NEW $50M Program in Women’s Health

the
missed
vital sign

Download the full program announcement here

Every minute, somewhere in the US, a woman requires a blood transfusion because of her menstruation. Heavy menstrual bleeding (HMB) often involves blood loss so significant that if it was associated with an injury, it would result in a call for an ambulance or a trip to the emergency room. HMB is reported by 1 in 3 women and is more common than asthma or diabetes in reproductive aged women. It causes adverse health conditions like anemia, and it negatively impacts emotional and financial wellbeing. Girls miss school – women can’t go to work. And yet, HMB is largely ignored by society, healthcare professionals and researchers. The result? Currently, women suffer for an average of 5 years before getting help.

Women need better solutions. We need to routinely record and quantitatively measure menstruation so that it is no longer The Missed Vital Sign. Menstrual parameters provide a unique signal of overall health for women, generally, and are critical to identification, diagnosis and treatment of HMB, specifically. We need to close the gap in our biological understanding of the fundamental mechanisms that occur when the uterine lining (the endometrium) breaks down, sheds, and repairs at menstruation. In this program, we intend to demonstrate the advances in women’s health that are possible when menstruation is treated as a vital sign – our goal is to reduce the time it takes a woman to get effective treatment for HMB more than tenfold – from 5 years to 5 months.

What is the problem?

Menstruation provides unique information about the health of half the population* – it indicates the presence or absence of gynecology conditions, such as leiomyoma (fibroids) or adenomyosis, as well as wider health issues like thyroid disease, bleeding disorders, and pituitary tumors.

Despite its importance as an indicator of overall health, current clinical practice in the UK is that menstruation is only routinely asked about and recorded by women’s health specialists, estimated to be less than 10% of all healthcare consultations. The result is that significant health conditions go undiagnosed, untreated, and millions of reproductive-aged women are in health crisis before they are helped.

For example, HMB is reported by 1 in 3 reproductive-aged women when directly asked as part of research1,2 – this rate is 10 times that of asthma or diabetes in the same population. Up to 50% of reproductive aged women are iron deficient, that is up to 950 million women globally, with chronic HMB expected to be a major contributor.3 Iron deficiency causes fatigue, shortness of breath, and difficulty concentrating. If HMB is left untreated, iron deficiency can progress to iron deficiency anemia, which at its most severe will necessitate blood transfusion.

Across the globe, girls routinely miss school due to their menstruation, with an average of 9 days lost per girl per year in the UK; compared to 7.8 days for coughs and colds and 3.6 days due to truancy.4 This equates to a loss of 11 academic weeks due to menstruation per girl across the formative teenage years and girls. In the US, it is estimated that there are more than 100M school absences per year due to menstruation. Girls with HMB are one third less likely to achieve the minimum grades needed for apprenticeships and further education than those without HMB.5 Women with HMB miss work an average of 3.6 working weeks annually,6 costing the US economy >$94 billion every year. Experiencing HMB is associated with rates of anxiety and depression that are three times the average of the broader female population.7,8

At best, HMB is life restricting, at worst, it can be life threatening. And it is a symptom that affects more women for longer than ever before. A few centuries ago, women experienced just over 100 menstrual cycles in their lifetimes. On average, they had 5 children and lactated for 12 months with each child. Today, women living in high resource settings can expect to menstruate over 400 times, due to a combination of extended reproductive lifespan and reduced pregnancy and lactation. Menstruation always was an important sign, but it is more relevant to women’s lives today than ever before.

What are the limits of current practice?

Despite its frequency, prevalence, and negative physical, emotional and financial effects, women endure HMB for an average of 5 years before getting effective treatment.9 This is due to delays in identification, diagnosis, and suitable treatment.

Taboos surrounding menstruation result in HMB being normalized by women and society. Further, not all menstrual loss is blood, meaning women cannot conveniently or accurately quantify the volume of their menstrual blood loss, compare it to population averages, or determine levels that put them at risk. Self-perception of menstrual blood loss has sensitivity and specificity values of only 60-70%.10 This, combined with the insidious onset of adverse health effects such as iron deficiency, means that 50% of women with HMB have never sought help. Those who do take an average of 3 years to present.7 And when they do present, healthcare providers lack the tools needed to identify HMB, meaning 84% of women who seek help feel dismissed.11 The combined result is that only 8% of women who suffer with HMB are accessing the tests and treatments required to alleviate it.

Things don’t get much better once HMB is identified. We know that structural conditions such as leiomyomas and adenomyosis are associated with HMB,12 but a survey of women in the UK in 2020 revealed that 40% had required more than 10 appointments to diagnose leiomyoma.7 Currently, there are no diagnostic tests that can be performed by women or their primary care physicians. Service pressures slowing access to specialists have therefore added to diagnostic delays. For example, the number of women waiting for specialist gynecology input in the UK has doubled since the COVID pandemic.13

Perhaps more concerning, in approximately half of women with HMB, no underlying structural condition is identified. Indeed, we still do not understand the fundamental mechanisms that result in HMB when the endometrium breaks down, sheds, and repairs at menstruation. This lack of biological understanding means the mainstay of current treatment is fertility removing surgery or hormonal medication, which can completely override natural ovarian hormone production. Exogenous hormones have intolerable side effects for many women, meaning 50% change medical treatments within 1 year. And up to 60% eventually opt for surgery.14

Our goal.

The goal of The Missed Vital Sign program is to demonstrate that routine recording, quantifiable measurement, and better treatment options for menstruation can reduce the time a woman experiences heavy menstrual bleeding from 5 years to 5 months. We aim to do this without increasing unwanted surgical intervention or menstrual cycle suppression.

To achieve the goals of the program, we seek advances in 3 thrust areas.

To ensure women get effective treatment within 5 months, we must optimize each part of the pathway. Firstly, methods to identify women with HMB must do so within 3 months of onset and be scalable across different ages, geographies, cultures, abilities and demographics to ensure reach. In parallel, we must define the underpinning endometrial causes of HMB sufficiently to conduct high-throughput screening to identify new non-hormonal treatment targets and validate them so that they can progress to clinical trials. In addition, for speed and personalization of treatment, new point-of-care diagnostics to determine the cause of HMB and presence of any associated conditions are required for effective treatment to be provided within 2 months of presentation. Whilst acknowledging the significant negative impact of HMB on social, emotional and material quality of life, this program focuses on the mitigation of physical harm, with the aim of catalyzing diagnostic and treatment breakthroughs for all women with HMB.

Thrust 1. A high-performance multivariate tool to identify women who have HMB at levels that would result in iron deficiency, ensuring they access help within 3 months not 3 years.

Iron deficiency is the first manifestation of physical harm from chronic heavy menstrual bleeding. Therefore, this tool should have an accuracy of >80%, as determined by the area under the curve (AUC) in a receiver operating characteristic (ROC) curve across diverse populations and ages. It should not require specialist training and be scalable to home and/or community healthcare settings such that screening can reach at least 60% of women globally. This would enable the identification of over 91M women with HMB at levels that lead to iron deficiency within 3 months. To achieve this, biomarkers of HMB that will result in iron deficiency must be developed, validated and combined with environmental, behavioral and demographic factors to predict and stratify women at risk of physical ill health from their menstruation.

Thrust 2: Identify causal factors for HMB to inform diagnostic development and identify new, precise, non-hormonal therapeutic targets, particularly those that could be self-administered.

Currently, we estimate that 316M women globally seek help for HMB. If 84% are dismissed, approximately 50M women currently access specialist investigations and treatment for HMB. If identification of HMB causing iron deficiency is robust and accurate, the number of women requiring clinical management will almost double (91M). Without developing new diagnostics and treatments for HMB in parallel, large numbers of women will leave the clinic undiagnosed, without effective treatment, and still at risk of iron deficiency. To ensure effective treatment within 2 months of presentation, we need to identify the factors that cause the endometrium to bleed heavily at menstruation to inform diagnostics and develop precise treatments that are tailored to women’s needs.

Thrust 3. Develop and validate patient stratification tools to personalize management when HMB is identified and ensure effective treatment. This would mean women get treatments that work for them within 2 months, not 2 years.

Advances across the three thrusts should inform each other to improve and validate predictive markers for HMB, underlying conditions and endometrial cause to stratify women and personalize management. It is not necessary to form large consortiums or teams to do this – it will be facilitated by Wellcome Leap to make progress together towards the program goals.

Download the full program announcement here

Program Director.

Jackie Maybin, MD, PhD, is a Reader and Honorary Consultant Gynaecologist at the Centre for Reproductive Health at the University of Edinburgh and NHS Lothian. She leads a specialist menstrual disorders service, providing both medical and surgical treatments. Her research focuses on developing preventive and therapeutic strategies for problematic menstrual bleeding, with a particular interest in the role of hypoxia in endometrial function. Dr. Maybin holds a Wellcome Clinical Career Development Fellowship to investigate these mechanisms. She served on the editorial boards of several journals, including Reproduction, Journal for Endometriosis and Uterine Disorders, and Physiological Reviews. Additionally, she is the past president of the RCOG Blair Bell Society, a member of the Royal Society of Edinburgh’s Young Academy of Scotland and chairs the National Menstrual Clinical Network for the Scottish Government.

Call for abstracts and proposals.

We are soliciting abstracts and proposals for work over three (3) years in one or more of the following thrust areas (see Thrust areas in full program announcement). Proposers should clearly relate work in these thrust areas to one or more of the program goals.

It is not necessary to form a large consortium or teams to address all facets of the program. The strength of this approach will manifest through program-level integration of efforts from individuals and small agile teams with deep (and sometimes narrow) expertise. Across all projects, Wellcome Leap will facilitate iterative and collaborative integration of findings to refine models and improve and validate predictive measures and adapt approaches as teams make progress towards shared goals.

Process and timeline
Program announcement.

30 DAYS FOR PREPARATION AND SUBMISSION OF ABSTRACT

15-Day Abstract review round.
/ Day 1
Submission deadline: 16 May 2025
/ Day 15
Abstract feedback sent: 31 May 2025
All submissions will receive technical and/or programmatic feedback as well as a recommendation to submit or not submit a full proposal.

30 DAYS FOR PREPARATION OF FULL PROPOSALS AFTER ABSTRACT FEEDBACK

30-Day Full proposal review round.
/ Day 45
Submission deadline: 30 June 2025
25-page full proposals including technical approach, milestones, costs, and key personnel submitted. Proposals should specifically address abstract feedback.
/ Day 75
Proposal decision sent: 30 July 2025

All submissions will receive a ‘selected for funding’ or ‘not selected for funding’ decision. Those selected will proceed to contract signature as the final gate with work expected to commence within approximately 30 days.

Mechanics of applying

Who is eligible?

Performers from universities and research institutions: small, medium, and large companies (including venture-backed); and government or non-profit research organizations are invited to propose.

Wellcome Leap accepts project proposals from any legal entity, based in any legal jurisdiction, including academic, non-profit, for-profit, and regulatory/professional organizations. Applicants are encouraged to contact Wellcome Leap about joining its Health Breakthrough Network by executing its MARFA (or CORFA for commercial entities) agreement. Full execution of the Wellcome Leap MARFA is not required for application submission but is required for any award.

Wellcome Leap agrees not to use any confidential information disclosed to it in a submitted proposal for any purpose other than the review of a proposal. Wellcome Leap will not use the information contained in a proposal for Leap’s direct or indirect personal or financial benefit and will not make such information available for the direct or indirect personal or financial benefit of any other organization or individual.

Wellcome Leap shall not disclose or permit disclosure of any confidential information with anyone who has not been officially designated by Leap to participate in a review and completed a confidentiality agreement. Wellcome Leap agrees that it shall take all reasonable measures to protect the secrecy of and avoid disclosure or use of confidential information in order to prevent it from falling into the public domain or the possession of unauthorized persons. Such measures shall include, but not be limited to, the same degree of care that Wellcome Leap utilizes to protect its own confidential information, which shall be no less than reasonable care. Wellcome Leap further agrees to promptly notify in writing of any actual or suspected misuse, misappropriation, or unauthorized disclosure of submitted confidential information which may come to Leap’s attention.

Notwithstanding the above, Wellcome Leap shall have no liability with regard to any information which Leap can prove:

(i) was in the public domain at the time it was disclosed or has entered the public domain through no fault of Leap;

(ii) was known to Leap, without restriction, at the time of disclosure, as demonstrated by files in existence at the time of disclosure;

(iii) is disclosed with the prior written approval of the submitter;

(iv) becomes known to Leap, without restriction, from a source other than Leap without breach of this statement; or

(v) is disclosed pursuant to the order or requirement of a court, administrative agency, or other governmental body; provided, however, that Leap shall provide prompt notice of such court order or requirement to submitter to enable submitter to seek a protective order or otherwise prevent or restrict such disclosure.

Furthermore, please recognize that Wellcome Leap may already by funding, or considering funding, the same or similar technology as covered by a submitted proposal—or have previously received from third parties—information or proposals similar to that which was submitted, that was not subject to confidentiality.

Wellcome Leap’s adherence to the above use of confidential information shall continue for a period of three (3) years from the receipt date of a submitted proposal.

Full proposal application steps.

  1. Download guidelines
  2. Download full proposal template (and cost and schedule template)
  3. Upload your full proposal and submit your application between 23 June 2025 and 30 June 2025, 11:59pm ET.

Frequently asked questions.

If you have questions, please review our FAQ section here. – updated 15 May 2025.

  1. Fraser, I. S. et al. Prevalence of heavy menstrual bleeding and experiences of affected women in a European patient survey. International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics 128, 196-200, doi:10.1016/j.ijgo.2014.09.027 (2015).
  2. Sinharoy, S. S. et al. Prevalence of heavy menstrual bleeding and associations with physical health and wellbeing in low-income and middle-income countries: a multinational cross-sectional study. Lancet Glob Health 11, e1775-e1784, doi:10.1016/S2214-109X(23)00416-3 (2023).
  3. Munro, M. G. et al. The relationship between heavy menstrual bleeding, iron deficiency, and iron deficiency anemia. Am J Obstet Gynecol 229, 1-9, doi:10.1016/j.ajog.2023.01.017 (2023).
  4. Breaking the Cycle, https://www.phs.co.uk/media/l5idzgti/breaking-the-cycle.pdf (2023).
  5. Sawyer, G., Fraser, A., Lawlor, D. A., Sharp, G. C. & Howe, L. D. Associations of adolescent menstrual symptoms with school absences and educational attainment: analysis of a prospective cohort study. medRxiv, 2024.2004.2024.24306294, doi:10.1101/2024.04.24.24306294 (2024).
  6. Cote, I., Jacobs, P. & Cumming, D. Work loss associated with increased menstrual loss in the United States. Obstetrics and gynecology 100, 683-687 (2002).
  7. Heavy Menstrual Bleeding, breaking the silence and stigma, https://static1.squarespace.com/static/5ccc3b392727be60b3a02ec3/t/5e5e1c515406da1b393d470c/1583225943688/HMB_Report+02.03.20.pdf (2020).
  8. Weyand, A. C. et al. Depression in Female Adolescents with Heavy Menstrual Bleeding. J Pediatr 240, 171-176, doi:10.1016/j.jpeds.2021.09.007 (2022).
  9. Warner, P. et al. Low dose dexamethasone as treatment for women with heavy menstrual bleeding: A response-adaptive randomised placebo-controlled dose-finding parallel group trial (DexFEM). EBioMedicine 69, 103434, doi:10.1016/j.ebiom.2021.103434 (2021).
  10. Magnay, J. L., O’Brien, S., Gerlinger, C. & Seitz, C. A systematic review of methods to measure menstrual blood loss. BMC Womens Health 18, 142, doi:10.1186/s12905-018-0627-8 (2018).
  11. Women’s health – ‘Let’s talk about it’ survey. (2022).
  12. Munro, M. G., Critchley, H. O. D., Fraser, I. S. & Committee, F. M. D. The two FIGO systems for normal and abnormal uterine bleeding symptoms and classification of causes of abnormal uterine bleeding in the reproductive years: 2018 revisions. International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics 143, 393-408, doi:10.1002/ijgo.12666 (2018).
  13. Waiting for a way forward: Voices of women and healthcare professionals at the centre of the gynaecology care crisis, https://www.gov.uk/government/calls-for-evidence/womens-health-strategy-call-for-evidence/outcome/3fa4a313-f7a5-429a-b68d-0eb0be15e696 (2024).
  14. RCOG. National Heavy Menstrual Bleeding Audit: Final Report. (2014).

    *The program is intended to benefit and catalyse research for anyone suffering with heavy menstrual bleeding.

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