Life course epidemiology of women's reproductive health and its relation to chronic disease

Reproductive health is important to a woman's overall health and well-being and is increasingly recognised as a marker for other diseases that she might experience later on in life. However there are gaps in our knowledge about what causes some women to have poorer reproductive health, for example, have highly irregular menstrual cycles, difficulties getting pregnant, or experience hot flashes and night sweats around menopause. I propose to answer these gaps. I will use information from several large studies that include many women, some of which have collected information on women since they were in the womb or since their birth. I will use this information to find out what affects their reproductive hormone levels, their menstrual patterns and how easy it is for them to get pregnant in early adulthood, and how likely they are to have complications of pregnancy. This is important as some of the causes of poor reproductive health may be preventable. Also, women are increasingly having children at older ages and it is important that we understand what affects women's chances of getting pregnant and having a healthy pregnancy. There are also gaps in our understanding of why women with poorer reproductive health, including complications of pregnancy, such as pre-eclampsia, are more likely to have other diseases later in their life such as heart disease. Here too I will use large studies of older women, to find out why some women with poorer reproductive health are more likely to have heart disease, diabetes, breast cancer and other diseases later in life. Understanding the relationship between women's reproductive health and other diseases is important as it may identify potential new treatments. I will also assess whether information about reproductive health which women accurately and easily remember can be used to accurately predict their chances of having diabetes, heart and bone disease and dementia later in life. This is important as women at high risk can then be offered advice or treatment that will lower that risk.

Reproductive health is important to a woman's overall health and well-being and is increasingly recognised as a sentinel for chronic disease in later life. However important knowledge gaps in the life course epidemiology of female reproductive health and in the understanding of the nature of its relation to chronic disease remain. Here I will study multiple exposures from foetal life to adulthood in relation to reproductive health and potential as measured by reproductive hormones in early adulthood, a critical time for family planning. I will use information on multiple reproductive indicators such as menstrual cycle characteristics, parity, pregnancy complications, gynaecological disorders and their treatment, to better characterize women's reproductive health. I will study relations between these reproductive indicators (separately and in combination), reproductive hormones and major chronic disease outcomes (including breast cancer, cardiovascular disease, diabetes, osteoporotic fractures, depression, dementia, and lung disease) and disease markers to study causality and identify mechanistic pathways. Finally, I will examine whether readily available information on indicators of female reproductive health can improve risk stratification in women. I will use data from multiple complimentary studies and a variety of analytical approaches to identify causal pathways, as well as novel statistical methods to formally compare different life course models of the relationship between early life exposures, reproductive health and later disease outcomes. This work has the potential to inform preventive strategies, to identify treatment targets for female reproductive health as well as related chronic diseases, and to improve risk stratification in women at increased risk of diabetes, cardiovascular disease, osteoporosis and dementia. This is important because most are preventable or have a better prognosis if treated earlier and all are costly to health services.

The aims of this research are to identify the determinants of women's reproductive health and potential in early adulthood, and to clarify whether women's reproductive health is causally related to several major diseases that are prevalent in women and if so, to identify the causal pathways. This has the potential to impact on the following groups of beneficiaries in the short to medium term, i.e. during the life of this fellowship:
1. A wide range of scientists investigating disease mechanisms. As the work proposed here aims to study the aetiology of women's reproductive health and its potential contribution to a range of major disease outcomes, findings may inform the work of colleagues investigating the aetiology of reproductive health but also of breast cancer, cardiovascular disease, diabetes, dementia, depression and lung disease using various approaches from investigations at the molecular level, through to population based approaches.
2. Researchers using a life course approach, as the work proposed here will contribute to developing novel statistical methods to compare different life course models.
3. Both myself and the appointed researcher on this project will gain immediate skills which are particularly relevant to research but that are also transferable and applicable in other contexts. These include skills in project management including people and data management, programming, and communication skills.
Beneficiaries in the medium and longer term, i.e. both during and beyond the life of the fellowship include:
4. Ultimately the goal of this research is to improve the well-being and health of women worldwide. Through better understanding of what affects women's reproductive health and potential; how their reproductive health contributes to the risk of major disease outcomes; and how readily available information on women's reproductive health can be used to identify women at risk of chronic disease, the work proposed here can inform preventive strategies, identify potential treatment targets, as well as ensure more effective provision of care. Improving our understanding of what affects reproductive health and potential in early adulthood can inform women's family planning as well as estimates of future demand for assisted reproduction technologies. By improving the accuracy and/or simplifying existing risk prediction scores, women at increased risk of a range of diseases can be identified and offered effective interventions to prevent, treat and manage their risk. By clarifying the role of pregnancy complications in shaping CVD risk, the management of women who experienced a pregnancy complication in the post-partum period can be improved and potential treatment targets can be identified. More effective risk stratification and healthcare provision is also likely to be of economic benefit to health service providers and to society in general.
5. National and international bodies responsible for issuing clinical guidance on organisation and management of care, screening policies and the use of risk prediction models, such as the UK Royal College of Obstetricians and Gynaecologists and the National Institute for Health and Care Excellence.