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Abstract
Objective and rationale To identify and appraise current national and international clinical menopause guidance documents, and to extract and compare the recommendations of the most robust examples.
Design Systematic review.
Data sources Ovid MEDLINE, EMBASE, PsycINFO and Web of Science
Eligibility criteria for selecting studies Practice guidance documents for menopause published from 2015 until 20 July 2023. Quality was assessed by the Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument.
Results Twenty-six guidance papers were identified. Of these, five clinical practice guidelines (CPGs) and one non-hormonal therapy position statement met AGREE II criteria of being at least of moderate quality. The five CPGs listed symptoms associated with the perimenopause and menopause to be vasomotor symptoms (VMS), disturbed sleep, musculoskeletal pain, decreased sexual function or desire, and mood disturbance (low mood, mood changes or depressive symptoms). Acknowledged potential long-term menopause consequences were urogenital atrophy, and increased risks of cardiovascular disease and osteoporosis. VMS and menopause-associated mood disturbance were the only consistent indications for systemic menopausal hormone therapy (MHT). Some CPGs supported MHT to prevent or treat osteoporosis, but specific guidance was lacking. None recommended MHT for cognitive symptoms or prevention of other chronic disease. Perimenopause-specific recommendations were scant. A neurokinin 3B antagonist, selective serotonin/norepinephrine (noradrenaline) reuptake inhibitors and gabapentin were recommended non-hormonal medications for VMS, and cognitive behavioural therapy and hypnosis were consistently considered as being of potential benefit.
Discussion The highest quality CPGs consistently recommended MHT for VMS and menopause-associated mood disturbance, whereas clinical depression or cognitive symptoms, and cardiometabolic disease and dementia prevention were not treatment indications. Further research is needed to inform clinical recommendations for symptomatic perimenopausal women.
- Reproductive Medicine
- menopause
- Health Policy
Data availability statement
All data relevant to the study are included in the article or uploaded as supplementary information.
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WHAT IS ALREADY KNOWN ON THIS TOPIC
Clinicians look to best practice guidelines, and position and consensus statements, to inform their practice. To our knowledge, a formal appraisal of the quality, completeness and consistency of guidance papers pertaining to menopause has not been undertaken.
WHAT THIS STUDY ADDS
This review provides a comprehensive overview of areas of consensus between guidance documents, particularly pertaining to menopause assessment and management. It reaffirms that the primary indications for menopausal hormone therapy are vasomotor symptoms, genitourinary symptoms, mood disturbance, and prevention of bone loss, but not clinical depression or cognitive symptoms.
HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY
Areas of consensus regarding menopause management highlighted by this systematic review should provide reassurance for both clinicians and women regarding the availability of evidence-based therapeutic options, and when these can be safely used. Further research and guidance are needed for a number of non-hormonal therapies and management of the perimenopause.
Introduction
The hormonal changes that occur at menopause may result in troublesome symptoms, classically vasomotor symptoms (VMS; hot flushes and night sweats) and genitourinary symptoms (which comprise vulvovaginal and urogenital atrophy symptoms; VVA/UGA), with associated symptoms including sleep disturbance, mood changes and diminished sexual desire.1 Menopausal hormone therapy (MHT) is widely considered to be the most effective treatment to alleviate menopausal symptoms in women without contraindications.2 However, in a recent survey, additional symptoms attributed to menopause by over two-thirds of women included brain fog and fatigue.3
Initially following the publication of the Women’s Health Initiative (WHI) study findings, the use of MHT declined, through personal choice and clinician hesitancy to prescribe,4 5 while the use of unproven complementary and alternative medicines (CAMs) for menopausal symptoms increased.6 7 However, there has been a recent resurgence in MHT use, evidenced, for example, by a 30.5% increase in the number of patients prescribed MHT in the UK between 2021 and 2022.8 This has been substantially attributed to the promotion of MHT by documentaries and social media posts by social influencers.9 10 The clinical care of women at midlife has been described as fragmented, which is partly underpinned by inadequate training of medical students and residents in menopause.2 11 With the surge of interest in menopause, combined with mixed messaging as to the benefits and risks of MHT, there is confusion about menopause and its management among women and healthcare providers alike.12
Guidance documents, published as clinical practice guidelines (CPGs), position statements and consensus statements, are important resources for clinicians providing clinical care.13 However, their quality varies depending on the methodology used in their development, the information available for inclusion and what is selected for inclusion.14 15 Furthermore, CPGs are not designed for point of care use, but are most effectively implemented when used to inform care pathways.16 We previously incorporated guidelines in the development of a Practitioner Toolkit for the Management of Menopause, a simple assessment and decision-making tool for use during consultations, which required updating.17 Our first step was to identify and appraise the guidelines pertaining to menopause published since the Toolkit’s development. To our knowledge, a literature search and systematic review of the methodological quality of the published guidance documents, and the extent of agreement and disagreement in their recommendations, has not been formally undertaken.
The aim of this systematic review, therefore, was to identify and appraise national and international guidance documents for menopause management, published after 2014, to extract and compare the recommendations of those of highest quality. Through this process we ascertained consensus, uncertainty and disagreement in menopause care to inform development of clinical care algorithms and identify where further research is warranted.
Methods
Search strategy and eligibility criteria
This review was conducted and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.18 No amendment was made to the review protocol once initiated. The databases were searched using Ovid MEDLINE, EMBASE and PsycINFO. We also searched Web of Science. Websites of the following professional organisations were manually searched to identify any additional publications: National Institute for Health and Care Excellence (NICE), International Menopause Society (IMS), North American Menopause Society (NAMS), US Endocrine Society (ENDO), British Menopause Society (BMS), European Menopause and Andropause Society (EMAS), Malaysian Menopause Society, and Australian Menopause Society (AMS). The EMBASE full search strategy is provided in online supplemental table 1. The final search results were limited to menopause practice recommendations published in the English language from 1 January 2015 onwards. The initial search was conducted on 22 November 2022 and updated on 20 July 2023. We limited our search to publications from 2015 onwards as the IMS endorsed Practitioner’s Toolkit for Managing the Menopause17 was published in 2014 and we wanted to review the recommendations of guidance documents since then. We searched for documents, collectively described as guidances, published as a practice guideline, recommendation, position, consensus or best practice statement pertaining to menopause for general or urogenital symptoms of menopause.
Supplemental material
Exclusion criteria
We excluded reviews, conference abstracts and individual opinion pieces. Publications exclusively pertaining to premature ovarian insufficiency, early menopause, specific medical conditions and menopause, or long-term complications of menopause were excluded. For documents published after 2015 and then updated, only the most recent version was included. If a short version of a guidance was replaced by the full version, the latter was included.
Study selection
After removal of duplicates, titles and abstracts of the publications were screened for inclusion. Full-text articles meeting the inclusion criteria were then appraised by two independent reviewers (SRD and CH). Disagreement as to the inclusion or exclusion of any article was resolved by consensus discussion (CH, SRD, ST). Two reviewers (CH and ST) independently extracted general characteristics of each publication: title, year, organisation, type of guidance, focus, search methods, and approach to assessing the quality of evidence.
Study evaluation
Four reviewers (CH, EF, RMI, ST) independently evaluated the quality of included guidances using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument.19 The AGREE II is a validated tool for the assessment of the quality of guidelines and includes judgements about methodological rigour and transparency of the development process. The tool consists of 23 items divided into six domains: 1. Scope and purpose (items 1–3); 2. Stakeholder involvement (items 4–6); 3. Rigour of development (items 7–14); 4. Clarity of presentation (items 15–17); 5. Applicability (items 18–21); and 6. Editorial independence (items 22–23). These domains focus on the aim of the guideline, specific health questions, target population, involvement of appropriate stakeholders, representation of the views of the intended users, process used to gather and synthesise evidence, methods to formulate the recommendations, clarity of presentation of recommendations, and formulation of recommendations without bias due to competing interests. Applicability includes tools for implementation, facilitators and barriers, costs, and evaluation of implementation. Each item is rated on a seven-point Likert scale, a score of one indicating ‘strongly disagree’ with no information relevant to a particular item, and seven indicating ‘strongly agree’ with full assessment criteria being met. A score between two and six indicates that the full criteria have not been met and reflects the degree of completeness and quality of reporting19 In accordance with the AGREE II tool, all available supplementary materials were reviewed by the appraisers in this process.
Recommendations and statements from the guidances of at least moderate quality according to their AGREE II scores (described in Data analysis) were extracted into summary tables by three reviewers (CH, SRD, ST) and reviewed by the other co-authors. The extracted data for comparison included diagnosis of menopause, symptoms, long-term effects, indications and benefits of systemic MHT and vaginal oestrogen, age of initiation, contraindications and duration of treatment, risks, and non-hormonal therapies.
Data analysis
Summary statistics were calculated for each AGREE II domain using the total sum score of each domain assigned by the four appraisers (obtained score).19 Standardised domain scores were then calculated as the percentage of the sum of the maximum possible score by the formula: standardised score = (obtained score – minimum possible score)/(maximum possible score – minimum possible score) × 100.19 The results of the standardised score for each domain for all guidances were summarised using median and IQR.
The degree of agreement between the reviewers was determined by calculating the intraclass correlation coefficient (ICC) with a 95% CI. An ICC of <0.40 was defined as poor; 0.40–0.59 as fair; 0.60–0.74 as good; and 0.75–1.00 as excellent.20 For ICC scores<0.75, a consensus was achieved by discussion. A guidance was designated as being high quality if five or more domains scored ≥60%, moderate quality if four domains scored ≥60%, low moderate quality if three domains scored ≥60%, and low quality if two or fewer domains scored ≥60%. A cut-off of 60% was used as per the previous publications.21 22 All analyses were conducted using the Statistical Package for Social Sciences (SPSS) version 28.0.
Patient and public involvement
Patients were not involved in this systematic review.
Role of the funding source
The funding body had no role in the study design, conduct, data analysis, interpretation or manuscript preparation and review.
Results
Characteristics of included studies
As shown in the PRISMA flowchart of study selection, the overall search identified 2402 citations (online supplemental figure 1). After removal of 568 duplicates, 1789 publications were excluded on review of their titles and abstracts. Another 22 publications were excluded for not meeting the inclusion criteria (online supplemental table 2). Together with four documents identified from other sources (three via medical society websites and one from the relevant organisation after a summary version was found in the database search), 27 publications were included. Of these, one guidance was published as two short versions23 24 and these were considered together in further analysis. Hence, the total number of included guidances was 26. Twenty pertained to menopause in general and six were limited to urogenital symptoms of menopause.
Supplemental material
Of the 20 general menopause guidance publications, two were from international societies,25 26 six from regional societies23 24 27–31 and 12 from national societies32–43 (table 1). Eleven guidances providing clinical care recommendations were classified as CPGs.23–25 32 33 35 37–42 The remainder were consensus and positions statements.26–31 34 36 43 Two position statements were limited to non-hormonal therapy for menopause.27 30 Three44–46 of the six publications specifically for urogenital symptoms of menopause44–49 were designated as CPGs (online supplemental table 3).
Summary of the characteristics of the guidance publications on general menopause
Quality appraisal of guidances
Using AGREE II, only the NICE32 and Malaysian Menopause Society40 CPGs met the criteria for high quality (online supplemental table 4). The CPGs of the Association of Scientific Medical Societies of Germany (ASMSG) (2020/2021)23 24 and Indian Menopause Society (2020)39 were of moderate quality. For the consensus and position statements, only the North American Menopause Society (NAMS) position statement on non-hormonal therapy (2023)27 was of moderate quality; all other statements were assessed as low moderate or low quality (online supplemental table 5). Similarly, none of the guidances specific to urogenital symptoms of menopause were rated above low moderate quality.
The AGREE II domain of scope and purpose, and clarity of presentation scored highest across all guidances, while applicability was the least well addressed, with only the NICE CPG32 scoring above 60% in this domain. Scores for rigour of development varied; while NICE32 and Malaysia Menopause Society40 scored highly, the Endocrine Society (ENDO) (2015)38 and the ASMSG23 24 CPGs had borderline acceptable rigour of development (AGREE II score of 59%), and no other guidance was considered adequate in this domain. The Indian Menopause Society CPG39 and the NAMS position statement on non-hormonal therapy27 scored 46% in this domain.
We extracted recommendations and statements from the five highest ranked CPGs addressing general menopause management and MHT.23 24 32 38–40 The ENDO CPG, although designated as low moderate, had three domains scoring ≥60% and one just below 60%,38 therefore a decision was made to include it alongside the other four highest ranking CPGs.
Comparison of recommendations/statements
Menopausal symptoms and diagnosis
All CPGs recommended that the diagnosis of menopause should be symptom based, with biochemical testing only indicated for diagnosis of early menopause (menopause before the age of 45 years), premature ovarian insufficiency (ovarian failure before the age of 40 years) or other special situations listed (table 2).23 24 32 38–40 Symptoms and possible associated symptoms identified by all as being related to the perimenopause and menopause included VMS (hot flushes and night sweats), low mood, mood changes or depressive symptoms (hereafter referred to as mood disturbance), disturbed sleep, musculoskeletal pain and decreased sexual function or desire.23 24 32 38–40 One included ‘memory problems’40 and another ‘cognitive changes’39 as symptoms associated with perimenopause and menopause. Vulvovaginal atrophy or urogenital atrophy symptoms (VVA/UGA), increased risks of cardiovascular disease (CVD) and osteoporosis were specified potential long-term effects of menopause,23 24 32 38–40 with dementia mentioned as being influenced by menopause by one CPG.39
Summary of recommendations/statements from clinical practice guidelines assessed as being of at least moderate quality: diagnosis and menopausal hormone therapy indications
Indications and benefits of MHT
VMS was considered an indication for MHT, either as oestrogen-only therapy (ET) for hysterectomised women, or with the addition of a progestogen to protect the endometrium of non-hysterectomised women, by all CPGs.23 24 32 38–40 Menopause-associated mood disturbances were identified as potential indications for MHT by all CPGs, but most recommended against MHT for the treatment of clinical depression.23 24 32 38 39 All the CPGs, except ENDO,38 recommended MHT for the prevention of osteoporosis.23 24 32 39 40 Three also included MHT as a potential treatment for osteoporosis.23 24 39 40 However, the recommendations made by the Indian Menopause Society and the ASMSG were conditional; the former recommended MHT for treatment in early postmenopausal women39 and the latter only in the presence of menopausal symptoms, or intolerance or contraindications to other bone therapies.23 24 None recommended MHT for cognitive symptoms or for prevention of dementia, primary or secondary CVD prevention, or prevention of diabetes mellitus or sarcopenia, although most noted that MHT reduced incident diabetes mellitus.23 24 38–40 MHT was not recommended for reduction of all-cause or disease-specific mortality by all five CPGs.
All the selected CPGs supported low-dose vaginal oestrogen for VVA/UGA symptoms, including potential use by cancer survivors (online supplemental table 6). In addition to recommending tibolone, a synthetic MHT alternative, for menopausal symptoms, a role for tibolone for bone health was noted,38–40 but only the Indian Menopause Society suggested tibolone could be used for this purpose.39 Testosterone was mentioned as a potential therapeutic option for postmenopausal women with low libido.23 24 32 39 Two CPGs suggested testosterone for low libido that persisted with the use of MHT.23 24 32 Most CPGs highlighted the lack of evidence and safety of compounded hormone therapy.32 38–40
Treatment of perimenopausal women, including contraception and management of menstrual cycle irregularity, was limited to two CPGs.39 40 Both suggested low-dose oral contraception as a treatment option, and one recommended cyclical progestogen therapy if MHT was to be used.39
Initiation, contraindications and risks of MHT
The CPGs generally recommended that the initiation of MHT should be before age 6023 24 38–40 or within 10 years of menopause (table 3).38–40 All CPGs stated that patient preference and a benefit and risk assessment should be factored into decision making about starting MHT. None recommended an upper limit to the duration of use, but most stated duration should be individualised and based on benefits and risks.32 38–40 A history of an oestrogen-sensitive cancer was a consistent contraindication to MHT across the CPGs; a history of CVD or a venous thromboembolic (VTE) event were also specifically listed by three CPGs as contraindications.38–40 The NICE32 and the ASMSG23 24 CPGs stated that CVD risk factors, if managed optimally, were not contraindications for MHT.
Summary of recommendations/statements of clinical practice guidelines assessed as being of at least moderate quality: menopausal hormone therapy initiation, contraindications, duration of treatment and risks
There was agreement among the CPGs that ET may reduce the risk of coronary heart disease (CHD)32 38 or CVD overall,23 24 39 40 while combined oestrogen progestogen therapy (EPT) may have no effect23 24 32 38 40 or minimally increase risk.23 24 32 38 39 All the CPGs listed stroke and VTE as potential adverse effects of MHT, while noting that the risks of both stroke and VTE were less likely with transdermal oestrogen.23 24 32 38–40 The risk of breast cancer with ET use was considered negligible or only minimally increased, while a small or possible increase in breast cancer risk was reported for combined oestrogen and progestogen regimes.23 24 32 38–40 Overall, any increase in breast cancer risk with MHT was considered to be associated with longer duration of use and to decline with treatment cessation.23 24 32 38–40 Several CPGs specified that progesterone and dydrogesterone may be associated with lower risk of stroke,38–40 VTE32 38–40 and breast cancer23 24 38 39 than other progestogens. In the CPGs that discussed vaginal oestrogen and risk, vaginal oestrogen was identified as not increasing CVD risk38 39 or breast cancer risk.23 24 38 39 Ovarian cancer risk with MHT was considered small in two CPGs,23 24 39 whereas two others mentioned the evidence to be either inconclusive or insufficient.38 40 All agreed that unopposed ET increases endometrial cancer risk in non-hysterectomised women.23 24 32 38–40
Non-hormonal management of menopausal symptoms
The recommendations regarding non-hormonal therapies from the five highest ranked CPGs,23 24 32 38–40 along with the NAMS 2023 position statement,27 are summarised in table 4.
Summary of recommendations/statements from clinical practice guidelines assessed as being at least moderate quality: non-hormonal therapy
All recommended selective serotonin/norepinephrine reuptake inhibitors for VMS,23 24 27 32 38–40 but most considered them not to be first line.23 24 32 38–40 Two CPGs specified lack of benefit for menopause-related mood change.23 24 32 Paroxetine and fluoxetine were not advised for breast cancer patients taking tamoxifen.27 32 38–40 Other recommended non-hormonal options for VMS by most of the CPGs included gabapentin23 24 27 38–40 and clonidine.23 24 32 38–40 However, NAMS did not recommend clonidine, mainly due to its adverse effects and the presence of other more effective therapies with fewer adverse effects.27 Oxybutynin, and the recently approved neurokinin 3B receptor antagonist, fezolinetant, were recommended by NAMS for treatment of VMS, acknowledging that long-term use of oxybutynin might be associated with cognitive decline in older adults.27
Most CAMS were considered to lack evidence of benefit,23 24 27 32 38–40 although there was some support for phyto-oestrogens/isoflavones as having potential therapeutic effects.23 24 32 39 Black cohosh was not recommended by most guidances; however, NICE32 and ASMSG23 24 considered it to have potential for VMS.
Complementary and alternative therapies were less well addressed. NAMS alone definitively recommended cognitive behavioural therapy and hypnosis for VMS.27 The remaining guidelines variably stated cognitive behavioural therapy could be considered for low mood,32 sleep disturbance39 40 and VMS,23 24 39 40 and hypnosis could be considered for VMS.39 40 Mindfulness,27 38 yoga,27 40 exercise,23 24 27 38–40 acupuncture27 32 38 40 and stellate ganglion blockade,38 40 were generally found to have insufficient evidence of benefit for VMS. NAMS, however, did recommend stellate ganglion blockade with caution due to the procedural risks.27 The Malaysian and Indian CPGs discussed vaginal laser for VVA/UGA, acknowledging it as a potential therapy, but in need of more evidence.39 40
Discussion
Our systematic review revealed that the majority of current menopause-specific CPGs rate poorly when objectively evaluated. However, when considered together, those of at least moderate quality provide consistent recommendations regarding diagnosis, treatment indications of MHT and certain non-hormonal therapies, and treatment duration.
The selected CPGs were unanimous in their recommendations that MHT is effective for VMS and may alleviate menopause-associated mood disturbances, and that vaginal topical oestrogen is effective for urogenital atrophy symptoms. All recognised that MHT prevents bone loss and fracture; however, specific advice as to when to initiate MHT for this purpose was lacking. Recommendations were uniformly against the use of MHT for cognitive complaints or clinical depression, or for the prevention or treatment of chronic diseases, including CVD, diabetes and dementia. For symptomatic women who choose not to take MHT, or with contraindications for its use, the CPGs consistently identified effective evidence-based pharmacological alternatives. CAMs and complementary therapies, other than CBT and hypnosis, were generally not recommended due to either lack of evidence of efficacy, or not discussed.
Although most CPGs proposed initiation of MHT be limited to women aged less than 60 years, this is based on the earliest analyses of the WHI studies of oral oestrogen and progestogen therapy.50 Long-term follow-up of WHI participants has not shown adverse effects on all-cause mortality51 and non-oral oestrogen use, which was identified by the CPGs as being associated with little or no increase in VTE and stroke risk,52 is now widespread. Thus, reconsideration of MHT for women with moderate to severely bothersome VMS outside the widely proposed age limits might be warranted. It is noteworthy that none of the highly rated CPGs specified an age or time limit for MHT duration.
Clinical care guidance documents can influence healthcare delivery and improve patient outcomes.16 Factors considered critical for guideline robustness include a specifically defined scope and purpose, and clarity of presentation, together with development rigour, stakeholder involvement, editorial independence, and applicability.53 These parameters are all captured by the AGREE II tool, which was systematically developed with item generation, selection scaling, field testing and refinement.19 With the use of this tool, our quality appraisal of the 26 included guidances only identified two that met our predetermined criteria for high quality, three were found to be of moderate quality, and 13 were low moderate quality. Across the guidances, the domains with the highest scores were scope and purpose and clarity of presentation. It is noteworthy, even among publications described as CPGs, that the overall domain score for rigour of development was low, as the majority did not describe the methodology used to formulate and construct recommendations. This does not necessarily mean that formal rigour was absent, but if the methodology was not reported, it was not assessable as per the AGREE II criteria. Furthermore, recommendations are reliant on the interpretation of the committee members where evidence is lacking, limited or uncertain. This limitation is not captured by AGREE II. Applicability was the lowest scoring domain in our review, consistent with the findings of other published guideline appraisals.22 54 Most guidance developers did not include the facilitators and barriers to implementation, or the cost effectiveness of their recommendations, which may hinder the translation of recommendations into clinical practice.55 In future, consideration of all the AGREE II domains by guidance developers may improve the credibility of recommendations and facilitate their uptake in clinical settings.
A disconnect between issues of increasing concern in the community and topics included in the CPGs, as well as the recommendations provided, was apparent. For example, there has been increasing media attention on perimenopause and its manifestations.56–58 However, in the selected CPGs, comprehensive recommendations regarding the perimenopause and its management were mostly lacking. The perimenopause is defined as beginning with variation in menstrual cycle length in women with previously regular cycles, and ends 12 months after the final menstrual bleed.59 Symptoms in the early perimenopause reflect fluctuating ovarian function and include erratic menstrual symptoms, such as premenstrual symptoms and bleeding, mixed with an array of intermittent symptoms of oestrogen deficiency.60 Other symptoms reported by perimenopausal women, such as fatigue, headache, brain fog and weight gain, frequently overlap with symptoms of other medical conditions. Thus recognition, diagnosis and management of the perimenopause in non-menstruating women who do not have VMS can be challenging. The frequent diagnostic uncertainty of the perimenopause, together with many MHTs not being studied or regulator-approved for use in the perimenopause, limited the recommendations that could be made. Research is needed to inform comprehensive support for the diagnostic complexity and care of perimenopausal women.
Subjective memory complaints during the perimenopause, often described by women as ‘brain fog’, are common.61–63 Despite the media echoing women’s concerns regarding menopause-associated brain fog,64 memory problems and cognitive changes were only specified symptoms in two of the five selected CPGs.39 40 Notably, none considered cognitive complaints an independent indication for MHT, possibly because the aetiology appears to be multifactorial, with VMS, poor sleep and mood changes all recognised as contributing factors.61 Consistent with this, randomised controlled trials have not shown improvement in cognitive performance in postmenopausal women with a variety of MHT regimens.65–68 Nonetheless, longitudinal studies to document the frequency of cognitive change during the perimenopause, predisposing factors to any observed change, and the impact of MHT or ovulation suppression on cognitive performance during the perimenopause are needed.
Differences in the therapeutic options included or recommended by the CPGs reflect differences in the evidence base at the time individual CPGs were developed, as well as the availability or approval of specific medications in particular countries. This was most evident in non-hormonal therapies. For example, recommendations regarding phyto-oestrogens have changed over time as the evidence has evolved; earlier CPGs noted some evidence of benefit, whereas subsequent CPGs27 40 do not recommend phyto-oestrogens for VMS due to further findings of inconsistent evidence of benefit. With the neurokinin 3B antagonist, fezolinetant, only approved in 2023, recommendation for its use was limited to the 2023 NAMS statement.27 In relation to complementary and alternative therapies, the discrepancy between CPGs can arguably be interpreted as a positive finding, as this demonstrates progressive growth in the evidence base, with guidance recommendations being updated accordingly.
The ability for clinicians to be able to offer evidence-based, effective, non-hormonal options for women is crucial, especially considering the ready availability and use of unproven and potentially unsafe CAMs.6 7 However, the increasing influence of social media platforms and influencers in relation to menopause and the use of CAMs has been identified as an area of concern.69 In a national Australian study, 13% of postmenopausal women and 19% of perimenopausal women used CAMs to manage their VMS.70 Communication of the ineffectiveness of most of these therapies will enable clinicians to better support women who are considering their use to make informed choices.
Strengths of this systematic review include the comprehensive literature search, use of the internationally recognised AGREE II instrument, and appraisal independently by four independent reviewers. Limiting our review to publications in the English language was a potential drawback. Inconsistencies in the information provided and lack of clearly identifiable recommendations in some CPGs restricted the comparison of some recommendations. AGREE ll also has some limitations. The manual provides clear instructions for rating each domain but this does not eliminate appraiser subjectivity. The domains are all considered independent, with no option for weighting, and there is no total score to distinguish between high- and low-quality recommendations. However, to our knowledge, internationally AGREE II is the most widely used tool for guideline appraisal.
Our appraisal and comparison of the highest quality menopause guidances, as assessed using the AGREE II tool, demonstrates areas of consensus regarding use of MHT and certain non-hormonal therapies in women with menopausal symptoms. Contrary to what is often promulgated in social media, recommendations were consistently against the use of MHT for clinical depression and cognitive complaints, as well as against prevention of cardiometabolic disease and dementia. Greater clarity is needed as to when MHT might be prescribed for the sole purpose of prevention of bone loss. Research to inform best practice in the management of the perimenopause remains an unmet need. The evidence continues to evolve for non-hormonal therapies for VMS, as demonstrated by the discrepancies in some recommendations.
Data availability statement
All data relevant to the study are included in the article or uploaded as supplementary information.
Ethics statements
Patient consent for publication
Ethics approval
Not applicable.
References
Supplementary materials
Supplementary Data
This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.
Supplementary Data
This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.
Supplementary Data
This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.
Footnotes
CH and ST are joint first authors.
Contributors SRD: study design; data interpretation; wrote the drafts and guided the development of the manuscript,
; manuscript review and revision review; full responsibility for the work and/or the conduct of the study, had access to the data, and controlled the decision to publish. ST: data acquisition (literature search and data collection); data interpretation; wrote the drafts; manuscript review and revision review. CH: data acquisition (literature search and data collection); data analysis; data interpretation; wrote the drafts; manuscript review and revision review. RMI: study design; data acquisition (literature search); data analysis; data interpretation; manuscript review and revision review. EF: data analysis; data interpretation; manuscript review and revision review.
Funding This research was funded by the Australian National Health and Medical Research Council (NHMRC) (Grant 2015514). SRD holds an NHMRC Leadership Grant (2016627)
Competing interests SRD reports honoraria from Besins Healthcare, Abbott Healthcare, Mayne Pharma, Health Ed, BioSyent, Lawley Pharmaceuticals and Que Oncology. She has served on advisory boards for Mayne Pharma, Astellas Pharmaceuticals, Besins Healthcare, Theramex and Gedeon Richter, and has been an institutional investigator for Que Oncology and Ovoca Bio.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Provenance and peer review Not commissioned; externally peer reviewed.
Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.