaginal tablets as prophylaxis for recurrent bacterial vaginosis: a randomised, double-blind, placebo-controlled clinical trial.

BACKGROUND: The aetiology of bacterial vaginosis (BV) is still unclear but it is currently considered to be a synergistic polymicrobial syndrome. BV can often arise as a chronic or recurrent disease. The reason for such recurrences is not well elucidated. Previous studies have suggested that vaginal vitamin C may be a useful treatment in reducing recurrence rate, by increasing vaginal acidification and thereby making up for the decrease in hydrogen peroxide that results from a reduction in the number of lactobacilli present. Based on the above-mentioned consideration, a study was performed that aimed to evaluate the effect of vitamin C in the prophylaxis of BV relapses. METHODS: This was a randomised, double-blind, placebo-controlled, parallel-group clinical trial. One hundred and forty-two women, after having been cured from a recent episode of BV by either metronidazole or clindamycin, were randomised to receive vitamin C (74 patients) or placebo (68 patients) as prophylaxis for six monthly cycles, starting within 24 hours of the determination of 'BV cure'. The patients applied one vaginal tablet once a day for 6 consecutive days per month after menses. RESULTS: The rate of BV recurrence during the first 3 months was considerably lower in the vitamin C group (6.8%) than in the placebo (14.7%) group. Considering a 6-month treatment period, the recurrence rate in the vitamin C group (16.2%) was significantly lower (P = 0.024) than in the placebo group (32.4%). Moreover, at the same time point, the survival analysis of Kaplan Meyer was significant in favour of the vitamin C group compared with the placebo group (P = 0.029). CONCLUSIONS: The study showed that regular use of 250 mg ascorbic acid vaginal tablets on 6 days per month for 6 months after successful treatment of bacterial vaginosis halves the risk of recurrence from 32.4% to 16.2% (P = 0.024).

Women's perceptions and reasons for choosing the pill, patch, or ring in the CHOICE study: a cross-sectional survey of contraceptive method selection after counseling.

BACKGROUND: The European CHOICE study was a cross-sectional survey that evaluated women's combined hormonal contraceptive choices before and after contraceptive counseling in Austria, Belgium, Czech Republic and Slovakia, the Netherlands, Poland, Sweden, Switzerland, Israel, Russia, and Ukraine. The changes in method selection before and after counseling were reported previously. In this paper we present the reasons given by the 18,787 participating women for selecting their contraceptive method of choice, as well as their perceptions about the contraceptive pill, patch, and ring after counseling. METHODS: Women with an interest in a combined hormonal contraceptive method (pill, patch, or ring) were counseled using a standardized counseling leaflet. The women completed questionnaires, which included questions on why they had selected a particular method of contraception, and the extent to which they agreed with statements about the attributes of the pill, patch, and ring. The results for each country were compared with the percentages for all countries combined by using a binomial regression model. Multiple logistic regression models were used to investigate the extent to which the probability of choosing a method was related to prespecified aspects (i.e. perceptions) of each contraceptive method. RESULTS: 'Easy to use', 'convenience', and 'regular menstrual bleeding' were important selection criteria. 'Nondaily administration' was one of the main reasons women selected the patch or ring. 'Daily use' and 'will forget to take it' were the primary reasons for not selecting the pill, while the main reasons for not choosing the patch included 'not discrete, visible' and 'can fall off'. In a small number of instances, the ring was rejected because some women don't like to use a 'foreign body'. Women's perceptions influenced their contraceptive decisions: positive perceptions about a method increased the likelihood that a woman would select it. After counseling, many women associated the pill with forgetfulness, and many still did not know about the patch or ring's key attributes. Women's knowledge about a particular method was generally greater if they had chosen it. CONCLUSIONS: To support informed contraceptive decision-making, healthcare professionals should realize that a woman's view of a method's ease of use is more important than perceived efficacy, tolerability, health benefits, or risks.

Effect of a levonorgestrel intrauterine system on women with type 1 diabetes: a randomized trial.

OBJECTIVE: Women with diabetes need safe, effective contraception. Although intrauterine devices provide superior contraception, concerns remain that progestin absorbed systemically from the levonorgestrel-releasing device may impair carbohydrate metabolism. To examine the effect of the levonorgestrel-releasing intrauterine system on glucose metabolism in diabetic women. METHODS: We randomly assigned 62 women with uncomplicated insulin-dependent diabetes mellitus to either a levonorgestrel-releasing or a copper T 380A intrauterine device. The primary outcome to assess glucose metabolism was glycosylated hemoglobin; fasting serum-glucose levels and daily insulin dose requirements over 12 months of observation were examined as well. RESULTS: Outcome data were available for 29 women using the levonorgestrel-releasing and 30 using the copper device. At 12 months, mean glycosylated levels were similar for women of the 2 groups (6.3%, standard deviation [SD] +/- 1.5 compared with 6.3%, SD +/- 1.3, respectively). The same was true for mean fasting-serum glucose levels (7.4 mM, SD +/- 4.2 compared with 7.5 mM, SD +/- 4.2) and daily insulin doses (35.1 units, SD +/- 12.8 compared with 36.4 units, SD +/- 9.0). No important differences were noted at either 6 weeks or 6 months. CONCLUSION: The levonorgestrel-releasing device had no adverse effect on glucose metabolism, even at the 6-week observation when systemic levels of levonorgestrel would have been higher than at later observations. Concern about a potential adverse effect of this contraceptive on glucose control is unwarranted, and its use in women with diabetes should be liberalized. LEVEL OF EVIDENCE: I.