Search

Background: The 12-week, randomized, double-blind, placebo-controlled, multicenter, phase 3 REJOICE trial demonstrated that TX-004HR, an investigational, applicator-free, low-dose vaginal softgel capsule containing solubilized 17 β-estradiol, effectively and rapidly treats symptoms of vulvar and vaginal atrophy (VVA) with negligible to very low systemic absorption. The aim of this analysis was to assess whether the efficacy of TX-004HR varies with age, body mass index (BMI), uterine status, pregnancy status, and vaginal delivery. Methods: The REJOICE trial evaluated the efficacy of 4-, 10-, and 25- μg doses of TX-004HR in postmenopausal women (40-75 years) with VVA and a self-identified most bothersome symptom of moderate-to-severe dyspareunia. Prespecified subgroup analyses of the four co-primary endpoints (percentages of superficial cells and parabasal cells, vaginal pH, and severity of dyspareunia) were analyzed with respect to age, BMI, uterine status, pregnancy status, and vaginal births. Each dose was compared with placebo for change from baseline to week 2 through week 12, respectively. Results: TX-004HR significantly improved superficial cells, parabasal cells, and vaginal pH from baseline to weeks 2 and 12 in most subgroups. All TX-004HR doses numerically reduced the severity of dyspareunia by 2 weeks and maintained efficacy over 12 weeks, with many of the subgroups having statistically significant improvement relative to placebo. Conclusions: TX-004HR was efficacious for treating symptomatic VVA, and it demonstrated a consistency of effect when women's age, BMI, uterine status, pregnancy status, and vaginal births were evaluated. Clinical Trial Identifier: NCT02253173. [ABSTRACT FROM AUTHOR]

The purpose of this paper is to provide evidence-based guidance on the management of a positive human papilloma virus (HPV) test and to provide guidance around screening and HPV testing for specific patient populations. The guideline was developed by a working group in collaboration with the Gynecologic Oncology Society of Canada (GOC), Society of Colposcopists of Canada (SCC), and the Canadian Partnership Against Cancer. The literature informing these guidelines was obtained through a systematic review of relevant literature by a multi-step search process led by an information specialist. The literature was reviewed up to July 2021 with manual searches of relevant national guidelines and more recent publications. The quality of the evidence and strength of recommendations were developed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. The intended users of this guideline include primary care providers, gynecologists, colposcopists, screening programs, and healthcare facilities. The implementation of the recommendations will ensure an optimum implementation of HPV testing with a focus on the management of positive results. Recommendations for appropriate care for underserved and marginalized groups are made. [ABSTRACT FROM AUTHOR]

The article examines the safety and efficacy of transdermal estradiol gel, aiming to identify the lowest effective dose for the treatment of vasomotor and vulvovaginal atrophy symptoms in postmenopausal women. The study also examined the changes from baseline in hot flush frequency and severity at four and 12 weeks and changes from baseline in vaginal atrophy symptoms at 12 weeks. The 0.87 g/d of estradiol gel was well tolerated and produced no unexpected adverse effects.

Objectives: To evaluate tolerability and safety of estetrol (E4) 15 mg/drospirenone (DRSP) 3 mg oral contraceptive using pooled data from two, multicenter, phase 3 trials.Study Design: The two trials enrolled participants aged 16-50 years with a body mass index ≤35.0 kg/m2 to use E4/DRSP in a 24/4-day regimen for up to 13 cycles. We pooled data from participants who used at least one E4/DRSP dose and had a follow-up assessment to analyze adverse events (AEs), vital signs, and laboratory parameters, including serum lipids, glucose, glycated hemoglobin, and potassium. We consolidated similar Medical Dictionary for Regulatory Activities preferred terms into groupings.Results: Of 3725 participants enrolled, we included 3417 in the analyses of whom 1786 (52.3%) reported ≥1 AE. Most participants with reported AEs had AEs that investigators rated as mild or moderate (n = 1665, 93.2%); of participants reporting AEs, 1105 (61.9%) did so during cycles 1 to 3. In total, 981 (28.7%) participants experienced ≥1 treatment-related AE, most frequently related to bleeding complaints (n = 323, 9.5%), breast pain or tenderness (n = 136, 4.0%), acne (n = 113, 3.3%), and mood disturbance (n = 111, 3.2%). Discontinuation due to treatment-related AEs occurred in 272 participants (8.0%), with only bleeding complaints (n = 97, 2.8%) and mood disturbance (n = 38, 1.1%) at rates exceeding 1%. Three participants experienced serious AEs, which the site investigators considered treatment-related: one venous thromboembolism, one worsening of depression, and one ectopic pregnancy. We found no clinically relevant changes in weight, blood pressure, heart rate, or laboratory parameters during treatment.Conclusions: E4/DRSP is associated with a favorable tolerability and safety profile.Implications Statement: Pooling data allowed for a robust assessment of tolerability and safety, including relatively infrequent events. Other than bleeding complaints and mood disturbance, no adverse event resulted in E4/DRSP discontinuation at rates >1%. Post-marketing surveillance studies are needed to evaluate long-term safety of the E4/DRSP COC and population-based venous thromboembolism risks. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the bleeding patterns of a new combined oral contraceptive containing estetrol (E4) 15 mg/drospirenone (DRSP) 3 mg in a 24/4-day regimen.Study Design: We pooled bleeding data from two parallel, open-label, 13-cycle phase 3 trials that enrolled participants 16 to 50 years old with body mass index (BMI) ≤35 kg/m2. Participants reported vaginal bleeding/spotting in daily diaries. For this bleeding analysis, we included participants with at least one evaluable cycle. We calculated mean frequencies of scheduled and unscheduled bleeding/spotting episodes and median duration of bleeding/spotting episodes, and assessed associations between treatment compliance, BMI and recent hormonal contraceptive use on bleeding/spotting outcomes.Results: We included 3409 participants with 33,815 cycles. Scheduled bleeding/spotting occurred in 87.2% to 90.4% of participants/cycle, with a median duration of 4 to 5 days. Unscheduled bleeding/spotting decreased from 27.1% in Cycle 1 to 20.6% in Cycle 2 to ≤17.5% from Cycle 5 onwards. Most (66.5%) unscheduled bleeding/spotting episodes were spotting-only. Between 5.8% and 7.8% of users/cycle experienced absence of any scheduled or unscheduled bleeding/spotting. Missing one or more active pills resulted in a higher occurrence of unscheduled bleeding/spotting (adjusted odds ratio [aOR] 2.13 [95% confidence interval 1.68-2.70]) and absence of scheduled bleeding/spotting (aOR 2.36 [1.82-3.07]). Participants with a BMI ≥30 kg/m2 reported more absence of scheduled bleeding/spotting (aOR 1.68 [1.37-2.05]). Switchers and starters reported similar frequencies of unscheduled bleeding/spotting (aOR 0.94 [0.83-1.07]) and absence of scheduled bleeding/spotting (aOR 1.00 [0.85-1.19]). Three percent of participants discontinued for a bleeding-related adverse event.Conclusion: E4/DRSP use results in a predictable bleeding pattern with limited unscheduled bleeding/spotting. Noncompliance and BMI affect bleeding patterns.Implications Statement: Most estetrol/drospirenone users experience a predictable and regular bleeding pattern. Providers can educate patients about the expected bleeding patterns and should advise users that they may infrequently experience no scheduled bleeding/spotting. This information may improve user acceptability and continuation of this new oral contraceptive. [ABSTRACT FROM AUTHOR]

Background: Infections with human papillomavirus (HPV) types 16 and 18 account for ~70% of invasive cervical cancers but the degree of protection from naturally acquired anti‐HPV antibodies is uncertain. We examined the risk of HPV infections as defined by HPV DNA detection and cervical abnormalities among women >25 years in the Human Papilloma VIrus Vaccine Immunogenicity ANd Efficacy trial's (VIVIANE, NCT00294047) control arm. Methods: Serum anti‐HPV‐16/18 antibodies were determined at baseline and every 12 months in baseline DNA‐negative women (N = 2687 for HPV‐16 and 2705 for HPV‐18) by enzyme‐linked immunosorbent assay (ELISA) from blood samples. HPV infections were identified by polymerase chain reaction (PCR) every 6‐months, and cervical abnormalities were confirmed by cytology every 12 months. Data were collected over a 7‐year period. The association between the risk of type‐specific infection and cervical abnormalities and serostatus was assessed using Cox proportional hazard models. Results: Risk of newly detected HPV‐16‐associated 6‐month persistent infections (PI) (hazard ratio [HR] = 0.56 [95%CI:0.32; 0.99]) and atypical squamous cells of undetermined significance (ASC‐US+) (HR = 0.28 [0.12; 0.67]) were significantly lower in baseline seropositive vs baseline seronegative women. HPV‐16‐associated incident infections (HR = 0.81 [0.56; 1.16]) and 12‐month PI (HR = 0.53 [0.24; 1.16]) showed the same trend. A similar trend of lower risk was observed in HPV‐18‐seropositive vs ‐seronegative women (HR = 0.95 [0.59; 1.51] for IIs, HR = 0.43 [0.16; 1.13] for 6‐month PIs, HR = 0.31 [0.07; 1.36] for 12‐month PIs, and HR = 0.61 [0.23; 1.61] for ASC‐US+). Conclusions: Naturally acquired anti‐HPV‐16 antibodies were associated with a decreased risk of subsequent infection and cervical abnormalities in women >25 years. This possible protection was lower than that previously reported in 15‐ to 25‐year‐old women. [ABSTRACT FROM AUTHOR]

The article discusses the findings of a randomized study to determine the efficacy of the 9-valent human papillomavirus (9vHPV) vaccine in women 16 to 26 years of age. Topics include the pathology of HPV and efforts to prevent HPV-related diseases through prophylactic vaccines. The study concluded that 9vHPV vaccine is effective in preventing infection and disease related to HPV-31, 33, 45, 52, and 58 in susceptible subjects.

Background: The efficacy and safety of testosterone treatment for hypoactive sexual desire disorder in postmenopausal women not receiving estrogen therapy are unknown. Methods: We conducted a double-blind, placebo-controlled, 52-week trial in which 814 women with hypoactive sexual desire disorder were randomly assigned to receive a patch delivering 150 or 300 µg of testosterone per day or placebo. Efficacy was measured to week 24; safety was evaluated over a period of 52 weeks, with a subgroup of participants followed for an additional year. The primary end point was the change from baseline to week 24 in the 4-week frequency of satisfying sexual episodes. Results: At 24 weeks, the increase in the 4-week frequency of satisfying sexual episodes was significantly greater in the group receiving 300 µg of testosterone per day than in the placebo group (an increase of 2.1 episodes vs 0.7, p < 0.001) but not in the group receiving 150 µg per day (1.2 episodes, p = 0.11). As compared with placebo, both doses of testosterone were associated with significant increases in desire (300 µg per day, p < 0.001; 150 µg per day, p = 0.04) and decreases in distress (300 µg per day, p < 0.001; 150 µg per day, p = 0.04). The rate of androgenic adverse events --primarily unwanted hair growth-- was higher in the group receiving 300 µg of testosterone per day than in the placebo group (30.0% vs23.1%). Breast cancer was diagnosed in four women who received testosterone (as compared with none who received placebo); one of the four received the diagnosis in the first 4 months of the study period, and one, in retrospect, had symptoms before undergoing randomization. Conclusions: In postmenopausal women not receiving estrogen therapy, treatment with a patch delivering 300 µg of testosterone per day resulted in a modest but meaningful improvement in sexual function. The long-term effects of testosterone, including effects on the breast, remain uncertain. [ABSTRACT FROM AUTHOR]

The Profile of Female Sexual Function (PFSF) is a patient-based instrument for the measuring of loss of sexual function in menopausal women with low libido (hypoactive female sexual desire disorder). The instrument, which contains 37 items in seven domains (sexual desire, arousal, orgasm, sexual pleasure, sexual concerns, sexual responsiveness, and sexual self-image) and a single-item measure of overall satisfaction with sexuality, has been extensively developed and initially validated in over 500 oophorectomized women with low libido in North America, Europe, and Australia. Initial validation results showed the PFSF is capable of discriminating these patients from age-matched controls and produced consistent responses and sensitivity across geographies. The objective of this nonrandomized, parallel-group study was to examine the psychometric properties of the final PFSF in an independent group of surgically menopausal women with low libido and to extend validation to naturally menopausal women with low libido. Participants from 16 study centers in North America included surgically ( n = 59) and naturally ( n = 88) menopausal women with low libido and their age-matched control subjects, both premenopausal ( n = 57) and naturally menopausal ( n = 47), who reported no problems with libido. Subjects completed the PFSF at baseline and again 4 weeks later. Adjusted mean scores for each of the seven domains were statistically significantly lower ( P < 0.0001) in surgically menopausal women with low libido compared with age-matched control women, and in naturally menopausal women with low libido compared with naturally menopausal control women, demonstrating excellent discriminant validity. Test-retest reliability ranged from 0.57 to 0.91 for the seven domain scores, whereas internal-consistency reliability ranged from 0.74 to 0.95. Results of this research support the conclusion that the PFSF is a valid and reliable instrument for measurement of loss of sexual function in both naturally and surgically menopausal women with low libido. [ABSTRACT FROM AUTHOR]