Effects of E4/DRSP on self-reported physical and emotional premenstrual and menstrual symptoms: data from the phase 3 clinical trial in Europe and Russia.

PURPOSE: To describe the effects of estetrol (E4) 15 mg/drospirenone (DRSP) 3 mg on physical and emotional premenstrual and menstrual symptoms. MATERIALS AND METHODS: We used Menstrual Distress Questionnaire (MDQ) data from a phase-3 trial (NCT02817828) in Europe and Russia with participants (18 - 50 years) using E4/DRSP for up to 13 cycles. We assessed mean changes in MDQ-t-scores from baseline to end of treatment in premenstrual (4 days before most recent flow) and menstrual (most recent flow) scores for 4 MDQ domains in starters and switchers (use of hormonal contraception in prior 3 months) and performed a shift analysis on individual symptoms within each domain. RESULTS: Of 1,553 treated participants, 1,398(90.0%), including 531(38%) starters, completed both MDQs. Starters reported improvements for premenstrual Pain (-1.4), Water Retention (-3.3) and Negative Affect (-2.5); and for menstrual Pain (-3.5), Water Retention (-3.4), and Negative Affect (-2.7) (all p < 0.01). For switchers, no changes were significant except an increase in premenstrual (+1.0, p = 0.02) and menstrual (+1.5, p = 0.003) Water Retention. We observed a change in symptom intensity in >40% of participants for Cramps, Backache and Fatigue (domain Pain), Painful or Tender Breast and Swelling (domain Water Retention) and Mood Swings and Irritability (domain Negative Affect). CONCLUSION: E4/DRSP starters experienced significant improvements in the domains Pain, Water Retention and Negative Affect particularly benefiting those with more severe baseline symptoms. Switchers showed minimal changes.

A phase 3 study in Europe and Russia showed that Estetrol/Drospirenone, a new combined oral contraceptive, significantly improved the MDQ scores for domains Pain, Water Retention and Negative Affect in women starting COC use, while switchers showed minimal changes.

Directive clinique no 422b : Ménopause et santé génito-urinaire.

OBJECTIF: Proposer des stratégies fondées sur les plus récentes données publiées pour améliorer les soins aux femmes ménopausées ou en périménopause. POPULATION CIBLE: Les femmes ménopausées ou en périménopause. BéNéFICES, RISQUES ET COûTS: La population cible bénéficiera des plus récentes données scientifiques publiées communiquées par leurs fournisseurs de soins de santé. Aucun coût ni préjudice ne sont associés à cette information, car les femmes seront libres de choisir parmi les différentes options thérapeutiques, y compris le statu quo, pour la prise en charge des symptômes et morbidités associés à la ménopause. DONNéES PROBANTES: Les auteurs ont interrogé les bases de données PubMed, MEDLINE et Cochrane Library pour extraire des articles publiés entre 2002 et 2020 en utilisant des termes MeSH spécifiques à chacun des sujets abordés dans les 7 chapitres. MéTHODES DE VALIDATION: Les auteurs ont évalué la qualité des données probantes et la force des recommandations en utilisant l'approche d'évaluation, de développement et d'évaluation (GRADE). Voir l'annexe A en ligne (tableau A1 pour les définitions et tableau A2 pour l'interprétation des recommandations fortes et conditionnelles [faibles]). PROFESSIONNELS CONCERNéS: gynécologues, obstétriciens, médecins de famille, internistes, urgentologues, infirmières (autorisées et praticiennes), pharmaciens, stagiaires (étudiants en médecine, résidents, moniteurs cliniques) et autres fournisseurs de soins de santé pour la population cible. DÉCLARATIONS SOMMAIRES: RECOMMANDATIONS.

Guideline No. 422b: Menopause and Genitourinary Health.

OBJECTIVE: Provide strategies for improving the care of perimenopausal and postmenopausal women based on the most recent published evidence. TARGET POPULATION: Perimenopausal and postmenopausal women. BENEFITS, HARMS, AND COSTS: Target population will benefit from the most recent published scientific evidence provided via the information from their health care provider. No harms or costs are involved with this information since women will have the opportunity to choose among the different therapeutic options for the management of the symptoms and morbidities associated with menopause, including the option to choose no treatment. EVIDENCE: Databases consulted were PubMed, MEDLINE, and the Cochrane Library for the years 2002-2020, and MeSH search terms were specific for each topic developed through the 7 chapters. VALIDATION METHODS: The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See online Appendix A (Tables A1 for definitions and A2 for interpretations of strong and weak recommendations). INTENDED AUDIENCE: physicians, including gynaecologists, obstetricians, family physicians, internists, emergency medicine specialists; nurses, including registered nurses and nurse practitioners; pharmacists; medical trainees, including medical students, residents, fellows; and other providers of health care for the target population. SUMMARY STATEMENTS: RECOMMENDATIONS.

International Anal Neoplasia Society Guidelines for the Practice of Digital Anal Rectal Examination.

OBJECTIVE: The aim of the study was to develop recommended techniques and quality assurance metrics for the practice of Digital Anal Rectal Examination (DARE). MATERIALS AND METHODS: The International Anal Neoplasia Society undertook a literature review and, using the AGREE II technique, developed guidelines for performing DARE. RESULTS: A consensus was formed regarding the optimum conditions and characteristics of DARE. Several Quality Assurance metrics were developed. CONCLUSIONS: Digital Anal Rectal Examination is a cheap and potentially universally available technique, which has the potential to facilitate the early diagnosis of anal cancers, when they are most amenable to treatment. These guidelines provide a basis for teaching the technique and may be used as for evaluation research.

Age at last screening and remaining lifetime risk of cervical cancer in older, unvaccinated, HPV-negative women: a modelling study.

BACKGROUND: There is a paucity of empirical evidence to inform the age at which to stop cervical cancer screening. The recommended age to stop screening generally varies between age 50-70 years worldwide. However, cervical cancer incidence and mortality remain high in older women. We used a Markov model of cervical cancer screening to estimate the remaining lifetime risk of cervical cancer at different ages and with different exit screening tests, with the aim of informing recommendations of the age at which to stop cervical cancer screening in developed countries. METHODS: For this modelling study, we developed a state transition (Markov) model of cervical cancer natural history and screening. We developed, calibrated, and validated our model using Canadian provincial registries and survey data. To simulate an age-structured population in the model, a new cohort of 236 564 women (one fifth of the population of Canadian women aged 20-24 years in 2012) entered the model every year and were successively modelled in parallel. Successive cohorts entered the model at age 10 years, creating an age-structured population of women aged 10-100 years. Women who had a total hysterectomy were excluded from the analyses. We calibrated our model to human papillomavirus (HPV) infection and cancer incidence with data from Statistics Canada, which compiles the data from 13 individual provincial registries. We chose a three-stage progressive cervical intraepithelial neoplasia model to include differences in management and treatment decisions depending on lesion severity. We modelled infections with four high-risk HPV groups: HPV16 and HPV18; HPV31, HPV33, HPV45, HPV52, and HPV58; HPV35, HPV39, HPV51, HPV56, HPV59, HPV66, and HPV68; and a generic group of other potentially oncogenic HPVs. We estimated 5-year, 10-year, and remaining lifetime risk of cervical cancer for older, unvaccinated women who stopped screening at different ages and underwent different screening tests. FINDINGS: Cervical cancer incidence excluding women with hysterectomies underestimated the incidence of cervical cancer in women with a cervix by up to 71% in women aged 80-84 years. Our model predicted that women without HPV vaccination who have been never screened have a 1 in 45 (95% percentile interval 1 in 32 to 1 in 64) lifetime risk of cervical cancer. Perfect adherence (100% of women screened) to cytology screening every 3 years between the ages of 25 years and 69 years could reduce the lifetime risk of cervical cancer to 1 in 532 women (95% percentile interval 1 in 375 to 1 in 820) without HPV vaccination. Increasing the age at which women stopped cytology screening from 55 years to 75 years led to incremental decreases in cancer risk later in life. A 70-year old woman whose screening history was unknown had an average remaining lifetime risk of 1 in 588 (<1%; 95% percentile interval 1 in 451 to 1 in 873) if she stopped screening. Her remaining lifetime risk at age 70 years was reduced to 1 in 1206 (2·0 times reduction; 95% percentile interval 1 in 942 to 1 in 1748) if she had a negative cytology test, 1 in 6525 (12·9 times reduction; 95% percentile interval 1 in 3167 to 1 in 18 664) if she had a negative HPV test, and 1 in 9550 (18·1 times reduction; 95% percentile interval 1 in 4928 to 1 in 23 228) if she had a negative co-test for cytology and HPV. INTERPRETATION: Cervical cancer risk reductions might be achieved by screening with cytology up to age 75 years, although with diminishing returns. A negative exit oncogenic HPV test or negative HPV test plus cytology correlates with a low remaining lifetime cervical cancer risk for unvaccinated women with a cervix after the age of 55 years. FUNDING: Canadian Institutes of Health Research.

A 9-valent HPV vaccine against infection and intraepithelial neoplasia in women.

BACKGROUND: The investigational 9-valent viruslike particle vaccine against human papillomavirus (HPV) includes the HPV types in the quadrivalent HPV (qHPV) vaccine (6, 11, 16, and 18) and five additional oncogenic types (31, 33, 45, 52, and 58). Here we present the results of a study of the efficacy and immunogenicity of the 9vHPV vaccine in women 16 to 26 years of age. METHODS: We performed a randomized, international, double-blind, phase 2b-3 study of the 9vHPV vaccine in 14,215 women. Participants received the 9vHPV vaccine or the qHPV vaccine in a series of three intramuscular injections on day 1 and at months 2 and 6. Serum was collected for analysis of antibody responses. Swabs of labial, vulvar, perineal, perianal, endocervical, and ectocervical tissue were obtained and used for HPV DNA testing, and liquid-based cytologic testing (Papanicolaou testing) was performed regularly. Tissue obtained by means of biopsy or as part of definitive therapy (including a loop electrosurgical excision procedure and conization) was tested for HPV. RESULTS: The rate of high-grade cervical, vulvar, or vaginal disease irrespective of HPV type (i.e., disease caused by HPV types included in the 9vHPV vaccine and those not included) in the modified intention-to-treat population (which included participants with and those without prevalent infection or disease) was 14.0 per 1000 person-years in both vaccine groups. The rate of high-grade cervical, vulvar, or vaginal disease related to HPV-31, 33, 45, 52, and 58 in a prespecified per-protocol efficacy population (susceptible population) was 0.1 per 1000 person-years in the 9vHPV group and 1.6 per 1000 person-years in the qHPV group (efficacy of the 9vHPV vaccine, 96.7%; 95% confidence interval, 80.9 to 99.8). Antibody responses to HPV-6, 11, 16, and 18 were noninferior to those generated by the qHPV vaccine. Adverse events related to injection site were more common in the 9vHPV group than in the qHPV group. CONCLUSIONS: The 9vHPV vaccine prevented infection and disease related to HPV-31, 33, 45, 52, and 58 in a susceptible population and generated an antibody response to HPV-6, 11, 16, and 18 that was noninferior to that generated by the qHPV vaccine. The 9vHPV vaccine did not prevent infection and disease related to HPV types beyond the nine types covered by the vaccine. (Funded by Merck; ClinicalTrials.gov number, NCT00543543).

No. 279-Female Sexual Health Consensus Clinical Guidelines.

OBJECTIVE: To establish national guidelines for the assessment of women's sexual health concerns and the provision of sexual health care for women. EVIDENCE: Published literature was retrieved through searches of PubMed, CINAHL, and the Cochrane Library from May to October 2010, using appropriate controlled vocabulary (e.g., sexuality, "sexual dysfunction," "physiological," dyspareunia) and key words (e.g., sexual dysfunction, sex therapy, anorgasmia). Results were restricted, where possible, to systematic reviews, randomized control trials/controlled clinical trials, and observational studies. There were no language restrictions. Searches were updated on a regular basis and incorporated in the guideline to December 2010. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. Each article was screened for relevance and the full text acquired if determined to be relevant. The evidence obtained was reviewed and evaluated by the members of the Expert Workgroup established by The Society of Obstetricians and Gynaecologists of Canada. VALUES: The quality of evidence was evaluated and recommendations made using the use of criteria described by the Canadian Task Force on Preventive Health Care (Table).

Treatment of Secondary Vestibulodynia with Conjugated Estrogen Cream: A Pilot, Double-Blind, Randomized Placebo-Controlled Trial.

OBJECTIVE: To assess the efficacy of conjugated equine estrogen cream in reducing dyspareunia associated with secondary provoked vestibulodynia. METHODS: We conducted a randomized, double-blind, placebo-controlled trial that included women with secondary provoked vestibulodynia. Participants were randomly allocated to daily application of conjugated equine estrogen cream on the vulvar vestibule (estrogen group) or daily application of a similar placebo cream (placebo group). All patients were evaluated before and after eight weeks of treatment, using a visual analogue scale for superficial dyspareunia (primary outcome), the McGill Pain Questionnaire for superficial dyspareunia, the Female Sexual Function Index for sexual satisfaction, and vulvoscopy for vestibular erythema. RESULTS: The targeted recruitment for this study was 44 women, but because of funding shortfalls recruitment was limited to 20 women. These 20 participants were randomly assigned to two groups of 10. Improvement of superficial dyspareunia on the visual analogue scale was not significantly different between the two groups (estrogen group: 27% improvement vs. placebo group: 3% improvement, P = 0.29). However, the use of conjugated equine estrogen cream was associated with a significant post-treatment improvement in superficial dyspareunia and in all three secondary outcomes (P < 0.05), whereas this was not the case with the use of placebo. CONCLUSION: Daily application of conjugated equine estrogen cream to the vulvar vestibule could potentially reduce superficial dyspareunia in women with secondary provoked vestibulodynia, but a randomized trial with adequate statistical power will be required to demonstrate this.

No. 279-Female Sexual Health Consensus Clinical Guidelines.

OBJECTIVE: To establish national guidelines for the assessment of women's sexual health concerns and the provision of sexual health care for women. EVIDENCE: Published literature was retrieved through searches of PubMed, CINAHL, and the Cochrane Library from May to October 2010, using appropriate controlled vocabulary (e .g., sexuality, "sexual dysfunction," "physiological," dyspareunia) and key words (e .g ., sexual dysfunction, sex therapy, anorgasmia). Results were restricted, where possible, to systematic reviews, randomized control trials/controlled clinical trials, and observational studies. There were no language restrictions. Searches were updated on a regular basis and incorporated in the guideline to December 2010. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. Each article was screened for relevance and the full text acquired if determined to be relevant. The evidence obtained was reviewed and evaluated by the members of the Expert Workgroup established by The Society of Obstetricians and Gynaecologists of Canada. VALUES: The quality of evidence was evaluated and recommendations made using the use of criteria described by the Canadian Task Force on Preventive Health Care (Table).

2016 IANS International Guidelines for Practice Standards in the Detection of Anal Cancer Precursors.

OBJECTIVES: To define minimum standards for provision of services and clinical practice in the investigation of anal cancer precursors. METHODS: After initial face to face meetings of experts at the International Papillomavirus meeting in Lisbon, September 17 to 21, 2015, a first version was drafted and sent to key stakeholders. A complete draft was reviewed by the Board of the International Anal Neoplasia Society (IANS) and uploaded to the IANS Web site for all members to provide comments. The final draft was ratified by the IANS Board on June 22, 2016. RESULTS: The essential components of a satisfactory high-resolution anoscopy (HRA) were defined. Minimum standards of service provision, basic competencies for clinicians, and standardized descriptors were established. Quality assurance metrics proposed for practitioners included a minimum of 50 HRAs per year and identifying 20 cases or more of anal high-grade squamous intraepithelial lesions (HSILs). Technically unsatisfactory anal cytological samples at first attempt in high-risk populations should occur in less than 5% of cases. Where cytological HSIL has been found, histological HSIL should be identified in ≥ 90% of cases. Duration of HRA should be less than 15 minutes in greater than 90% of cases. Problematic pain or bleeding should be systematically collected and reported by 10% or lesser of patients. CONCLUSIONS: These guidelines propose initial minimum competencies for the clinical practice of HRA, against which professionals can judge themselves and providers can evaluate the effectiveness of training. Once standards have been agreed upon and validated, it may be possible to develop certification methods for individual practitioners and accreditation of sites.