Menstrual blood as a research biospecimen: a scoping review protocol

Abstract

Introduction

Although systemic blood testing is usually used for research, it is invasive and may limit accessibility and participant compliance. Menstrual blood is usually discarded but contains whole blood and diverse biomarkers with relevance to reproductive and systemic health. Evidence shows an overlap between menstrual and systemic blood, with additional unique biomarkers that may enhance research. Despite this, menstrual blood remains under-represented in research and no scoping or systematic reviews are currently available on this topic.

Methods and analysis

This review will include peer-reviewed studies involving menstruating individuals from whom menstrual blood was collected for research. Eligible studies must examine menstrual blood collection methods, analytical approaches, feasibility or acceptability, biomarker identification and outcomes across any research setting.

The search will be conducted in MEDLINE (Ovid), Embase (Ovid) and Web of Science Core Collections, without date or language restrictions. Screening of titles, abstracts and full texts will be performed in Covidence alongside the inclusion criteria. Data will be extracted using a standardised form capturing information on research purposes, the population, collection methods, sample handling, key outcomes and challenges. Extracted evidence will be summarised following JBI methodology and Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) reporting standards.

Ethics and dissemination

Ethics approval was not required. The findings will be disseminated through publication in a peer-reviewed journal and conference presentations.

Trial registration number

This scoping review protocol has been registered with OSF (https://osf.io/prq3g/).

STRENGTHS AND LIMITATIONS OF THIS STUDY.

• This scoping review follows established JBI methodology and Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) reporting standards, enhancing transparency, reproducibility and quality.

• A comprehensive search across multiple major databases without date or language restrictions increases the breadth of captured evidence.

• Use of standardised screening and data extraction processes ensures consistency and methodological rigour.

• Limiting inclusion to peer-reviewed literature may result in the exclusion of relevant grey literature and emerging evidence.

Introduction

Blood tests provide critical insights into various physiological aspects of the body and are fundamental to monitoring changes that advance research and inform clinical decision-making.^1–3 Systemic blood or serum samples remain the conventional approach for diagnosis, monitoring and research.¹ However, obtaining a specimen from the body in this way is invasive, potentially causing pain and anxiety.^{1 3 4} Such discomfort results in poor compliance and reluctance in obtaining capillary blood samples, which may lower participation in research studies.¹ Furthermore, traditional venous blood analysis often requires additional preprocessing, such as anticoagulation, dilution or separation of blood components, which can limit its practicality for simple, low-cost point-of-care monitoring.¹

The menstrual cycle has the potential to provide accurate information across women’s lifespan and advance women’s health research.⁵ Despite approximately 1.8 billion people menstruating every month, menstrual blood is typically discarded and remains significantly under-represented in research.¹ Menstrual fluid is a composite biological material containing whole blood, vaginal secretions and cellular components shed from the endometrial lining and cervix during the late secretory phase of the menstrual cycle.^{3 6–8} In the absence of implantation, menstrual fluid includes proteolytic enzymes, cytokines, apoptotic markers and numerous proteins derived from immune cells that are an integral part of menstruation.^{6 7} This complex composition provides a unique and rich source of biomarkers that could offer valuable insight into both reproductive and systemic health.

Emerging evidence suggests that menstrual blood can serve as a non-invasive alternative to traditional venous blood sampling.^{4 9} Research shows that menstrual blood shares 548 proteins with systemic blood, while also containing 385 unique additional proteins and biomarkers within its complex profile that enrich its potential as a research specimen.1 3 4 6 Specifically, progestogen-associated endometrial protein, glycogen phosphorylase, small proline-rich proteins, ADP/ATP translocase 2 and keratin type II cytoskeletal 7 have been consistently identified in menstrual blood, allowing it to be easily distinguished from venous blood regardless of ethnicity, age or use of hormonal contraception.⁸

Although largely overlooked, a preliminary search has shown that using menstrual blood-based testing can be an alternative to systemic blood analysis currently in practice, improving convenience, accessibility and reduced invasiveness of blood analysis, particularly for women’s health applications.^{3 4 10} New collection technologies have the potential to enhance participant compliance in blood sampling and reduce barriers associated with menstrual blood collection. Innovations such as MenstruAI are an example of a wearable, pain-free monitoring device that is integrated into hygiene pads for biomarker detection.¹ This alternative may also improve health research in developing countries or resource-constrained settings where there is limited access to medical equipment and professionals.^{1 3} Nonetheless, potential barriers and challenges remain regarding the implementation and acceptability of menstrual blood collection methods, including discomfort with menstrual cups for sample collection.³ Menstrual stigma and culturally or religiously rooted taboos may also influence perception of menstruation and the willingness to collect or provide menstrual blood samples.¹¹

Regardless of its apparent accessibility, biochemical richness and potential research value, menstrual blood remains a largely unexplored biological sample in research. Preliminary searches of MEDLINE and Embase identified no existing or underway scoping or systematic reviews on this topic. Therefore, a scoping review is warranted to examine the extent and characteristics of the existing literature on menstrual blood collection for research purposes and to identify knowledge gaps that may guide future investigations.

Methods and analysis

This protocol describes a scoping review aimed at identifying and mapping existing studies that use menstrual blood as a biospecimen for research. A scoping review methodology was chosen to comprehensively map the existing evidence on this topic and identify key knowledge gaps for future research. The proposed scoping review will be conducted in accordance with the JBI methodology for scoping reviews.¹² The Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines will also be followed to report this study.¹³ Any protocol modifications will be documented in the final manuscript.

The review is planned to start in May 2026 and is expected to be completed September 2026.

Review questions

1. What methods and technologies have been described in the literature for collecting menstrual blood as a biological specimen for research purposes?

2. In what contexts and study designs has menstrual blood collection been implemented, and what collection procedures were used?

3. What types of analysis have been conducted using menstrual blood samples, and what biomarkers or outcomes have been identified or measured?

4. How do studies evaluate the acceptability, feasibility and validity of menstrual blood collection for research compared with conventional blood sampling methods?

5. What challenges, barriers or limitations have been reported in implementing menstrual blood collection for research applications?

Inclusion criteria

Population

This scoping review will consider studies involving biological females who menstruate, regardless of age, ethnicity or gender identity, from whom menstrual blood has been collected for research purposes. Studies may include participants who are healthy or living with a health condition, provided menstrual blood was used as a biological specimen. Publications involving only non-human samples will be excluded.

Concept

The scoping review will examine concepts that include, but are not limited to, the collection, use and analysis of menstrual blood as a biological specimen for research applications. Eligible publications may describe:

1. Methods, techniques or technologies used for menstrual blood collection.

2. Laboratory analysis or processing procedures of menstrual blood samples, including biomarkers, proteomic, metabolomic or cellular analysis.

3. Feasibility, acceptability, validity and reproducibility of menstrual blood as an alternative to conventional systemic blood sampling.

4. Reported outcomes, biomarkers and research applications of menstrual blood.

Context

This scoping review will include studies conducted in any setting or geographic region, including clinical, laboratory, academic and community-based environments. No geographic limitations will be applied.

Types of sources

This scoping review will consider articles strictly limited to peer-reviewed published literature, including research projects, reviews, pilot studies and protocols. Textbooks, opinion papers and conference abstracts will not be included in this scoping review.

Search strategy

The search strategy is designed to identify all relevant published literature. Keywords and controlled vocabulary terms will be searched for the following concepts: menstrual blood/fluid and collection (including terms such as sampling and analysis). The search strategy, including all identified keywords and index terms, will be consistent for each included database and/or information source (see online supplemental appendix I). The reference list of all included sources of evidence will be screened for additional studies.

The databases to be searched include MEDLINE (Ovid), Embase (Ovid) and Web of Science Core Collection (Science Citation Index, Emerging Sources Citation Index). Unpublished studies and grey literature will not be included in the search.

Studies published in any language will be included. If a paper appears relevant, we will seek a translation at the full-text screening stage to ensure accurate data extraction.

The MEDLINE, Embase and Web of Science searches can be found in online supplemental appendix I.

There will be no date restrictions for the search on any database.

Study/source of evidence selection

Following the search, all identified citations will be collated and uploaded into Covidence, a bibliographic software, to store, organise and manage all the references used, as well as identify and remove duplicate records.¹⁴ Titles and abstracts will then be screened to determine whether they meet the predefined inclusion criteria for the review. Potentially relevant sources will be retrieved in full and will be assessed in detail against the inclusion criteria to confirm their suitability. Any studies excluded at the full-text stage, along with the reasons for their exclusion, will be documented and reported in the scoping review. The overall search and selection process will be fully detailed in the final scoping review and illustrated using a PRISMA-ScR flow diagram.¹⁵

Data extraction

Data will be extracted from papers included in the scoping review using a standardised extraction form developed to capture details from the relevant literature included. Extracted data will include specific details about participants, study location, context, study methods and key findings relevant to the review questions.

A draft of the extraction form to be used for the scoping review is provided (see online supplemental appendix II). The draft data extraction tool may be refined throughout the data extraction process to ensure it captures all the necessary information. Modifications will be detailed in the final manuscript. When needed, study authors may be contacted to obtain missing or clarifying information.

Data analysis and presentation

Extracted data from the reviewed studies will be summarised and categorised in a table format (online supplemental appendix II) to directly address the primary research objectives and review questions. Specifically, results will be grouped under the following analytical domains: publication summary; research purpose; population; menstrual blood collection method; sample handling; key outcomes and findings; challenges and limitations; other. Other visual representations (eg, diagrams, charts, etc.) may also be used to illustrate topics.

Ethics and dissemination

As this is a scoping review protocol, ethics approval is not applicable. All datasets, appendices, and detailed search strategies will be made publicly available on completion of the scoping review to ensure transparency and reproducibility. The findings will be disseminated through publication in a peer-reviewed scientific journal and shared more broadly through presentation at a scientific conference and inclusion in conference proceedings.

Ethics statements

Patient consent for publication

Not applicable.