Cardiovascular Risk of Menopausal Hormone Therapy in Women with Diabetes: A Cohort Study

Study type
Protocol
Date of Approval
Study reference ID
24_004133
Lay Summary

Diabetes is a condition where our body has trouble controlling blood sugar levels, resulting in high blood sugar. High blood sugar increases the risk of stroke, heart attack, and clots in blood vessels. These problems are often called cardiovascular disease (CVD). In women, the risk of CVD further increases during and after menopause. Menopausal Hormone Therapy (MHT) is commonly used to treat menopausal symptoms. We know that the use of MHT can increase the risk of CVD in the general population, but we do not know if MHT increases the risk of CVD even more in women with diabetes. We plan a study to find out if MHT changes the risk of CVD in women who were diagnosed with diabetes between 2004 and 2024. We will look for the medical records of all women aged between 40 and 65 years with a diagnosis of diabetes. This will be our study population. Next, we will divide the study population into two groups: those who took MHT and those who did not. Then, we will compare the risk of heart attack, stroke, and blood clot in each group. We will use Clinical Practice Research Datalink (CPRD) medical information that has been anonymised before being made available for research. Our study results will inform women with diabetes about the long-term effects of MHT, allowing them to make informed choices about treatment options for menopausal symptoms.

Technical Summary

Approximately two million women in the UK are affected by diabetes, with 44% of diagnoses occurring during midlife (40-65 years). Diabetes increases the risk of cardiovascular disease (CVD), and this risk further increases for women during and after menopause. Small clinical studies suggest that the use of Menopausal Hormone Therapy (MHT) may mitigate the potential excess risk of CVD in women with diabetes. There is a lack of large population-based studies that have investigated the risk of CVD in menopausal women with diabetes prescribed MHT. Our objectives are to 1) describe the prescribing rate of MHT in women with diabetes by type and treatment of diabetes, age, ethnicity, and Body Mass Index (BMI) and 2) assess the risk of CVD (VTE, MI and stroke) in women with diabetes who are prescribed MHT.

We will use data from CPRD to establish a cohort of women (40-65 years), diagnosed with diabetes and with CPRD follow-up time between 2004 and 2024. Women in receipt of prescriptions for MHT will be our exposed population. We will select a subset of women with 'non-exposed' follow-up time from the study cohort and use exposure density sampling (EDS) to assign a random index date for the comparison group (non-users). A Cox regression model will be used to compare the incidence of outcomes between MHT ever-users and non-users. Our analyses will be run separately by type of diabetes and MHT treatment and take into account factors that may influence our results, such as age, BMI, and ethnicity. Propensity scores will be used to control for potential confounding, and several sensitivity analyses will be performed to assess the robustness of our results.

Our study results will contribute to evidence-based MHT prescribing for menopausal symptoms in women with diabetes.

Health Outcomes to be Measured

Venous thromboembolism (VTE); Myocardial infarction (MI); Stroke

Collaborators

Ruth Brauer - Chief Investigator - University College London ( UCL )
Hindun Risni - Corresponding Applicant - University College London ( UCL )
Kenneth Man - Collaborator - University College London ( UCL )
Li Wei - Collaborator - University College London ( UCL )

Linkages

HES Admitted Patient Care;ONS Death Registration Data;CPRD Aurum Ethnicity Record;Patient Level Townsend Index