Efficacy and Safety of Single Oral Dosing of Secnidazole for Trichomoniasis in Women: Results of a Phase 3, Randomized, Double-Blind, Placebo-Controlled, Delayed-Treatment Study.

BACKGROUND: Trichomonas vaginalis is the most prevalent nonviral sexually transmitted infection. We evaluated the efficacy and safety of secnidazole vs placebo in women with trichomoniasis. METHODS: Women with trichomoniasis, confirmed by a positive T. vaginalis culture, were randomized to single-dose oral secnidazole 2 g or placebo. The primary endpoint was microbiological test of cure (TOC) by culture 6-12 days after dosing. At the TOC visit, participants were given the opposite treatment. They were followed for resolution of infection afterward and offered treatment at subsequent visits, if needed. Fifty patients per group (N = 100) provided approximately 95% power to detect a statistically significant difference between treatment groups. RESULTS: Between April 2019 and March 2020, 147 women enrolled at 10 sites in the United States. The modified intention-to-treat (mITT) population included 131 randomized patients (secnidazole, n = 64; placebo, n = 67). Cure rates were significantly higher in the secnidazole vs placebo group for the mITT population (92.2% [95% confidence interval {CI}: 82.7%-97.4%] vs 1.5% [95% CI: .0%-8.0%]) and for the per-protocol population (94.9% [95% CI: 85.9%-98.9%] vs 1.7% [95% CI: .0%-8.9%]). Cure rates were 100% (4/4) in women with human immunodeficiency virus (HIV) and 95.2% (20/21) in women with bacterial vaginosis (BV). Secnidazole was generally well tolerated. The most frequently reported treatment-emergent adverse events (TEAEs) were vulvovaginal candidiasis and nausea (each 2.7%). No serious TEAEs were observed. CONCLUSIONS: A single oral 2 g dose of secnidazole was associated with significantly higher microbiological cure rates vs placebo, supporting a role for secnidazole in treating women with trichomoniasis, including those with HIV and/or BV. CLINICAL TRIALS REGISTRATION: NCT03935217.

Long-Term Safety and Efficacy of Fractional CO2 Laser Treatment in Post-Menopausal Women with Vaginal Atrophy.

BACKGROUND AND AIM: We have previously reported improvement of clinical symptoms of genitourinary syndrome of menopause (GSM) at 3 and 6 months following three CO2 laser treatments. The current paper presents the results of long term follow up at 12, 15- and 18-months post laser treatment. METHODS: Twenty subjects (mean age 60.65 ± 6.34 years) who had completed the core study participated in follow-up. Subjects were evaluated at 12, 15, and 18 months following final laser therapy. An optional maintenance treatment was offered during Month 12 and Month 15 to those women who failed to increase their Vaginal Health Index Score (VHIS) by more than 34% from their individual baseline, or if the subject desired an additional treatment. At each study visit, VHIS and vulvovaginal atrophy (VVA) symptom severity were recorded. Sexual function was assessed using the Female Sexual Function Index (FSFI). RESULTS: Fifteen subjects were eligible for a single maintenance treatment (N = 2, at 12 months, and N = 13 at 15 Months). The mean VHIS (± standard deviation) remained significantly improved at 12 months following their last laser treatment (16.3 ± 4.5 vs. Baseline 12.4 ± 4.0; p < 0.05) and at the 15- and 18-months follow up visits as well (16.9 ± 4.6 and 17.1 ± 4.6, respectively; p < 0.05 compared to Baseline). Almost all VVA symptoms were significantly improved at 12 months following the third treatment compared to Baseline and this improvement was sustained at 15 and 18 months. At the 12 Months visit, the total FSFI score increased significantly (N = 15, 24.4 ± 6.9; p < 0.05), and at the 15- and 18-month follow-up visits, the total FSFI remained significantly higher than Baseline (22.2 ± 6.7, 25.8 ± 6.6). CONCLUSION: Fractional CO2 laser treatments are effective in alleviating symptoms of VVA and sexual dysfunction in post-menopausal women, and that effects are sustained over the long-term.

Early effect of fractional CO2 laser treatment in Post-menopausal women with vaginal atrophy.

BACKGROUND AND AIM: Fractional CO2 lasers have been shown to provide improvement of vulvovaginal atrophy (VVA). The aim of the current study was to assess the early effect of a fractional CO2 laser system in treating postmenopausal women with clinical symptoms of VVA. METHODS: 28 healthy post-menopausal women (mean age 60.1 ± 5.55 years) with VVA-related symptoms were treated with fractional CO2 laser 3 times, in 4-week intervals. At each study visit, VHIS score and VVA symptom severity were recorded. Sexual function was assessed with the Female Sexual Function Index (FSFI). RESULTS: One month following the first laser treatment, the mean VHIS score was significantly improved (13.89 ± 4.25 vs. baseline 11.93 ± 3.82; p < 0.05), and improved further at 3 and 6 months following all three laser treatments (16.43 ± 4.20 and 17.46 ± 4.07, respectively). Almost all VVA symptoms were significantly improved at one month following the first treatment. A further significant improvement in VVA symptoms was noted at 3 and 6 months following the third laser treatment. Following treatments, the FSFI score increased significantly (22.36 ± 10.40 vs. baseline 13.78 ± 7.70; p < 0.05), and remained significantly higher than baseline at the 3- and 6-month follow-up visits. CONCLUSION: CO2 laser therapy for post-menopausal women can be considered an effective therapeutic option providing relief of symptoms already noted after one laser treatment.

Role of female intimate hygiene in vulvovaginal health: Global hygiene practices and product usage.

Women use various feminine hygiene products, often as part of their daily cleansing routine; however, there is a paucity of published medical literature related to the external vulva and how personal hygiene practices can affect it. This review article provides background information on the physiological changes that occur during women's lives and reviews the relevance of transient and resident microbiota as they relate to common vaginal and vulvar disorders. It also discusses the need for female intimate hygiene, common practices of feminine hygiene from a global perspective, and the potential benefits of using suitable external, topical feminine vulvar washes to minimize the risk of vulvovaginal disorders and to improve overall intimate health in women around the world. Supported by international guidelines, daily gentle cleansing of the vulva is an important aspect of feminine hygiene and overall intimate health. Women should be encouraged to choose a carefully formulated and clinically tested external wash that provides targeted antimicrobial and other health benefits without negatively impacting on the natural vulvovaginal microbiota.

Ospemifene: a novel selective estrogen receptor modulator for treatment of dyspareunia.

Ospemifene is a novel, oral selective estrogen receptor modulator that has been approved in the USA for treatment of dyspareunia. The decline in estrogen during menopause creates vulvovaginal changes that can cause symptoms that adversely impact women psychosexually. Many women are reluctant to discuss painful sex and providers must proactively inquire about sexuality issues. Ospemifene has been shown to reverse changes associated with vulvovaginal atrophy and relieve symptoms of dyspareunia. Safety studies of treatment up to 52 weeks have shown ospemifene to be safe with no impact on endometrial hyperplasia/carcinoma, venous thrombotic events or pelvic organ prolapse. Further studies are needed to evaluate its role in bone and breast health.

Evaluation of the EmbaGYN™ pelvic floor muscle stimulator in addition to Kegel exercises for the treatment of female stress urinary incontinence: a prospective, open-label, multicenter, single-arm study.

AIM: To assess the efficacy and safety of the EmbaGYN™ Pelvic Floor Exerciser, a battery-powered neuromuscular stimulation device with a vaginal, two-electrode stimulation probe in women with stress urinary incontinence. MATERIALS & METHODS: In this prospective, open-label, multicenter, single-arm study, patients with stress urinary incontinence (n = 83) underwent 12 weeks of treatment with EmbaGYN with Kegel exercises. RESULTS: At week 12, the mean number of incontinence episodes/day (primary end point) fell 56.2% (p = 0.152). A ≥50% decrease from baseline in incontinence episodes was seen in 65.3% of subjects (p = 0.006). The mean number of incontinence pads/day fell 57.1% (p = 0.001). Mean 24- and 1-h in-office urine loss declined 59.0% (p < 0.001) and 67% (p = 0.019), respectively. There was one nonserious device-related adverse event. CONCLUSION: EmbaGYN with Kegel exercises resulted in significant reductions in urine loss, incontinence pad use and improved incontinence-related quality of life, but did not have a significant effect on incontinence episodes/day.

Efficacy and safety of oral tranexamic acid in women with heavy menstrual bleeding and fibroids.

AIM: To evaluate the efficacy and safety of oral, modified-release tranexamic acid in women with heavy menstrual bleeding and fibroids. MATERIALS & METHODS: This was a pooled analysis of two pivotal Phase III studies. Fibroids were evaluated by transvaginal ultrasonography. Menstrual blood loss (MBL) was measured via a validated alkaline hematin method. RESULTS: In women with and without fibroids, mean MBL was reduced compared with placebo across all treatment cycles (p < 0.001). Within the tranexamic acid group, more statistically significant (p < 0.001) reductions in MBL compared with placebo occurred in women with fibroids than in those without fibroids. Adverse events were similar between treatment groups. CONCLUSION: Tranexamic acid was well tolerated and reduced MBL in women with and without fibroids.

Daily menstrual blood loss and quality of life in women with heavy menstrual bleeding.

AIM: Excessive blood loss during menstruation is a major problem for women of reproductive age. Women who experience heavy menstrual bleeding (HMB) often present to physicians because of the subsequent negative impact HMB has on their daily lives and activities. The objective of this post-hoc analysis is to evaluate daily menstrual blood loss (MBL) in women with HMB and assess the relationship between daily MBL and women's perceptions of MBL, limitations in physical activities and limitations in social/leisure activities as measured by the Menorrhagia Impact Questionnaire. MATERIALS & METHODS: Data from two randomized, placebo-controlled studies of an oral tranexamic acid formulation in women with HMB were assessed. Daily MBLs and Menorrhagia Impact Questionnaire scores were evaluated for two pretreatment cycles and the first three tranexamic acid treatment cycles of each study. Effect-size analyses were not conducted. RESULTS & CONCLUSION: Highest daily MBLs occurred on days 2 and 3 of menstrual cycles. Women's perceptions of daily MBL were consistent with objective measures of MBL. Higher daily MBL was related to increased limitations in physical activities and limitations in social/leisure activities. Daily MBL values were consistent with women's perceptions of MBL. Reduced daily MBL was associated with improvements in health-related quality of life.

Evaluation of a new, rapid test for detecting HCV infection, suitable for use with blood or oral fluid.

The availability of a highly accurate, rapid, point-of-care test for hepatitis C virus (HCV) may be useful in addressing the problem of under-diagnosis of HCV, by increasing opportunities for testing outside of traditional clinical settings. A new HCV rapid test device (OraQuick® HCV Rapid Antibody Test), approved recently in Europe for use with venous blood, fingerstick blood, serum, plasma, or oral fluid was evaluated in a multi-center study and performance compared to established laboratory-based tests for detection of HCV. The HCV rapid test was evaluated in prospective testing of subjects with signs and/or symptoms of hepatitis, or who were at risk for hepatitis C using all 5 specimen types. Performance was assessed relative to HCV serostatus established by laboratory methods (EIA, RIBA and PCR) approved in Europe for diagnosis of hepatitis C infection. Sensitivity to antibody in early infection was also compared to EIA in 27 seroconversion panels. In addition, the reliability of the oral fluid sample for accurate detection of anti-HCV was assessed by studying the impact of various potentially interfering conditions of oral health, use of oral care products and consumption of food and drink. In this large study of at-risk and symptomatic persons, the overall specificities of the OraQuick® HCV Rapid Antibody Test were equivalent (99.6-99.9%) for all 5 specimen types and the 95% CIs substantially overlapped. Overall sensitivities were virtually identical for venous blood, fingerstick blood, serum and plasma (99.7-99.9%). Observed sensitivity was slightly lower for oral fluid at 98.1% though the upper CI (99.0%) was equal to the lower CI for venous blood and fingerstick blood. Most of the HCV positive subjects which gave nonreactive results in oral fluid had serological and virological results consistent with resolved infection. Sensitivity for anti-HCV in early seroconversion was virtually identical between the HCV rapid test and EIA. Detection of anti-HCV in oral fluid appeared generally robust to conditions of oral health, consumption of food and drink and use of oral care products. The OraQuick® HCV Rapid Antibody Test demonstrated clinical performance that was equivalent to current laboratory-based EIA. This new, HCV rapid test appears suitable as an aid in the diagnosis of HCV infection and may increase testing opportunities due to its simplicity and flexibility to use multiple specimen types, including fingerstick blood and oral fluid.

Tranexamic acid treatment for heavy menstrual bleeding: a randomized controlled trial.

OBJECTIVE: To assess the efficacy and safety of an oral formulation of tranexamic acid for the treatment of heavy menstrual bleeding. METHODS: Adult women with heavy menstrual bleeding (mean menstrual blood loss 80 mL or more per cycle) were enrolled in a double-blind, placebo-controlled study. After two pretreatment menstrual cycles, women were randomized to receive tranexamic acid 3.9 g/d or placebo for up to 5 days per menstrual cycle through six cycles. To meet the prespecified three-component primary efficacy end point, mean reduction in menstrual blood loss from baseline with tranexamic acid treatment needed to be 1) significantly greater than placebo, 2) greater than 50 mL, and 3) greater than a predetermined meaningful threshold (36 mL or higher). Health-related quality of life was measured using a validated patient-reported outcome instrument. RESULTS: Women who received tranexamic acid (n=115) met all three primary efficacy end points: first, a significantly greater reduction in menstrual blood loss of -69.6 mL (40.4%) compared with -12.6 mL (8.2%) in the 72 women who received placebo (P<.001); reduction of menstrual blood loss exceeding a prespecified 50 mL; and last, reduction of menstrual blood loss considered meaningful to women. Compared with women receiving placebo, women treated with tranexamic acid experienced significant improvements in limitations in social or leisure and physical activities, work inside and outside the home, and self-perceived menstrual blood loss (P<.01). The majority of adverse events were mild to moderate in severity, and the incidence of gastrointestinal adverse events was comparable with placebo. CONCLUSION: In this study, a new oral tranexamic acid treatment was well tolerated and significantly improved both menstrual blood loss and health-related quality of life in women with heavy menstrual bleeding. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00386308. LEVEL OF EVIDENCE: I.

The effect of extending the pill-free interval on follicular activity: triphasic norgestimate/35 micro g ethinyl estradiol versus monophasic levonorgestrel/20 micro g ethinyl estradiol.

This study was designed to evaluate follicular activity in women taking oral contraceptives with imposed imperfect compliance. After completing a 28-day cycle of either triphasic norgestimate/EE (NGM/EE) (Ortho Tri-Cyclen, Ortho-McNeil Pharmaceutical, Raritan, NJ) or monophasic levonorgestrel/EE (LNG/EE) (Alesse, Wyeth-Ayerst Laboratories, Philadelphia, PA), women were instructed to intentionally "miss" the first two active pills of the next pack. The first two tablets in the second treatment cycle were deliberately omitted, thereby extending the pill-free interval from 7 days to 9 days. Subjects were randomized to take NGM/EE (n = 40) or LNG/EE (n = 39) for two consecutive cycles. The mean maximum follicular diameter was significantly greater in women taking LNG/EE than in those taking NGM/EE (16.4 +/- 7.1 mm vs. 12.6 +/- 8.3 mm, p = 0.047). The LNG/EE group had significantly higher median serum estradiol concentrations compared to women taking NGM/EE on pill Days 10 [29.5 pg/mL (range: 10.0-540.0 pg/mL) vs. 2.5 pg/mL (range: 2.0-6.0 pg/mL), p < 0.001] and 14 [11.0 pg/mL (range: 2.0-416.0 pg/mL) vs. 2.0 pg/mL (range: 2.0-3.0 pg/mL), p = 0.001]. Two women in the NGM/EE group and three women in the LNG/EE group had at least one progesterone level > or =3 ng/mL; none of these women demonstrated a maximum follicular diameter >13 mm. Significantly greater follicular activity was observed after an extended pill-free interval in women taking LNG/EE compared to those taking triphasic NGM/EE. The clinical implications of these findings require further study.