Hormone Replacement Therapy for Menopausal Symptoms and the Risk of Cardiometabolic Disease: Current Evidence and Future Directions.

Abstract

BACKGROUND The transition through menopause is accompanied by a series of adverse metabolic changes which are associated with an increased risk of cardiometabolic disease, a major cause of mortality in women after midlife. Whilst the indication for menopausal hormone replacement therapy (HRT) is the control of menopausal symptoms, understanding and discussing the cardiometabolic impacts of HRT are necessary to facilitate informed decision-making at treatment initiation and continuation, and to select appropriate regimens. METHODOLOGY A narrative review. RESULTS Existing evidence suggests that HRT is likely to impact the development of metabolic risk factors including visceral fat accumulation, adverse changes in lipid profile, blood pressure and glycaemic control. Findings from randomised controlled trials have refined our understanding of the impact of HRT on cardiometabolic outcomes including coronary heart disease and stroke. Furthermore, recent research has highlighted the impact of the menopause on the development and severity of metabolic dysfunction-associated steatotic liver disease (MASLD) that has been poorly studied in the context of HRT. The route of oestrogen administration, timing of initiation and type of progestogen are all likely to affect the impact of HRT on many of these outcomes. There has recently been extensive media interest in HRT in some countries resulting in increased prescription rates. Understanding the impact of HRT on cardiometabolic risk is therefore particularly important. In this narrative review, we discuss the existing evidence and clinical guidelines on the effect of HRT on cardiometabolic risk factors and the risk of coronary heart disease, stroke and MASLD, highlighting areas of uncertainty and priorities for further research.