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.
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.