Women in healthy transition deep phenotyping cohort study protocol (KiSO-DP): a within-participant multidisciplinary...

Cardiovascular disease risk accelerates in women after the menopausal transition, coinciding with the cessation of endogenous oestrogen production. The accompanying decline in vascular function is considered a key driver of this shift. However, longitudinal studies investigating the impact and time course of changes in cardiovascular and skeletal muscle function during the menopausal transition and in the subsequent years are warranted.

The Women in Healthy Transition (KiSO) Deep Phenotyping (DP) study is a multidisciplinary prospective longitudinal cohort study with the objective to determine cardiovascular changes from the late reproductive stage through 20 years of postmenopause. The primary outcome is quantification of endothelium-dependent vascular function. Secondary outcomes include evaluating endothelium-independent vascular function, conduit artery endothelial function, mitochondrial function, circulating skeletal muscle vascular markers and sociological factors. The overall aim is to provide deep mechanistic, longitudinal insight into menopause-related vascular ageing to inform future cardiovascular disease prevention strategies in women.

200 healthy women will be examined at the late reproductive stage and at 1, 3, 5, 10 and 20 years postmenopause. At each test round vascular function is evaluated using invasive intra-arterial infusion protocols, including acetylcholine and epoprostenol infusions, as well as flow-mediated dilation. Additional measures include arterial blood pressure, arterial compliance, echocardiography, cardiorespiratory fitness, whole-blood rheology, dual-energy X-ray absorptiometry-derived body composition, circulating reproductive and cardiometabolic biomarkers, skeletal muscle biopsies for assessment of mitochondrial capacity and proteins related to skeletal muscle and cardiometabolic health. Menopausal staging is determined using Stages of Reproductive Aging Workshop (STRAW)+10 criteria supported by follicle-stimulating hormone, anti-Müllerian hormone concentrations and antral follicle count.

The study is conducted in accordance with the Declaration of Helsinki and has been approved by the regional ethics committee: Ethics Committee of Copenhagen (H-22025286) and is registered with ClinicalTrial.gov (NCT05647876). Findings from the study will be disseminated through publications in peer-reviewed scientific journals, presentations at national and international conferences and through PhD theses. The results are expected to provide novel insights into the development of vascular and skeletal muscle function across the menopausal transition and may contribute to future strategies for prevention of cardiovascular disease in women.

NCT05647876.