The volume and characteristics of research on gastrointestinal symptoms in ‘natural’ peri- and postmenopause: A scoping review

Abstract

Background:

Menopause has been linked to an array of symptoms, often with adverse effects on quality of life, work and relationships. Despite evidence of economic and social impacts, and a growing population of menopausal individuals, there are significant gaps in knowledge regarding menopause. Gastrointestinal (GI) symptoms in peri- and postmenopause are areas of uncertainty that warrant further investigation.

Objectives:

Following JBI guidance, this scoping review aimed to systematically map research on GI symptoms in ‘natural’ peri- and postmenopause, exploring the volume and conduct of research, and variables investigated that could influence symptom experience.

Eligibility criteria:

Studies assessing GI symptoms (constipation, diarrhoea, vomiting, nausea, abdominal pain, heartburn, faecal incontinence and bloating) in ‘natural’ menopause from all publication dates were included. Studies of medical/surgical menopause, with participants on hormone therapies, or not published in English were excluded.

Sources of evidence:

Results of comprehensive searches of databases (MEDLINE, Embase, PsycINFO, CINAHL, AMED, Scopus, Web of Science, CENTRAL, ProQuest Dissertations and Theses), trial registries, citation and web-searches were screened against eligibility criteria.

Charting methods:

Data were charted in a standardised template, including study designs, populations, countries, GI symptoms studied, methods used for their assessment, and variables investigated. Analyses included frequency counts and percentages, with findings presented in visual and tabular formats.

Results:

Overall, 122 studies were included, published between 1981 and 2024. Studies were predominantly quantitative in design, with constipation the most frequently investigated symptom (n = 58), in contrast to vomiting (n = 4). Results highlighted limited studies from South American and African regions, and insufficient reporting of the criteria used to determine menopausal stages and assess GI symptoms.

Conclusions:

While many studies were identified, findings indicate evidence gaps and methodological considerations pertinent to researchers and funders, regarding study designs, assessment and reporting of menopausal stages and GI symptoms, and the variables investigated. Recommendations are made for future research.

Introduction

In the UK, 13 million people are estimated to be peri- or postmenopausal, ¹ with 80%–90% of women thought to be negatively impacted by menopausal symptoms. ² ‘Natural’ menopause is reached when an individual has not had a menstrual cycle in the prior 12 months, due to a decline in ovarian function associated with ageing, rather than from surgical or medical intervention. ³ Menopause commonly occurs between 44 and 54 years of age; ⁴ however, it is proposed to be a ‘process’ rather than a single event. ⁵ The Stages of Reproductive Ageing (STRAW+10) outlines the stages of menopause, with the transition from reproductive life to one year following the final menstrual period (FMP) defined as the ‘perimenopause’. ⁶ The period leading up to the FMP is further categorised into the early and late menopausal transition (MT). Each stage is characterised by variability in menstrual cycle length and regularity, and significant fluctuations in levels of sex hormones including oestrogen, progesterone, luteinising hormone, and follicle-stimulating hormone. ⁷ This ‘reproductive hormonal milieu’ and the gradual decline in sex hormones following the FMP have been associated with an array of symptoms, ⁸ including hot flushes, night sweats, sleep disturbances, joint aches, vaginal dryness, brain fog, depression and anxiety. ⁷ Despite a growing global population of menopausal individuals, ³ and evidence of economic and social impacts associated with persistent menopausal symptoms,^1,8,9 researchers argue that there are significant gaps in our understanding of menopause and the factors that influence the experience of symptoms.^10,11

Gastrointestinal (GI) symptoms in peri- and postmenopause are one such area of uncertainty. GI symptoms as outlined by the National Institutes of Health (NIH) Patient Reported GI Symptom Scale ¹² include diarrhoea, constipation, nausea, vomiting, abdominal pain, bloating, heartburn and faecal incontinence. These symptoms are highly prevalent in the general population, placing a significant burden on health systems.^13,14 Recent news coverage and sources of patient information have suggested an association between menopause and heightened risk of GI symptoms.^15,16 However, GI symptoms are not acknowledged as key menopausal symptoms in international and UK guidelines.^17,18 This may be due to the omission of GI symptoms from menopausal symptom assessment scales commonly used in research,^19–23 or the limited availability of high-quality evidence from human studies to underpin recommendations.

Exploratory searches were conducted using MEDLINE (Ovid), JBI Evidence Synthesis, Open Science Framework (OSF) and Epistemonikos (February 2024) to gauge available evidence on GI symptoms in the peri- and postmenopause. Searches identified primary studies, but few evidence syntheses, with one scoping review exploring swallowing difficulties and symptoms of the oral cavity only, ²⁴ and one systematic review ²⁵ examining the relationship between menopausal stage and irritable bowel syndrome (IBS), a condition with symptoms including abdominal pain and dysfunctional bowel habits. ²⁶ While the systematic review by Adeyemo et al. ²⁵ found limited evidence for an association, searches were restricted to the PubMed database, therefore potentially missing eligible studies, and focused on GI symptoms linked to IBS only. Furthermore, new research has been published since the searches by Adeyemo et al. ²⁵ were completed in 2010. These new studies highlight conflicting findings regarding the relationship between menopausal stage and the frequency or severity of GI symptoms, including those common to IBS. For example, higher rates of constipation ²⁷ and faecal incontinence ²⁸ have been reported in postmenopausal compared with premenopausal individuals, while in contrast, other studies found no significant differences in the prevalence or severity of constipation,^29–31 faecal incontinence, ³² bloating ³³ or abdominal pain ³⁴ across menopausal stages. Indeed, some studies have found that premenopausal women were more likely to be affected by GI symptoms, such as chronic constipation ³⁵ and abdominal pain ³⁰ , than women in later stages. These contradictory findings might be explained by the heterogeneity of definitions and methods used in these studies and indicate the need for an up-to-date review of research in this area.

Evidence suggests there may be ethnic and geographic variability in menopausal symptom prevalence and severity, ³⁶ and that an individual’s experience of menopause can be influenced by many hormonal, psychological and sociocultural factors (see Figure 1). Sex hormones such as oestrogen and progesterone, are thought to play an important role in GI health.^37–39 Fluctuations in these sex hormones associated with the MT could lead to GI symptoms, through altered perceptions of pain, ⁴⁰ changes in gut motility, ⁴¹ intestinal mucosa barrier functions, ⁴² and immune and inflammatory processes. ³⁷ The composition of the gut microbiome may be impacted by hormonal changes, while also contributing to sex hormone metabolism.^43,44 Such changes within the gut could result in the onset of new GI symptoms^45,46 or exacerbations in individuals diagnosed with IBS or inflammatory bowel diseases. ⁴⁷ However, Yang et al. ⁴⁸ suggest there is insufficient evidence to determine whether microbial changes triggered by hormonal fluctuations contribute to the experience of GI symptoms in the menopause.

Figure 1.

Possible correlates and risk factors associated with increased risk of GI symptoms in peri- and postmenopause.

Sources: Nie et al., ³⁷ Coquoz et al., ³⁹ Zia and Heitkemper, ⁴¹ Shieh et al., ⁴² Drossman, ⁴⁶ Thomas et al.,^{49 Meleine and Matricon, 50 Mulak et al., 51 Hogan et al. 52}

GI: gastrointestinal.

Psychological and social variables may also contribute to GI and menopausal symptoms. The timing of the MT may co-occur with multiple stressors, such as additional caretaking responsibilities for elderly parents or children, bereavement, alongside frustrations with work roles and changing personal identities. ⁵³ Such sociocultural factors could contribute to increased susceptibility to psychological distress, ⁴⁹ or negatively impact sleep quality and dietary patterns, which in turn could initiate or intensify existing GI symptoms.^46,48

A lack of funding for women’s health research has resulted in knowledge gaps related to menopause.^10,11,54 Menopause is growing in visibility in the UK media ⁵⁵ and the recent Women’s Health Strategy for England ¹¹ established menopause as a key priority for future research investment. In consequence, this is an opportune time to identify evidence gaps and key areas for further study. With no recent or ongoing evidence syntheses exploring GI symptoms in peri- and postmenopause, and sufficient studies for a scoping review, these are areas of uncertainty that warrant further investigation. In consequence, this scoping review aimed to systematically search for, select and map research on GI symptoms in ‘natural’ peri- and postmenopause to identify gaps in the evidence to inform future research. The review had the following three objectives:

• To gauge the volume of evidence from published and grey literature examining patient-reported GI symptoms (nausea, vomiting, bloating, constipation, diarrhoea, heartburn, abdominal pain and faecal incontinence) in ‘natural’ peri- and postmenopause.

• To consider how research on GI symptoms in ‘natural’ peri- and postmenopause has been conducted (including study designs; measures of GI symptoms; timeframes of symptom recall; menopausal stages studied, and the criteria used to determine stages).

• To identify the key variables that have been measured in research on GI symptoms in ‘natural’ peri- and postmenopause (for e.g. correlates of GI symptoms: sex hormone levels, body mass index, perceived stress, ethnicity).

Methods

A scoping review methodology was selected to address the research objectives as it is deemed appropriate for broad questions with the goal of exploring the volume, type and characteristics of available evidence. ⁵⁶

Methods for this review aligned with JBI guidance for the conduct of scoping reviews^57,58 using systematic and reproducible methods to search for, select and map relevant studies, thus minimizing bias. Review reporting was guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Scoping Review (PRISMA-ScR) extension ⁵⁹ for transparency, with the completed checklist available in Supplemental Appendix 1.

As this is a review of existing literature, ethical approval was not necessary.

Protocol

A protocol was registered on OSF (https://osf.io/4w5xc/). Deviations from methods outlined in this protocol are reported with justifications in Supplemental Appendix 2.

Eligibility criteria

Eligibility criteria were pre-specified, defining the scope of this review, supporting development of search strategies, and facilitating decision-making regarding the relevance of records identified through comprehensive searches. ⁵⁷ The JBI Participant, Concept, Context framework ⁵⁷ was used to categorise eligibility criteria, as outlined in Table 1.

Table 1.

Eligibility criteria for the identification and selection of studies.

Eligibility domain	Inclusion criteria	Exclusion criteria
Population	Studies of individuals described as experiencing: • ‘Natural’ perimenopause or • Menopausal transition or menopause • Postmenopause	Studies of individuals: • Experiencing hysterectomy, surgical, radiotherapy-induced or drug-induced menopause, or undergoing treatment for cancer • With chronic illness that influences menstrual cycles (e.g. polycystic ovary syndrome) • With primary ovarian insufficiency or premature menopause • Taking hormone therapies or hormonal contraceptives • Focusing only on pre-menopausal individuals (<40 years + experiencing regular periods) • With a mix of participants experiencing ‘natural’ and surgical, radiotherapy or drug-induced menopause, or taking hormone therapies, will be excluded if separate data is not provided • Describing older or midlife individuals that do not refer to menopausal status (i.e. the terms perimenopausal, menopausal or postmenopausal are not used)
Concept	Studies focusing on patient-reported GI symptoms 12 including: • Bloating, abdominal pain, constipation, diarrhoea, nausea, vomiting, heartburn, faecal incontinence or describing non-specific GI or digestive symptoms • The above GI symptoms associated with disorders of gut-brain interaction (e.g. irritable bowel syndrome) • The above GI symptoms associated with organic GI disorders with an underlying diagnostic pathology (e.g. inflammatory bowel disorders, ulcerative colitis and Crohn’s disease) • Non-hormonal interventions for treating GI symptoms in perimenopausal or postmenopausal individuals	Studies that focus only: • On menopausal symptoms not related to the GI system (e.g. vasomotor, skin, genitourinary, mood symptoms) • On oral symptoms (dry mouth, swallowing difficulties), or symptoms not covered by the NIH PROMIS GI Scale (e.g. disordered eating) 12 • On non-patient reported measures (e.g. electrophysiological measures, gut motility, visceral pain sensitivity, structural changes to the gut) • On GI symptoms as an adverse effect of: ○ Hormone replacement therapy or interventions for managing non-GI menopausal symptoms (e.g. selected oestrogen receptor modulators) ○ Interventions for other conditions (e.g. bisphosphonates for osteoporosis)
Context	All countries	–
Types of evidence	Ongoing/published primary research studies (including epidemiological, interventional, qualitative or mixed methods approaches) and evidence syntheses (systematic, scoping or rapid reviews) published in journals, dissertations, reports, grey literature, or clinical trial registries	Animal studies, laboratory studies that do not consider patient-reported GI symptoms, editorials and commentary, case studies, case reports, narrative and literature reviews, conference abstracts
Language	English-language publications	Non-English language publications
Publication date	All years	No restriction on publication date

Population

This review focuses on GI symptoms in ‘natural’ menopause, which is characterised by fluctuations in sex hormones during perimenopause, followed by a gradual decline postmenopause. ⁶ Studies focusing on medically induced or surgical menopause were excluded, as these may cause an abrupt fall in oestrogen and progesterone, ³⁶ and could contribute to more severe menopausal symptoms. ⁶⁰ As hormone replacement therapies (HRT) may make it difficult to discern menopausal stage ⁶¹ and could influence the experience of GI symptoms, ⁶² studies recruiting individuals on HRT were excluded. Furthermore, as the menopausal stage of individuals with polycystic ovary syndrome, or those who have undergone hysterectomy, cannot be determined using menstrual cycle criteria, ⁶ studies focusing on these populations were excluded.

Variable nomenclature has been used to classify menopausal stages, ⁶¹ with the term ‘pre-menopausal’ inconsistently applied, sometimes being used to describe both the entire reproductive period, and also the 1–2 years prior to the cessation of menstruation. For clarity, studies of ‘pre-menopausal women’ only (aged <40 years with regular menstrual cycles) were excluded.

Concept

This scoping review focused on GI symptoms based on eight key categories described in the NIH Patient Reported GI Symptom Scale. ¹² To avoid duplication with a recent scoping review, ²⁴ studies on swallowing difficulties and oral symptoms were excluded. Patient-reported GI symptoms were the focus of this review, so studies reporting only laboratory or electrophysiological outcomes (such as GI motility or structural changes to the gut in menopause) were excluded.

Context

Studies from any country or region were included to facilitate identification of all variables (including ethnicity) studied that could impact on the experience of GI symptoms in peri- and postmenopause.

Language

Non-English publications were ineligible for inclusion due to translation costs, and the potential for language bias was noted. ⁶³ Language limits were not applied to searches, but instead, non-English publications were excluded during screening, as recommended by Pieper and Puljak. ⁶⁴

Publication dates

Studies from database inception to the search date were included, as this review aims to determine the volume of available evidence.

Types of evidence

To address objectives regarding the volume and conduct of available research, published and ongoing quantitative and qualitative primary research studies, and evidence syntheses were included. The following evidence sources were excluded: animal studies, laboratory studies (that did not assess patient-reported GI symptoms), editorials, case reports, literature reviews (that did not use systematic methods for the identification and selection of studies), and conference abstracts due to limited details of study methods and measures.

Sources of evidence

As recommended by JBI guidance, ⁵⁷ searches were performed following a three-step process as outlined below:

Initial scoping searches

Text analysis of relevant studies from exploratory searches supported the identification of controlled vocabulary (e.g. Medical Subject Headings (MeSH)) and synonyms for the population (i.e. perimenopause) and the concept (i.e. named GI symptoms). An Information Specialist with expertise in evidence synthesis (NS) developed all search strategies. The Ovid MEDLINE strategy is presented in Box 1, with all other strategies reported in Supplemental Appendix 3.

Box 1.

Search strategy for Ovid MEDLINE.

1 Exp menopause/ 2 (Menopaus* or perimenopaus* or peri-menopaus* or postmenopaus* or post-menopaus* or postreproductive or post-reproductive or climacteric).ti,ab. 3 1 or 2 4 Irritable bowel syndrome/ 5 Exp inflammatory bowel diseases/ 6 Exp “signs and symptoms, digestive”/ 7 ((Digestive or bowel or gut or gastro* or colonic) adj2 (symptom* or habit* or issue* or issue* or problem* or dysfunction* or complaint*)).ti,ab. 8 ((Digestive or gastro*) adj3 symptom*).ti,ab. 9 (GI adj symptom*).ti,ab. 10 IBS.ti,ab. 11 (Inflammatory adj bowel).ti,ab. 12 (Ulcerative adj colitis).ti,ab. 13 Crohn*.ti,ab. 14 (Irritable adj bowel).ti,ab. 15 (Diarrh* or constipat*).ti,ab. 16 ((Loose or watery) adj stool*).ti,ab. 17 ((Bowel* or defecat*) adj2 (frequen* or urgen* or infrequen*)).ti,ab. 18 (Incomplete adj evacuation).ti,ab. 19 (Bloating or bloated or gassiness or gaseousness or flatulence or flatulent or flatus or (abdom* adj disten*) or (swollen adj abdom*) or (swelling adj2 abdom*) or (postprandial adj fullness) or (post-prandial adj fullness)).ti,ab. 20 ((Gurgling or rumbling) adj2 (abdom* or stomach or gastro*)).ti,ab. 21 ((Abdom* or stomach or epigastric or rectal or rectum or belly) adj2 (pain* or cramp* or ache* or colic or discomfort)).ti,ab. 22 (Reflux or GERD or dyspepsia or indigestion or heartburn or regurgitat*).ti,ab. 23 (Belch* or burp* or eructation or hiccup*).ti,ab. 24 (Nausea* or vomit* or emesis or retching).ti,ab. 25 ((Faecal or fecal or anal or bowel) adj2 (incontinen* or leak* or soiling)).ti,ab. 26 ((Bowel* adj control*) or encopresis).ti,ab. 27 ((Gut or digestive or gastro* or bowel* or colon*) adj2 health*).ti. 28 Or/4-27 29 3 and 28 30 Exp animals/ not humans/ 31 29 not 30

Full database searches

The following bibliographic databases were searched on 4 March 2024 without date or publication type restrictions: MEDLINE, Embase, APA PsycINFO (Ovid); CINAHL, AMED (EBSCO); Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials (Wiley); Web of Science Core Collection (Clarivate Analytics); Scopus (Elsevier) and ProQuest Dissertations and Theses Global. Search strategies were tailored for each database using appropriate syntax and controlled vocabulary.

Grey literature and supplementary searches

Searches of professional associations and key websites (e.g. British Menopause Society), Google/Google Scholar and clinical trials registries (ClinicalTrials.gov and the World Health Organization International Clinical Trial Registry Platform) were completed from April to June 2024 to identify grey literature. ⁶⁵ Simplified search strategies were used for Google/Google Scholar, with the first ten pages of each search screened by one reviewer. Full details are provided in Supplemental Appendix 3. Forwards and backwards citation-searching of included studies from database searches was completed using CitationChaser in May 2024, ⁶⁶ and bibliographies of key review articles were checked.

Selection of sources of evidence

All records from searches were imported into EndNote X9.3.3 (Clarivate Analytics) and duplicates removed using manual checks and EndNote functionality.

Pilot screening

Pre-specified eligibility criteria (Table 1) informed the selection of studies. Three reviewers (NS, CP, KT) independently reviewed titles/abstracts of a random sample of 100 records in Rayyan ⁶⁷ to pilot eligibility criteria. Disagreements were discussed, and screening documentation was refined to ensure clarity.

Title/abstract and full-text screening

Screening by two independent reviewers is recommended to reduce the risk of bias or human error; ⁶⁸ however, due to time constraints, one reviewer screened 100% of records (NS), with a second reviewer (KT) screening 50% at both stages of screening. Firstly, titles/abstracts were assessed against eligibility criteria, followed by the full text of selected articles. Articles not available through University Library services were excluded, though citations are listed in Supplemental Appendix 4. Disagreements at both screening stages were resolved through consensus.

Data charting methods

A Microsoft Excel template was developed to chart data items relevant to review objectives. The following data items were charted: citation; study design; populations studied; GI symptom(s) investigated, as well as the methods (e.g. Menopause-Specific Quality of Life (MENQOL) checklist) ⁶⁹ and recall timeframe used in their assessment; definitions of menopausal stage (e.g. STRAW + 10⁶); countries; and variables studied (i.e. predictors, correlates or interventions). Additional items (e.g. new variables) were added to the template as the reviewer became familiar with the included literature. As this review is exploratory and does not aim to synthesise findings, study results were not extracted. This is consistent with guidance for the conduct and appropriate use of scoping review methods. ⁵⁷

The template was piloted by one reviewer (NS) on ten studies covering a range of evidence types. Independent data charting by two reviewers is recommended to minimise bias and human error; ⁵⁸ however, resource limitations required that one reviewer charted all data.

Quality assessment

Quality assessment of included studies is not a mandatory step in scoping reviews ⁷⁰ and was not completed for this review.

Data analysis and synthesis

Descriptive analyses focused on frequency counts of charted data, with percentages calculated using Excel (Microsoft; Version 2402) and presented in tabular, graphical or visual formats aligning with review objectives, as indicated in Table 2.

Table 2.

Analyses by review objective.

Review objective/question	Frequency counts
What is the volume of evidence examining eight key categories of GI symptom in peri- and postmenopause?	Overall number of included studies
	Number of studies by year of publication
	Number of studies by publication type (i.e. journal article, dissertation, report)
	Number of studies by geographic location, with countries categorised into regions using WorldinData definitions 71
	Number of studies by GI symptom (mapped to NIH PROMIS 12 domains: diarrhoea, constipation, nausea, vomiting, bloating, faecal incontinence, heartburn and abdominal pain)
	Number of studies with a primary objective to investigate GI symptoms in ‘natural’ peri- or postmenopause
How has research on GI symptoms in natural peri- and postmenopause been conducted?	Number of studies by design (i.e. case-control, cross-sectional, longitudinal, randomised control trials, qualitative, systematic reviews)
	Number of studies by menopausal stage (i.e. perimenopausal, early menopausal transition, late menopausal transition, postmenopausal individuals)
	Number of studies by criteria used to assess menopausal stage (e.g. STRAW + 106)
	Number of studies by measure used to assess GI symptoms (e.g. validated symptom scales)
	Number of studies by timeframe used for recall of GI symptoms (e.g. previous week; previous 12 months)
What key variables have been measured in research on GI symptoms in natural peri- and postmenopause?	Number of studies by variable (e.g. age, levels of sex hormones, perceived stress, ethnicity) to investigate the relationship between the variable and GI symptom frequency, severity, or prevalence Variables were grouped into demographics; lifestyle factors; clinical markers and comorbidities; biomarkers; menopause-related factors and interventions

Results

Database and supplementary searches retrieved 13,111 and 3529 records, respectively. After duplicates were removed, 9569 records were assessed for eligibility from titles/abstracts. A total of 311 articles were retrieved for full-text screening, with 122 studies identified for inclusion. Figure 2 (PRISMA flow diagram) indicates the process of study selection. Details of excluded studies with reasons are available in Supplemental Appendix 4.

Figure 2.

PRISMA flow diagram: study identification and selection.

Characteristics of included studies

Results are reported in alignment with review objectives, considering:

• The volume of evidence on GI symptoms in ‘natural’ peri- and postmenopause.

• The conduct of research.

• The variables investigated.

Study characteristics for 122 included studies outlining brief citation details, populations, GI symptom(s) assessed, study designs and variables investigated are provided in Supplemental Appendix 5.

Volume of evidence

Figure 3 shows the timeline of included studies, with 34% (n = 42) published within the last 5 years.

Figure 3.

Number of included studies by publication date.

Table 3 provides summary characteristics for included studies relating to the volume of evidence. This shows that most studies (n = 116; 95.1%) were published as journal articles, with one dissertation, ⁷² two preprint publications,^73,74 and three clinical trial registrations^75–77 identified as ‘grey literature’. Studies were conducted in 35 countries represented by six geographic regions, ⁷¹ ranging from only 0.8% (n = 1) in South America, compared with 44.3% (n = 54) carried out in Asia. From 122 included studies, only 18% (n = 22) stated a primary objective that related to the study of GI symptoms in ‘natural’ peri- or postmenopause, while 82% (n = 100) either investigated a GI symptom as one of a range of menopausal symptoms or assessed menopause as one potential risk factor for a GI symptom. Constipation was the most studied GI symptom (n = 58; 47.5%), while only 4 (3.3%) studies investigated vomiting in ‘natural’ peri- or postmenopause.

Table 3.

Summary of study characteristics relating to the volume of available evidence (n = 122 included studies).

Studies by publication type: n/122 (%)			Studies with a primary objective relating to GI symptom(s) in peri- or postmenopause: n/122 (%)
Journal article	116 (95.1)	25,27–35,78–183	Yes	22 (18)	25,31,33,34,82,90–92,97,98,106,110,117–119,125,128,131,139,167,170,180
Dissertation	1 (0.8)	72	No	100 (82)	27–30,32,35,72–81,83–89,93–96,99–105,107–109,111–116,120–124,126,127,129,130,132–138,140–166,168,169,171–179,181–183
Preprint	2 (1.6)	73,74
Clinical trial registration	3 (2.4)	75–77
Studies by geographical region: n/122 (%)			Studies by GI symptom: n/122 (%); (included studies investigating ⩾1 GI symptom)
Asia	54 (44.3)	27,28,33,35,73,76,77,81,84-87,90,96,99,106,108,110,121–131,133,135,136,138,144,146,148,158,159,161,162,164–166,168,169,171–173,177–179,181–183	Constipation	58 (47.5)	25,27,29–33,35,73–75,77–79,83,85,91,92,94,96,98,100–102,104,106,108,109,117–119,121,123,128,131–133,135,136,138,139,143–146,148,149,154,158,161,162,167,170–172,179,180,183
North America	31 (25.4)	29–31,34,72,75,83,93,95,101,107,111,113–120,132,134,139,143,145,149,152,167,170,175,176	Bloating or flatulence	46 (37.7)	25,33,72,74–76,78,79,84–87,89,95,98–102,105,109,111,112,115,117–120,124,126,127,129,130,132,134,137,141,142,158,166,169,173,175,178,181,182
Europe	20 (16.4)	80,88,89,91,92,97,98,105,109,140–142,147,150,151,157,160,163,174,180	Diarrhoea	32 (26.2)	25,27,29,31,33,73–75,77,83,85,92,98,100,101,104,108,115,117–119,131,132,136,139,146,149,162,170–172,180
Oceania	8 (6.6)	78,94,102–104,154–156	Abdominal pain	27 (22.1)	25,29,30,33,34,73,74,78,89,98,100,101,115–119,132,136,141,142,151,160,164,168,176,179
Africa	4 (3.3)	79,82,137,153	Nausea	19 (15.6)	25,29,74,78,93,100,101,107,117–120,127,132,136,137,141,152,177
South America	1 (0.8)	32	Faecal incontinence	19 (15.5)	28,32,81,83,88,90,96,110,122,125,135,138,140,148–150,157,163,165
Multiple regions	3 (2.5)	25,100,112	Heartburn	18 (14.8)	27,29,73,82,85,97,100,101,117–120,132,147,152,153,155,168
Not stated	1 (0.8)	74	Vomiting	4 (3.3)	74,117–119
			Digestive symptoms – unspecified	8 (6.6)	80,103,113,114,150,156,159,174

Conduct of studies

Table 4 presents summary data on the conduct of studies on GI symptoms in ‘natural’ peri- and postmenopause.

Table 4.

Summary of study characteristics relating to the conduct of research.

Studies by design: n/122 (%)			Studies by menopausal stage of recruited participants: n/122 (%)
Systematic review	1 (0.8)	25	Peri	57 (46.7)	30,31,34,72,74,76,77,82,84–86,89,92–94,99–105,107–109,115–120,123,126,130,131,133–136,138,141–144,153–156,164,166,172,174–178,182
Quantitative	118 (96.7)					Randomised controlled trial	5 (4.1)	82,89,106,139,170	Peri only	9 (7.4)	72,76,82,99,133,134,143,144,153
Non-randomised trial	3 (2.4)	97,98,131	Post	107 (87.7)	25,27–35,73–75,77–81,83–89,91,92,94–98,102–107,109–132,135–142,145–152,154–165,167–183
Clinical trial registration	3 (2.4)	75–77	Post only	33 (27)	73,75,87,91,97,98,106,110–112,121,122,124,127–129,137,139,140,146,150,151,158,159,161,162,167–171,173,181,183
Cross-sectional	89 (73)	27–30,32,33,35,72–74,79–81,83–87,90,92,93,95,96,99–102,104,105,107–120,122–130,132–138,141–144,146–148,150–153,158,159,161,164–166,168,169,171–175,177–182	Criteria used for determining menopausal stage: n/122 (%)
Longitudinal	14 (11.5)	31,34,78,88,94,103,121,145,149,154–156,160,167	Not stated	44 (36)	25,28,29,32,33,35,76–78,80–82,88,90,95–97,99,107,108,110,121,122,124,129,132,138–140,145,147–149,152,157,159,161,163,165,166,168,170,171,179
Case-control	3 (2.4)	91,157,183	Age-range	9 (7.4)	83,89,109,126,143,144,153,167,176
Retrospective	1 (0.8)	140
Mixed method	1 (0.8)	162	STRAW/STRAW+10	13 (10.7)	31,34,84,92,100,101,103,105,123,130,133,164,182
Qualitative	2 (1.6)	163,176	Other definition	56 (45.9)	27,30,72–75,79,85–87,91,93,94,98,102,104,106,111–120,125,127,128,131,134–137,141,142,146,150,151,154–156,158,160,162,169,172–175,177,178,180,181,183
Measures used to assess GI symptoms: n/122 (%)			Timeframe reported for recall of GI symptoms: n/122 (%)			Not stated	9 (7.4)	25,76,79,133,138,145,161,162,179
Not stated	84 (68.8)	25,27,28,32,72,73,76–79,81–83,86–89,91–93,96–99,101–103,108–121,123–128,130,131,133,135,137,138,140–147,149–152,157–159,161–164,166,168,169,171,173–176,178–180,182	Validated measure	66 (54.1)	28,33,35,72,73,75,77,81–84,86–89,92,95,103,106,110,112,115–132,134–136,139–143,146–149,151,156–158,160,169,171–175,177,178,181,182
⩽1 week	6 (4.9)	31,34,74,107,139,170
>1 week, ⩽1 month	14 (11.5)	29,33,84,95,104–106,129,132,136,156,167,177,181	Study-specific tool	47 (38.5)	27,29–32,34,74,78,80,85,90,91,93,94,96–102,104,105,107–109,111,113,114,137,144,150,152–155,159,163–168,170,176,180,183
>1 month, ⩽3 months	5 (4.1)	30,75,80,122,148
>3 months–1 year	13 (10.7)	35,85,90,94,100,134,153–155,160,165,172,183

Study designs

Study designs were predominantly quantitative (n = 118; 96.7%), with only two (1.6%) qualitative,^163,176 and one mixed-methods study (0.8%) included. ¹⁶² One systematic review ²⁵ met eligibility criteria, and 73% of included studies were cross-sectional (n = 89), with other studies of longitudinal design (n = 14; 11.5%), randomised controlled trials (n = 5, 4%), non-randomised studies (n = 3; 2.5%), case-control (n = 3; 2.5%), and one retrospective study (0.8%).

Populations

Most included studies recruited individuals described as postmenopausal (n = 107; 87.7%), with 57 studies (46.7%) including those in perimenopause. Further analysis indicated that just over a third of included studies (n = 42; 34.4%) focused on individuals of one menopausal stage only (perimenopausal only: n = 9; postmenopausal: n = 33). Criteria or definitions used to determine menopausal stage were not stated in 36% of studies (n = 44), with age ranges used to identify individuals for inclusion in a further nine studies (n = 7.4%). STRAW/STRAW + 106, ¹⁸⁴ were cited as the criteria used for categorising menopausal stages in 13 studies (10.7%), while 56 (45.9%) provided alternative definitions (e.g. studies cited an adapted version of the WHO classification, ¹⁸⁵ or classified individuals as perimenopausal if they had experienced menstrual bleeding in the prior 12 months, but not in the last 3 months).

Measures of GI symptoms

Studies used a range of measures to assess GI symptoms, with 66 studies (54.1%) citing a validated menopausal or GI symptom screening tool (e.g. MENQOL, ¹⁸⁶ Wexner Incontinence Scale ¹⁸⁷ ). The remaining studies developed new assessment tools (n = 47; 38.5%) or did not describe the method used to assess GI symptoms (n = 9; 7.4%). The timeframe for recall of GI symptoms was not reported in 84 studies (68.8%), with other studies using varied recall periods ranging from less than or equal to a week (n = 6; 4.9%) to 3–12 months (n = 13; 10.7%).

Variables investigated

Included studies investigated a range of variables in association with GI symptoms in peri- and postmenopause (see Figure 4). These were categorised into: demographics, lifestyle factors, biomarkers, clinical markers and comorbidities, interventions, and menopause-related variables.

Figure 4.

Number of studies by variables investigated in research on GI symptoms in peri- and postmenopause, including comparisons by menopausal stage.

Created with Flourish. Available from: https://flourish.studio/. NB. Studies may include more than one comparison of menopausal stage.

PRE: premenopausal stage; PERI: perimenopausal stage; POST: postmenopausal stage; MT: menopausal transition.

Menopause-related variables were the most studied category (n = 60; 49.2%). This category included associations of GI symptoms with other menopausal symptoms (such as hot flushes; n = 6; 4.9%),^{74,92,105,107,144,155} years since the FMP (n = 2; 1.6%)^88,122 and rate of onset of menopause (n = 1; 0.8%). ¹³⁷ Comparisons of GI symptom frequency or severity by menopausal stage were observed in less than half of the included studies (n = 51, 41.8%). Symptom experience was compared in premenopausal with postmenopausal individuals in 43 studies (35.2%), while only three studies^31,34,182 (2.4%) made a comparison between perimenopausal individuals in the early and late MT.

Demographic variables were assessed in 18 studies (14.8%), with 8 studies (6.6%) considering the impact of age^{31,34,86,91,110,146,168,171} on the experience of GI symptoms in menopause. Ethnicity or race,^{115–117,119,120} type of occupation,^86,111,158 immigration status ¹¹⁸ and country of residence ¹¹² were also considered in the included studies.

With regard to studies investigating comorbidities and clinical markers (n = 27; 22.1%), mental health including perceived stress and anxiety,^{31,34,93,133,144,177} and menstrual symptoms (such as dysmenorrhoea and premenstrual syndrome)^{78,99,108,156,160,166} were both assessed in six studies, while other included studies considered associations with body mass index,^{79,91,130,150} obstetric history or complications during childbirth,^125,157,163 urinary disorders,^{28,135,138,161,183} other GI symptoms, ¹¹⁷ cardiovascular disease,^120,167 and bone health. ⁷³

Few studies examined lifestyle factors, with only one study each examining the relationship between GI symptoms and dietary intakes (tryptophan) ⁹¹ and physical activity. ⁷²

Included studies assessed biomarkers, including assays of sex hormones (n = 3; 2.4%),^31,34,91 stress hormones (n = 2; 1.6%),^31,34 genetic markers (n = 2; 1.6%)^141,142 and other assays such as urinary tryptophan, melatonin metabolites and serum allopregnalone (n = 3, 2.4%).^91,174,180

Discussion

This is the first scoping review to systematically map research on GI symptoms in ‘natural’ peri- and postmenopause. The most significant and most unexpected finding was the large volume (n = 122) of eligible studies identified, with a notable increase in publications in recent years. However, only 22 studies had a primary objective relating to GI symptoms in menopause. Furthermore, review findings highlight several methodological considerations and evidence gaps of interest to researchers and funders. These relate to the volume and conduct of research, and variables investigated, and are discussed further below. A summary of recommendations for future research is provided in Box 2.

Box 2.

Recommendations for future research.

Future studies should: • Investigate a range of GI symptoms in diverse sub-populations of individuals experiencing menopause (i.e. different races or ethnicities, and varied geographic locations) • Utilise standardised terminology and clearly report criteria used to determine menopausal stage of participants (e.g. STRAW + 106). • Assess GI symptoms with validated measures, with transparent reporting using appropriate timeframe and tools (e.g. mobile applications or digital diaries) to minimise recall bias and participant burden • Clearly report use of hormone replacement therapies, oral contraceptive use, hysterectomies, medical-induced menopause, providing separate GI symptom data for each group • Utilise longitudinal designs to assess the trajectory of GI symptoms across the menopausal transition and into postmenopause, facilitating comparison of GI symptom experience by menopausal stage • Conduct qualitative research to understand lived experiences of GI symptoms during peri- and postmenopause • Consider a range of correlates of GI symptoms (including psychological health and assays of sex hormones), controlling for potential confounding variables (e.g. age) • Evaluate the effectiveness of interventions for the prevention or management of GI symptoms during peri- and postmenopause

Volume of evidence

This review mapped studies to at least one of eight GI symptoms, ¹² with constipation being the most investigated symptom. While this review did not summarise study results, conflicting research findings^{27,29–31,35} combined with the large number of studies identified, suggest that constipation is a potential area for synthesis in a systematic review. In contrast, only four studies assessed vomiting in peri- or postmenopause. This may reflect the low prevalence of this symptom, or its omission from menopausal symptom scales commonly used in research.^{19–23,69,188–191} This is in contrast to symptoms such as constipation, diarrhoea, bloating, and abdominal pain, which feature in several instruments.^69,188–191 Alternatively, symptom reporting may be influenced by an individual’s stereotype of ‘the menopausal woman’, with symptoms only reported that are considered to be linked to the menopause (e.g. hot flushes), rather than all those experienced (i.e. vomiting). ¹⁹² These menopausal stereotypes could vary across cultures, with Im et al. ¹¹⁹ finding that while nausea and vomiting was documented in 18.9% of a sample of midlife women, reports of symptom frequency and severity varied by ethnicity. Interestingly, a recent study ¹⁹³ excluded from this review, found women placed high value on symptom relief from vomiting during menopause. However, it is not clear whether this study included individuals taking HRT, which could be a contributory factor in the aetiology of vomiting. ¹⁹⁴ Further research in diverse populations (i.e. varied ethnicities; HRT users vs non-users) and in consultation with menopausal individuals, may be warranted to determine if vomiting (and other GI symptoms) are indeed related to ‘natural’ menopause.

An important finding is the paucity of studies identified from South American and African countries, compared with Asian, North American and European regions. While this may be partly due to the exclusion of foreign language articles, an assessment of excluded publications indicates only a few non-English language studies were conducted in these regions. With evidence that there is ‘no universal menopausal syndrome’, ¹⁹⁵ and cultural or ethnic differences in menopausal symptom reporting, ¹⁹⁶ it is important that future research is conducted in varied locations to capture diverse experiences across cultures and geographies. This is consistent with findings of the recent Menopause Priority Setting Partnership ¹⁹⁷ which highlighted the need for research to explore menopausal symptoms across countries, cultures and ethnic backgrounds.

Conduct of studies

This scoping review revealed that qualitative research was notably underrepresented in this area, with only two articles identified.^163,176 This could be due to a focus in menopausal research on ‘known’ or clinically defined symptoms, rather than women’s actual experience of menopause. ¹⁹⁸ Qualitative research is important for capturing insights into lived experiences at different stages of menopause, the impacts of symptoms (e.g. on quality of life) beyond those on ‘established’ symptom checklists as well as the acceptability of different interventions for symptom management.^199–201 Furthermore, studies predominantly utilised quantitative cross-sectional designs (n = 89), as is consistent with findings of evidence syntheses assessing a diverse range of symptoms in menopausal research.^202–205 While cross-sectional study designs provide a convenient methodological approach for investigating symptom prevalence, it is difficult to draw causal inferences due to the measurement of exposure (i.e. menopausal stage) and outcome (i.e. GI symptoms) at a single timepoint.^206,207 Longitudinal studies are needed to assess the trajectory of symptoms across pre-, peri- and postmenopausal stages,^208,209 to differentiate pre-existing and new onset symptoms^210,211 and obtain accurate estimates of symptom durations. ²¹² However, this review identified only 14 longitudinal studies, and less than half of all included studies made a comparison of GI symptom experience across different menopausal stages. Only three studies compared GI symptoms in early versus late MT, despite evidence of differing menopausal symptomatology across these stages.^6,213 These findings highlight a need for further longitudinal research to effectively answer questions about the relationship between menopause and GI symptoms, as well as qualitative studies to better understand menopausal lived experiences.

Consistency in use of menopausal terminology and application of validated criteria for the classification of menopausal stages are key to understanding the impact of the MT on symptom experience, and to support comparisons of results from different studies.^61,214 However, the present review findings indicated that criteria for determining menopausal stage were not reported in over a third of studies, with only 13 studies citing STRAW or updated STRAW + 10 criteria.^6,184 Failure to document criteria for menopausal staging has been reported in previous research. ⁶¹ An alternative approach using age ranges as a proxy for menopausal stage was applied in nine studies; however, this strategy has been criticised ⁴⁰ due to the variability in age of MT and FMP. ²¹⁵ To strengthen the reliability and validity of future research, and minimise the risk of misclassification of menopausal stages, studies should utilise and clearly report validated criteria such as STRAW + 10⁶.

Similarly, review findings revealed that many studies did not use a validated tool to assess GI symptoms, with nine studies not reporting the measure used and 47 studies developing a study-specific tool. This issue has been noted in other reviews of menopausal symptoms more widely.^216–218 While it may be considered necessary to adapt measures for cultural appropriateness, it has been argued that validated tools are required to standardise data collection, and to facilitate rigorous comparisons between studies. ²¹⁹ Variation in the timeframe reported for symptom recall was also considerable: from not being described, to immediate capture on an app, or up to 12 months. This too is consistent with findings of evidence syntheses assessing other menopausal symptoms.^{216,217,220,221} Furthermore, 6-to 12-month recall periods could be too lengthy, limiting the accuracy of reporting of menopausal symptoms,^192,222 whereas daily symptom diaries may be burdensome for study participants. ²²³ Future studies should use validated measures to assess GI symptoms, identify appropriate tools (e.g. digital diaries or mobile applications) and timeframes for their recall, and clearly report details of measures used, as is also recommended by the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guidance. ²²⁴ This will support the synthesis of findings from multiple studies that could inform policy and practice.

Variables investigated

The diversity of factors and variables studied suggests there is limited agreement on those thought to be most important in influencing menopausal symptom presentation, as is also described in a scoping review of correlates of palpitations during menopause. ²²⁵ Multiple factors may influence ovarian function, hormonal levels and GI symptom experience, including ageing, dietary patterns, smoking, body mass index, psychological and social variables, and it is argued these should all be considered in menopause research.^117,213,222 The influence of ageing was only considered in eight included studies, despite evidence demonstrating the prevalence of GI symptoms such as constipation increases with age, ²²⁶ and psychological health was only considered in six studies. Furthermore, evidence gaps were identified, with no included studies assessing the impacts of smoking, sleep disturbances, or gut microbiome composition on GI symptoms in menopause. Interestingly, two ongoing studies^75,77 are investigating probiotic interventions in menopausal individuals with constipation and diarrhoea, implying that researchers believe there could be a role for changes to gut microbial composition in managing GI and other menopausal symptoms. With menopause occurring at a time of significant biological, psychological and sociocultural change, it is important that future research considers potential confounding variables and correlates to understand their impacts on GI symptoms. This may support the development of targeted lifestyle, behavioural or hormonal interventions for effective GI symptom management in peri- and postmenopause.

A summary of recommendations and methodological considerations for future research on GI symptoms in peri- and postmenopause is outlined in Box 2.

Strengths and limitations

This review employed comprehensive search methods to identify existing and ongoing research, with a good-practice systematic approach to the selection and mapping of evidence. However, several limitations should be noted. GI symptoms are often not well described in article titles/abstracts, and in consequence, relevant studies may not have been retrieved by database searches. That said, the use of supplementary searches, including citation-searching may have helped mitigate this issue. ²²⁷ With regard to review methods, a second reviewer screened 50% of records, and data charting was completed by a single author, and the potential for bias and human error is noted. Quality assessment of included studies is not a mandatory step in scoping reviews, ⁷⁰ and was not completed. While this may limit the review’s capacity to guide policy and practice, the review aim was exploratory, to identify gaps in the literature and inform future research.^70,228 In addition, due to time limitations and the large number of included studies, research assessing the role of HRT as a cause of, or as an intervention for, GI symptoms was excluded. With evidence that HRT use may influence the presentation of GI symptoms in menopausal women,^62,229–231 this is a key area that requires investigation in future reviews. As observed in other research on menopausal symptoms,^220,232 surgical menopause, HRT or oral contraceptive use was often poorly reported, or separate data not provided, making it challenging to identify studies of ‘natural’ menopause. Furthermore, it was often difficult to discern whether symptoms were of GI origin, for example, chest pain was excluded but may have been associated with heartburn. Similarly, abdominal pain may have either a GI or gynaecological aetiology (i.e. menstrual cramping). In order to discern the origin of symptoms, patient-reported outcome measures could gather additional data, for example, about the location of pain using visual tools, ²³³ temporal patterns (i.e. after eating, exertion or associated with menstruation), and co-occurring symptoms. ²³⁴ Finally, as the results of studies were not extracted, it is not possible to draw conclusions about the prevalence of GI symptoms in ‘natural’ peri- and postmenopause. This is an important area for future study.

Conclusion

This review mapped the available evidence on GI symptoms in ‘natural’ peri- and postmenopause to inform future research. While many studies were identified, findings highlighted few longitudinal and qualitative studies, insufficient reporting of criteria used to determine menopausal stage and data collection methods used to assess GI symptoms, and no studies investigating key variables that could influence symptom prevalence. In consequence, this review has identified evidence gaps and methodological considerations with implications for researchers, funders and priority setting partnerships. ¹⁰ Findings may help facilitate the prioritisation of future research and the design of new primary studies to best answer questions about GI symptoms throughout menopause, disentangling the interacting factors that contribute to their lived experience. Evidence syntheses relating to GI symptoms in those taking HRT, and in surgical or medical-induced menopause, would be a valuable addition to the findings presented here.