Recommended measurement instruments for menopausal vasomotor symptoms: the COMMA (Core Outcomes in Menopause) consortium.

OBJECTIVE: The aim of the study is to identify suitable definitions and patient-reported outcome measures (PROMs) to assess each of the six core outcomes previously identified through the COMMA (Core Outcomes in Menopause) global consensus process relating to vasomotor symptoms: frequency, severity, distress/bother/interference, impact on sleep, satisfaction with treatment, and side effects. METHODS: A systematic review was conducted to identify relevant definitions for the outcome of side-effects and PROMs with acceptable measurement properties for the remaining five core outcomes. The consensus process, involving 36 participants from 16 countries, was conducted to review definitions and PROMs and make final recommendations for the measurement of each core outcome. RESULTS: A total of 21,207 publications were screened from which 119 reporting on 40 PROMs were identified. Of these 40 PROMs, 36 either did not adequately map onto the core outcomes or lacked sufficient measurement properties. Therefore, only four PROMs corresponding to two of the six core outcomes were considered for recommendation. We recommend the Hot Flash Related Daily Interference Scale to measure the domain of distress, bother, or interference of vasomotor symptoms and to capture impact on sleep (one item in the Hot Flash Related Daily Interference Scale captures interference with sleep). Six definitions of "side effects" were identified and considered. We recommend that all trials report adverse events, which is a requirement of Good Clinical Practice. CONCLUSIONS: We identified suitable definitions and PROMs for only three of the six core outcomes. No suitable PROMs were found for the remaining three outcomes (frequency and severity of vasomotor symptoms and satisfaction with treatment). Future studies should develop and validate PROMs for these outcomes.

Oestrogen-based therapies for menopausal symptoms.

PURPOSE: To summarise the dosing options, regimens, pharmacokinetics, risks and benefits of oestrogen-based therapies for the treatment of menopausal symptoms. METHODS: A review of the literature was undertaken using multiple databases. Randomised trials, observational studies, meta-analyses and review papers were included. RESULTS: Multiple systemic preparations of oestrogen exist and all appear comparable in terms of efficacy. They differ by pharmacokinetics and those preparations that avoid hepatic metabolism have a lower risk profile in general although their use can be limited by skin barriers or patient acceptability. All vaginal oestrogen treatments are comparable in efficacy and have not been associated with any health risks. Side-effects between all preparations differ. CONCLUSIONS: With regards to oestrogen treatments there is not a one size fits all. Multiple treatments are available and a clinician's role is to guide and help women make evidence based, unbiased and informed choices.

Exploring the potential for a set of UK hormone replacement therapy eligibility guidelines: A suggested proposal on the topic of venous thromboembolism.

OBJECTIVE: To explore the feasibility for a set of hormone replacement therapy (HRT) eligibility guidelines that follow a similar structure and appearance to the UKMEC guidance for contraception. To enable non-specialists to feel confident in safely prescribing HRT and to aid selection of the most appropriate first line treatment. METHODS: A literature review was undertaken with evidence summarised on the topic of venous thromboembolism (VTE) which is an area frequently considered a barrier to prescribing. Medical eligibility tables which separated HRT by type were then produced for a set of VTE-related topics. RESULTS: The literature search confirmed the importance of distinguishing between different types and routes of administration when considering the suitability of HRT. Much of the evidence has been based on older synthetic types of HRT and whilst they still have a role in management, these medications carry different risks to the now more accepted use of body identical types. The search also highlighted the nuances involved, increasing the complexity of forming guidelines, with the need for consideration to be given to an individual's own perception of risks and benefits. CONCLUSION: The demand for HRT has risen in recent years and there is a need for this to be managed effectively, particularly for patients in primary care. The production of this type of guidance will enable the non-specialist to feel confident in safe and evidence-based prescribing. The guidelines are also designed to demonstrate to prescribers which complex patients should be referred onto menopause specialists.

Consensus-led recommendations supporting choice and personalisation of Hormone replacement therapy in menopause care.

OBJECTIVE: Inequity of access and choice to different hormone replacement therapy (HRT) products across the UK has been suggested (Hillman, 2020). While, the cause is not entirely understood, potential contributors include conflicting national guidance, economic deprivation and a local formulary approach. With a diverse and growing population of women reaching and living well beyond the menopause, the impact of this inequity is becoming more pronounced, and challenges the goal of providing personalised care. The study objective is to establish a consensus that supports a greater equity of access and choice of HRT and provision of individualised care. STUDY DESIGN: Modified Delphi study designed by UK HCPs with expertise in menopause care. This group identified 40 consensus statements over four key topics, related to access and choice of different HRT products. An online 4-point Likert scale questionnaire, sent to UK HCPs, was used to assess agreement, with a consensus threshold set at 75%. MAIN OUTCOME MEASURES: 150 HCP responses between June and September 2021. RESULTS: A total of 137 responses were received. Analysis identified 37/40 statements attaining very high agreement (≥ 90%) and 3/40 statements attaining high agreement (< 90% and ≥75%). Nine recommendations were developed with the intent to inform potential improvements to menopause care in the UK. CONCLUSIONS: The high levels of agreement displayed suggest a desire to change the way menopause care is delivered in the UK. Implementation of the suggested recommendations has the potential to improve equity of access to licensed treatment options, compliant with the NICE recommendation for personalisation of care.

A core outcome set for genitourinary symptoms associated with menopause: the COMMA (Core Outcomes in Menopause) global initiative.

OBJECTIVE: Genitourinary symptoms, such as vaginal dryness and pain with sex, are commonly experienced by postmenopausal women. Comparing treatments for these genitourinary symptoms are restricted by the use of different outcome measures in clinical trials and the omission of outcomes, which may be relevant to women. The aim of this project was to develop a Core Outcome Set (COS) to be reported in clinical trials of treatments for genitourinary symptoms associated with menopause. METHODS: We performed a systematic review of randomized controlled trials of treatments for genitourinary symptoms associated with menopause and extracted their outcomes. This list was refined and entered into a two-round modified Delphi survey, which was open to clinicians, researchers, and postmenopausal women from November 2019 to March 2020. Outcomes were scored on a nine-point scale from "not important" to "critically important." The final COS was determined following two international consensus meetings. RESULTS: A total of 26 unique outcomes were included in the Delphi process, which was completed by 227 participants of whom 58% were postmenopausal women, 34% clinicians, and 8% researchers. Predefined thresholds were applied to the Delphi scores to categorize outcomes by importance, which informed the e consensus meetings, attended by 43 participants from 21 countries. The final COS includes eight outcomes: (1) pain with sex, (2) vulvovaginal dryness, (3) vulvovaginal discomfort or irritation, (4) discomfort or pain when urinating, (5) change in most bothersome symptom, (6) distress, bother or interference of genitourinary symptoms, (7) satisfaction with treatment, (8) side effects of treatment. CONCLUSION: These eight core outcomes reflect the joint priorities of postmenopausal women, clinicians, and researchers internationally. Standardized collection and reporting of these outcomes in clinical trials will facilitate the comparison of different treatments for genitourinary symptoms, advance clinical practice, and ultimately improve outcomes for symptomatic women.

Video Summary:http://links.lww.com/MENO/A765 .

A core outcome set for vasomotor symptoms associated with menopause: the COMMA (Core Outcomes in Menopause) global initiative.

OBJECTIVE: Vasomotor symptoms (VMS) (hot flashes and night sweats) affect most women over the menopause transition. Comparing the safety and effectiveness of treatments for vasomotor symptoms is limited by the use of inconsistent outcome measures, and uncertainty as to which outcomes are most important to symptomatic women. To address this, we have developed a Core Outcome Set (COS) for use in clinical trials of treatments for VMS. METHODS: We systematically reviewed the primary outcomes measured in randomized controlled trials of treatments for VMS. These were refined and entered into a two-round modified Delphi survey completed by clinicians, researchers, and postmenopausal women between November 2019 and March 2020. Outcomes were scored on a nine-point scale from "not important" to "critically important." Two international consensus meetings were held to finalize the COS. RESULTS: Based on the systematic review, 13 separate outcomes were included in the Delphi process. This was completed by 227 participants of whom 58% were postmenopausal women, 34% clinicians, and 8% researchers. Predefined thresholds were applied to categorize importance scores obtained during Round 2 of the Delphi survey. These informed discussions at the consensus meetings which were attended by 56 participants from 28 countries. The final COS includes six outcomes: 1) frequency of VMS, 2) severity of VMS, 3) distress, bother or interference caused by VMS, 4) impact on sleep, 5) satisfaction with treatment, and 6) side-effects of treatment. CONCLUSION: Implementation of this COS will: better enable research studies to accurately reflect the joint priorities of postmenopausal women, clinicians and researchers, standardize outcome reporting, and facilitate combining and comparing results from different studies, and ultimately improve outcomes for women with bothersome VMS.

Video Summary:http://links.lww.com/MENO/A763 .

Lasers in gynaecology.

The use of lasers to treat gynaecological and urogynaecological conditions including genitourinary syndrome of the menopause, stress urinary incontinence, vaginal prolapse and other conditions, has become increasingly popular over recent years. Following widespread concerns over the use of mesh for treating stress urinary incontinence and pelvic organ prolapse and potential adverse outcomes from the use of mesh, there has been heightened awareness and debate over the introduction and adoption of new technologies and interventions within the speciality. On July 30th 2018 the United States Food and Drug Administration (FDA) issued a warning against the use of energy based devices (EBDS) including laser to perform "vaginal rejuvenation" or vaginal cosmetic procedures. Numerous review articles and editorials have urged for greater evidence on the efficacy and safety of vaginal lasers This review outlines the evidence to date for the use of lasers in the treatment of gynaecological conditions.

National BSUG audit of stress urinary incontinence surgery in England.

INTRODUCTION AND HYPOTHESIS: The aim of the British Society of Urogynaecology (BSUG) 2013 audit for stress urinary incontinence (SUI) surgery was to conduct a national clinical audit looking at the intra- and postoperative complications and provide outcomes for these procedures. This audit was supported by the Healthcare Quality Improvement Partnership (HQIP) and National Health Service (NHS) England. METHODS: Data were collected for all continence procedures performed in 2013 through the BSUG database. All clinicians in England performing SUI surgery were invited to submit data to a central database. Outcomes data for the different continence procedures were collected and included intraoperative and postoperative complications and the change in continence scores at postoperative follow-up Changing trends in stress incontinence surgery were also assessed. RESULTS: We recorded 4993 urinary incontinence procedures from 177 consultants at 110 centres in England: 94.6% were midurethral slings; 86.7% (4331) were submitted by BSUG members with the remaining 13.3% submitted by non-BSUG members. Postoperative follow-up data were available for 3983 (80%) patients: 92.3% (3676) were very much better/much better postoperatively, and 4806 (96.3%) proceeded with no reported complications. There were 187 cases (3.7%) in which a perioperative complication was recorded. Pain persisting >30 days was reported in 1.9% of all patients. CONCLUSIONS: Surgery for SUI has good outcomes in the short term. Midurethral synthetic slings have been shown to be safe and effective as a treatment option, with >90% being very much/much better at their postoperative follow-up.

Mesh removal after vaginal surgery: what happens in the UK?

INTRODUCTION AND HYPOTHESIS: There is little objective evidence regarding complication rates for mesh procedures outside clinical trials. Current coding poorly collects complications of prolapse and continence surgery using mesh. This survey was designed to identify surgeons performing mesh removal and reporting patterns in the UK. METHODS: An electronic questionnaire was sent to all members of the Royal College of Obstetricians and Gynaecologists and members of the Section of Female Neurological and Urodynamic Urology of the British Association of Urologists in the UK. The questionnaire aimed to identify the number of procedures performed for mesh complications and whether they were reported to the Medicines and Healthcare products Regulatory Agency (MHRA) and the patterns of referral and treatment RESULTS: Referral to a colleague in the same hospital was common practice (69 %). Only 27 % of respondents stated that they reported all removals to the MHRA. The numbers of surgical procedures were low, with most respondents performing between one and three procedures each year and many not performing any surgery for a specific mesh complication in the previous year. CONCLUSIONS: Removal of exposed, eroded and/or painful vaginally inserted mesh is performed by many different surgeons in a variety of hospital settings in the UK.

Depression and the incidence of urinary incontinence symptoms among young women: Results from a prospective cohort study.

OBJECTIVE: To examine the association of depressive symptoms with subsequent urinary incontinence (UI) symptoms among young women. SUBJECTS AND METHODS: Data were from a cohort of 5391 young women (born 1973-1978) from the Australian Longitudinal Study on Women's Health. Generalised Estimating Equations (GEEs) were used to link depressive symptoms, and history of doctor diagnosed depression at Survey 2 (S2) in 2000 with the incidence of UI symptoms in subsequent surveys (from S3 in 2003 to S6 in 2012). RESULTS: 24% of women reported the incidence of UI over the nine-year study period, while the prevalence rose over time from 6.8% (at S2, aged 22-27 years) to 16.5% (at S6, aged 34-39). From univariable GEE analysis, women with depressive symptoms or a history of depression were more likely to report subsequent UI symptoms. This remained after adjusting for socio-demographic, body mass index, health behaviours and reproductive factors, with depressive symptoms associated with 37% higher odds (odds ratio 1.37, 95% CI 1.16 to 1.61) and history of depression with 42% higher odds (1.42, 1.17 to 1.74) of incidence of UI. CONCLUSIONS: When woman seek treatment for UI symptoms, health professionals should consider her current or history of depression.

Prevention and treatment of osteoporosis in women.

Osteoporosis affects one in three women. There has been some confusion among women and health professionals about the management of osteoporosis since the publication of the Women's Health Initiative and Million Women studies. This guidance regarding estrogen-based and non-estrogen-based treatments for osteoporosis responds to the controversies about the benefits and risks of individual agents. Treatment choice should be based on up-to-date evidence and targeted to individual women's needs.

A multicentre randomised trial to compare uterine safety of raloxifene with a continuous combined hormone replacement therapy containing oestradiol and norethisterone acetate.

OBJECTIVE: To compare the uterine effects of 60 mg of raloxifene with a continuous combined hormone replacement therapy, a preparation of 2 mg 17beta-oestradiol (E(2)) and 1 mg norethisterone acetate for a duration of 12 months. DESIGN: A randomised, double-blind trial. SETTING: Multicentre: Europe, Israel, South Africa. POPULATION: Asymptomatic postmenopausal women with risk factors for osteoporosis or cardiovascular disease who had an endometrial thickness of less than 5 mm. One thousand and eight women were randomised for the six month core; of these 420 were invited to continue into a six month extension period. METHODS: Randomisation to either raloxifene or continuous combined hormone replacement therapy. Patients, recruiters and assessors were blinded to the treatment used. MAIN OUTCOME MEASURES: The frequency of vaginal spotting/bleeding as recorded in a diary, endometrial thickness and uterine volume as measured by transvaginal ultrasonography at baseline and after 6 and 12 months. RESULTS: After six months of therapy with raloxifene, the rate of women on raloxifene reporting vaginal bleeding and spotting (6.8%) was similar to the rate in the lead-in phase (8.3%) but increased from 7.0% to 55.1% in the continuous combined hormone replacement therapy group. Raloxifene treatment was not associated with a significant change from baseline to endpoint in mean endometrial thickness (P = 0.11), whereas continuous combined hormone replacement therapy treatment was associated with an increase in this value of mean (SD) of 1.2 (2.2) mm (P < 0.001). Compared with raloxifene, mean endometrial thickness for women on continuous combined hormone replacement therapy was significantly increased at endpoint [4.6 (2.1) mm vs 3.5 (1.7) mm; change from baseline P < 0.001]. In the raloxifene group, there was a trend towards a decrease from baseline in uterine volume [from 31.4 (20.3) to 30.3 (16.2) mm; P = 0.37]; in the continuous combined hormone replacement therapy group, there was a significant increase in uterine volume [from 31.3 (16.3) to 54.0 (36.1) mm; P < 0.001], and the difference in the effect of both compounds on change in uterine volume at endpoint reached statistical significance (P < 0.001). Statistically significant differences between the treatment groups were sustained for all parameters during the extension period. Early discontinuation rates, both overall and due to adverse events, were significantly lower (P < 0.001) in the raloxifene group after 6 and 12 months. CONCLUSION: Compared with continuous combined hormone replacement therapy, 6 and 12 months of raloxifene treatment do not lead to vaginal bleeding/spotting, are not associated with increased endometrial thickness or uterine volume and result in a significantly lower rate of early treatment discontinuations in asymptomatic women receiving treatment to prevent long term postmenopausal health risks.