PhD Studentship via the GW4 BioMed2 MRC Doctoral Training Programme

Rationale

Problematic menstrual symptoms such as heavy menstrual bleeding (HMB) are common and distressing, impacting substantially on quality of life and mental wellbeing of affected women. As well as this likely effect of HMB on poor mental health (MH), there could also be an effect in the reverse direction: psychological stress is also a known disruptor of menstrual cycles and can be associated with heavier bleeding. Additionally, HMB is almost always self-reported and measured subjectively (with reduced quality of life now being part of the official diagnosis), so an association between HMB and MH might be explained by women with mood disorders being more likely to assess their level of bleeding as abnormal and substantially affecting their quality of life.

Both HMB and MH are influenced by inflammation. Increasing evidence suggests that inflammation plays a causal role in the pathogenesis of psychiatric disorders, including depression, and inflammation is also known to show cyclical variation, partly influenced by fluctuations in reproductive hormones throughout the menstrual cycle. There is also some evidence that systemic and local endometrial inflammation is associated with severity of menstrual symptoms like HMB.

Aims & Objectives

This project aims to explore direct effects of HMB on MH, and of MH on HMB, as well as the potential confounding or mediating role of inflammation. A better understanding of these relationships would help inform ways to predict whether women with HMB are at greater risk of MH conditions, and whether women with MH conditions are at greater risk of menstrual issues like HMB. This would help clinicians tailor care to improve outcomes for groups of women. Understanding whether these associations are likely to be causal, and whether inflammation plays a role in the manifestation of both HMB and MH conditions will help shed light on the pathogenesis of HMB (and underlying pathologies) and MH and suggest whether both could be effectively treated using anti-inflammatory medications.

Methods

This project will use a genetic epidemiology approach to examine bi-directional associations between HMB and MH, as well as the role of inflammation in explaining any relationship. The student will first examine the association between HMB and MH phenotypes in UK Biobank and the Avon Longitudinal Study of Parents and Children (ALSPAC). Then, using results from our previous genome-wide association study (GWAS) of HMB in UK Biobank, the student will generate polygenic risk scores (PRS) for HMB in UK Biobank and ALSPAC and conduct reduced-phenome-wide association studies (PheWAS) to identify MH variables and inflammatory biomarkers associated with genetic liability to HMB. The student will also use LD score regression (LDSR) to explore the genetic correlation between all traits of interest using our HMB GWAS results and results from previously published GWAS of MH conditions and inflammatory biomarkers. Any associations from the pheWAS and LDSR will be followed up using Mendelian Randomization (MR) to explore if relationships are likely to be causal.

The student will learn to apply 2 MR approaches: 1) 1-sample MR (this will allow us to test MR assumptions using individual-level data), 2) 2-sample MR using GWAS summary statistics (this will improve power above the one sample MR).

Sensitivity analyses will allow the student to explore assumptions of both methods.

The student will also explore effects in the opposite direction by using results of previous GWAS of MH conditions and inflammatory biomarkers to generate PRS in ALSPAC and UK Biobank and test for associations with HMB, as well as in 1 and 2 sample MR analyses to explore causality.

The student will triangulate findings from across the PRS and MR analyses to inform network MR analysis including HMB, MH and inflammation to explore the strength and direction of direct and indirect and combined and independent causal effects.

How to apply

Student applications can be made via the GW4 BioMed2 website: https://www.gw4biomed.ac.uk. The closing date for applications is 5pm on Friday, 26th November 2021. Shortlisted applicants will be invited for an informal interview (over the phone, on Skype or Zoom) between Monday 31^st January 2022 and Friday 11th February 2022. The formal interviews will be held virtually on the 16^th and 17^th February 2022.

A GW4 BioMed2 MRC DTP studentship includes full tuition fees at the UK/Home rate, a stipend at the minimum UKRI rate (£15,609 for 21/22), a Research & Training Support Grant (RTSG) valued between £2,000-£5,000 per year and £300 annual travel and conference grant based on a 3.5-year full-time studentship. These funding arrangements will be adjusted pro-rata for part-time studentships.

The GW4 BioMed2 MRC DTP studentships are available to UK, EU and International applicants. The GW4 institutions have all agreed to cover the difference in cost between home and international tuition fees. This means that International candidates will not be expected to cover this cost.

For any informal queries about the studentship, please contact Gemma Sharp (gemma.sharp@bristol.ac.uk).

Women are nearly three times more likely to suffer from common mental health disorders than men, and this risk is highest during their reproductive years. Hormonal fluctuations and symptoms associated with the menstrual cycle are likely to form complex, multidirectional associations with mental health. However, the intersection of menstrual and mental health is severely under-researched leaving millions of women with limited support and treatment options.

Below, we outline some of the ways in which menstrual and mental health could be linked.

Menstrual disorders

Symptoms of menstrual disorders, such as abnormally heavy or prolonged bleeding (menorrhagia), pelvic pain (dysmenorrhea), irregular cycles and menstrual cessation (amenorrhea), are associated with lower quality of life and wellbeing, non-attendance at school and work, and higher rates of mental health disorders.

Stigma and a lack of knowledge about what is ‘normal’ means menstrual disorders are often under-reported and under-diagnosed, particularly in low and middle income countries (LMICs), but they affect a large proportion of the population. For example, in LMICs, one study found that 5-20% of women experienced period pain that prevented usual activities. In the UK, 5% of women aged 30-49 years (that’s over 439,380 women) consult their GP each year due to excessive uterine bleeding.

The association between menstrual disorders and mental health is likely to be extremely complex, involving interactions between genetics, reproductive hormones and other physiological processes, but also environmental factors including lifestyle and social, political and structural influences on health and wellbeing, which will vary between high income countries (HICs) and LMICs. The association is also likely to be bidirectional. We already know that psychological stress can impact the menstrual cycle, causing changes to menstrual cycle features like heaviness of bleeding and regularity, as well as amenorrhea.

Menstrual health management

Access to safe, clean facilities, affordable menstrual products and sexual and reproductive healthcare are important factors in shaping women’s experiences around menstruation, and unmet menstrual health needs can have significant impacts on mental and social wellbeing. Taboo, stigma, and shame associated with menstruation can compound effects of these unmet needs on menstrual health. Most menstrual health management interventions are focused on providing menstrual products to individuals, but do little to tackle the structural and societal factors that reinforce menstrual stigmas and create barriers to menstrual health (Thomson et al., 2019).

Mental health over the menstrual cycle

Reproductive hormones, like oestrogen, progesterone and gonadotrophins (LH and FSH), fluctuate throughout the menstrual cycle, and this can have pronounced effects on physiology, mood and wellbeing. Premenstrual syndrome (PMS) is a set of symptoms that often occur about a week or two before menstruation (in the luteal phase of the cycle), and can include bloating, breast tenderness, swelling in hands and feet, food cravings, difficulty sleeping, as well as changes to mood and feeling upset, irritable or anxious. Premenstrual Dysphoric Disorder (PMDD) is a mental health disorder that can impact a person’s ability to work, socialise and have healthy relationships. PMDD patients may experience suicidal thoughts premenstrually.

A better understanding of the mechanisms linking the menstrual cycle to mental health could help to identify women who might benefit from woman-centred psychological therapy (focused around self-acceptance and self-care) or hormonal treatment rather than interventions traditionally used to treat mental health issues, like antidepressant medication.

Menarche

The first occurrence of menstruating is called menarche. During this time, huge hormonal changes can affect mood and mental health. It can be a confusing time, and social stigma and taboo around menstruation can make important conversations difficult. Early negative feelings and experiences around menstruation could act as a blueprint for future, so quality education at this time (for menstruating adolescents and their non-menstruating peers) might help to reduce confusion and stigma, and improve mental wellbeing.

The average age at menarche varies significantly by geographical location and demographic factors like ethnicity. An earlier menarche has been linked to an increased risk of depression in adulthood, but the mechanism is unknown. It could involve a biological predisposition, but psychosocial factors and experiences in adolescence are also likely to play a role.

Menopause

The other end of the female reproductive life course is marked by the cessation of menstruation at the menopause. Hormonal changes around this time result in a wide range of physical symptoms including increasingly irregular menstrual cycles with changes to the duration and amount of bleeding, as well as symptoms like hot flushes, sweating, vaginal dryness and insomnia. Psychological symptoms are also common, including anxiety, depressive mood, irritability, mood swings and loss of libido. Cognitive symptoms include an inability to concentrate and poor memory. All of these physical and mental symptoms can affect a woman’s ability to have a good quality of life, to socialise, maintain relationships, and work, all of which is all tied up with good mental health.

Recognising and understanding the link between menopause and mental health is important for helping peri-menopausal women and their families and friends make sense of these changes, which are often completely normal and not do not indicate any kind of pathology. If healthcare providers were better able to predict which women were most at risk of experiencing mental health issues around menopause, they would be able to offer extra support to them. A better understanding of the biological and social factors that cause some women to suffer with their mental health at this time would help in the development of new treatments and strategies to lower women’s risk and improve their mental health.

In September, we held three workshops to discuss our ideas further. Each workshop was based on a different theme that had emerged from our previous discussions in June. We also invited some stakeholders from Public Health England and the mental health charities Mind and Off the Record to one of our workshops. The discussions were very fruitful and we have some much clearer ideas of the research questions we would like to address (and how we might address them). We’re now preparing for our next events: a stakeholder engagement event and a writing retreat.

As with our June workshops, we were delighted to have illustrator Laura Sorvala live scribe our discussions!

Melanie Channon

I’m a demographer and social statistician working mainly in low and middle income countries. I was recently PI on a project that looked at issues of menstrual taboos and menstrual policy in Nepal. As part of this project we looked at the association between menstrual taboos and mental health and psychosocial wellbeing.  I’m particularly interested in issues relating to measurement and conceptualisation of menstruation (especially given that menstrual health is excluded from the SDGs). I’m also interested in the impact menstruation has on everyday life and how this might directly impact mental health.

I’m currently involved in a project looking at menstrual health (and broader SRHR) of migrants returning from the USA to Latin American countries.

I’ve worked on demographic and public health issues affecting Nepal since 2007, including sex-selective abortion, fertility, and son preference.

• Twitter @frostyallyea

Dr Jennifer Thomson 

My core research and teaching interests are in gender and politics, broadly defined. My current work focuses on:

• gender and foreign policy, and particularly the concept of a ‘feminist’ foreign policy;
• the Women, Peace and Security agenda;
• women’s rights in post-conflict divided societies;
• sexual and reproductive health and rights in international policy-making.

Dr Fran Amery 

My research addresses the intersection of social movement activity and policy and legislative processes, particularly around gender and LGBTQIA equality. A key focus has been reproductive justice and abortion in the United Kingdom. My recent book, Beyond Pro-Life and Pro-Choice (Bristol University Press, 2020) traces the history of abortion politics from the passage of the 1967 Abortion Act, to contemporary debates around decriminalisation, disability rights and sex-selective abortion. 

It was great to meet each other (although still online rather than face-to-face unfortunately) at our first workshop last week.

The aim of the workshop was to learn more about each other and start to generate ideas about how we might conduct research together in the area of menstrual and mental health.

By the end of the workshop, we initially aimed to have:

• A list of (roughly prioritised) research questions/ideas
• A list of potential stakeholders (people who would be interested in and/or benefit from our research) to invite to the next workshop (in September)

Through lots of interesting talks and discussions, we got some way to achieving these aims, and we also had a much better idea of how we might work together on collaborative research. The main outcome was that we identified a need to develop specific themes to focus on. We each have broad interests, and a broad range of stakeholders might be interested in different aspects of our research. We need to develop focussed themes, but take care to achieve a balance around focus vs multidisciplinarity (i.e., we don’t want to make themes based around disciplines – that would defeat the point of multidisciplinary research!). Once we have a better idea of general themes, we’ll have a better idea of which stakeholders to invite to our stakeholder workshop in September. We’re looking forward to this workshop – we all agree that it will be important to involve stakeholders in co-designing research relatively early, before ideas are fully developed. 

An illustrator, Laura Sorvala, summarised each day of our first workshop as a “live-scribe” from recordings. We’re so happy with how these turned out! We hope to have Laura involved in our future workshops, and we can highly recommend her for other academic meetings. We were so impressed with how quickly she produced this work and how accurately she summarised our workshop – much nicer and more engaging than boring typed minutes!

Gemma Sharp

I’m a Senior Lecturer in Molecular Epidemiology, with a long-standing interest in reproductive biology and women’s health. Most of my previous research has been focused around pregnancy, for example my PhD was on pregnancy complications and the molecular pathways behind childbirth. More recently, I have begun a series of research projects looking at the epidemiology of menstrual function and dysfunction and the impact of menstruation on women’s broader health and quality of life. As with many areas of women’s health, understanding in this area is severely limited, and considering the huge number of people affected, the area is under-researched. I’m very much looking forward to trying to rectify this by working with the multidisciplinary GW4 Menstrual and Mental Health Research Community.

Twitter: @ammegandchips

Abigail Fraser

I am a Professor of Epidemiology with an interest in women’s reproductive health. Reproductive health is an important health domain in its own right. It is also a useful marker of women’s overall health and well-being, providing opportunities to identify women at increased risk of ill-health and to intervene to reduce this risk. I look forward to working with a diverse and multidisciplinary group of researchers to improve young women’s reproductive and mental health.

Twitter: @abifraser1

Gemma Sawyer

I am currently a Master student at the University of Bristol studying Public Health and am set to begin a PhD examining the relationship between menstrual symptoms and socioeconomic disadvantage later on this year. I am interested in menstrual health and its relation to mental health as they are both complex and important issues that affect a great number of people and are relatively under-researched. I am excited to be a part of this community early in my academic career to learn from its work and members.

Kayleigh Easey

I am a postdoc within the MRC IEU at the University of Bristol. My research focuses on reproduction and the potential causal effects of parental prenatal health behaviours on offspring health. I have a background working in mental health both in research and applied settings, and am interested in finding and reducing pathways to such harm. Menstrual health can have a huge impact on many areas of life, yet there is a lack of funded research investigating this. I am particularly interested in bringing awareness to this area and establishing pathways from menstrual disorders to mental health, to ultimately develop better support and treatment options for women.

• Twitter: @KayEasey

Kate Bowen-Viner

Kate is a Social Policy PhD student at the University of Bristol. Her PhD focuses on Relationships Education, Relationships and Sex Education and Health Education in England and how education can help to tackle menstrual stigma. Kate has a career background in education. She has been a secondary school teacher, a civil servant (Department for Education) and a senior associate at the Centre for Education and Youth (CfEY). Kate’s experience of working in the education sector has contributed to her interest in the intersection between young people’s experience of menstruation, their mental health and wellbeing and stigmatising menstruation discourses. She is particularly interested in working with young people to tackle the context-specific menstrual stigma that they experience in their lives.

• Twitter: @KateBV

Lindsey Pike

I work to support research-policy engagement and impact. I’m interested in how we can ensure that policy and practice decisions are informed by the best available evidence, and take account of issues related to equality and diversity. The Department for Health & Social Care’s Women’s Health Strategy provides a timely opportunity to highlight and focus on gendered issues such as menstruation and mental health, and I’m looking forward to thinking the implications of this work through with the team.

• Twitter: @Lindsey_Pike

Tigist Grieve

I am a Lecturer and researcher at the University of Bristol. My background is in International Development. My research interest encompasses inequalities and questions of social reproduction with particular interest on adolescent girls’ SRHR, welfare and wellbeing in Africa. My recentresearch work includes Burkina Faso, Ethiopia, Sierra Leone, Somalia, and Uganda. A recent project where I was a PI can be found here Unheard voices of girls in Africa. Ienjoy bringing my research and practical insights into teaching to enrich students experience and exposure to relevant real-world issues. As a pracademic I am also incredibly well positioned in seeing research uptake by NGOs in informing appropriate interventions.

I am particularly interested in an interdisciplinary approach to adolescent girls wellbeing and SRHR.

In academic setting, I am the co-lead of the Faculty of Social Sciences and Law International Development Research Group- FSSL-ID. I am also a board member at the Bristol Poverty Institute – BPI and a Visiting Fellow of Centre for Development Studies (CDS) at the University of Bath.

Beyond academia I engage in informing policy and practice with valuable evidence to disrupt inequality and intergenerational transfer of social and economic disadvantages. I am a Trustee of Bristol based Charities, the Southwest International Development Network (SWIDN). I am also the founder of a small charity, For-ethiopia www.for-ethiopia.com and the Mullers Charitable Foundation, based in Bristol.

Twitter @TigistGrieve

Rebecca Richmond

I am a Vice Chancellor’s Research Fellow in Molecular Epidemiology. My major areas of focus are on the large-scale integration of molecular data in population-based and clinical health science as well as the development and application of causal inference methods, including Mendelian randomization. I have specific interests in cancer and sleep research. I would like to explore in greater depth the links between reproductive and menstrual conditions and cancer development, as well as the interplay between sleep and women’s health.

Gemma Ford

I am a lecturer and the programme lead for the taught MSc in Reproduction and Development in the Bristol Medical School: https://www.bristol.ac.uk/medical-school/study/postgraduate/reproduction-development/ I was awarded a Needham Cooper CASE Scholarship which enabled me to study for a PhD in Neuroendocrinology at Bristol and GlaxoSmithKline, looking at the effects of stress and metabolism on hypothalamic neuropeptides. I then moved to Galway, Ireland for my postdoctoral research, maintaining my interest in stress and neuroendocrinology, but also extending my interests into pain medicine and affective disorders. My current teaching and research interests are in the area of reproductive endocrinology, and my research focuses on understanding the mechanisms underpinning the reciprocal relationship between stress and anxiety, nutrition, reproduction and pain.

Maria Fannin

I am a feminist health geographer with an interest in reproductive politics. Most of my research in this area has focused on changing understandings of pregnancy and childbirth over time and the different forms of expertise and knowledge shaping how these processes are experienced. For the last decade, I have carried out qualitative research on tissue donation and use (especially reproductive tissues such as umbilical cord blood, placenta, and menstrual blood but also peripheral blood). I am particularly interested in how research on mental and menstrual health can play a role in transforming medical and cultural norms about women’s bodies and the bodies of people who menstruate.

Other members

Laura Howe, Sarah Sullivan, Deborah Lawlor, Carol Joinson, Sinead English, Doretta Caramaschi, Hannah Jones

Anna Murray

Anna Murray works in the field of reproductive genomics. She is particularly interested in discovering genetic variants associated with reproductive lifespan that can further our understanding of the biological processes involved. The group also use genetic variants associated with traits such as menopause timing as instruments to make causal inferences for outcomes such as breast cancer and type II diabetes. Other projects are using a combination of genomic and non-genetic risk factors to predict women at increased risk of early menopause.  

• Twitter: @AnnaM1966

Kate Ruth

My work has included carrying out genome-wide analyses of reproductive traits including reproductive lifespan, menstrual cycle length and sex hormone levels. In these studies we investigate correlations between genetic variation and phenotypes by analysing data in many thousands of people. Applying these genomic methods provides an opportunity to improve our understanding of the biology of such traits and our knowledge of how different disorders are related to each other. We can also use the genetic signals found by our studies to identify reproductive disorders that cause, rather than are correlated with, health outcomes. I am also interested in how we can use routinely collected health data to explore the genetic basis of reproductive traits, for example, by analysing data from big population-based studies with linked health data like UK Biobank. For example, my previous work highlighted that lower follicle stimulating hormone levels are linked to longer menstrual cycle length and that there are overlaps with the genetics of other reproductive traits.

• Twitter: @kate_s_ruth

Jess Tyrrell

Jess Tyrrell uses genetics to research the complex links between metabolic health and mental health. Depression and mental health problems are more prevalent in women. Some studies have suggested links between menstrual health and mental health in women, although these relationships remain poorly understood. We are using genetic methods to test the relationship between a number of menstrual factors (e.g. sex hormones, menarche age and menopause age) and well validated mental health outcomes, including treatment resistant depression.

• Twitter: @JSTyrrell

Julia Prague

I am an NHS Consultant in Endocrinology, Diabetes, and General Internal Medicine at the Royal Devon and Exeter Hospital and Honorary Senior Clinical Lecturer at the University of Exeter. My PhD was in reproductive endocrinology and particularly focused on the menopause and finding a new treatment for menopausal vasomotor symptoms that avoids the side effects of HRT.

• Twitter: @julia_prague

Welcome to the online home of the Menstrual and Mental Health Research Community.

This research community was established to facilitate collaborative research into how the menstrual cycle interacts with mental health. All community members are based at one of the four GW4 universities: Bath, Bristol, Cardiff and Exeter.

You can read more about why we set up this community on our About page.