A metabolic view on menopause and ageing Original paper

What was studied?

The study focused on the impact of menopause on metabolic changes, particularly the effects of menopause on lipid and amino acid profiles, and their contribution to future cardiovascular and metabolic risks. It analyzed the metabolomic data from 26,065 individuals of Northern European ancestry, examining how menopause alters a broad spectrum of 135 serum metabolites, including lipoproteins, fatty acids, amino acids, and small molecules related to energy metabolism. The study aimed to assess the systemic metabolic shifts associated with menopause, considering not only traditional lipid measures but also detailed lipid subclass measurements and amino acid concentrations, which are emerging as key players in cardiovascular disease (CVD) and metabolic disorders.

Who was studied?

The study involved a large cohort of 26,065 participants, consisting of 16,107 Finnish individuals and 9,958 Estonian individuals. Participants were from a range of ages, predominantly from 40 to 75 years, with the analysis particularly focused on women in the menopausal transition (ages 40-55 years). The study excluded individuals using hormone replacement therapy (HRT), those with diabetes or on lipid-lowering medications, and pregnant women, to focus on natural metabolic shifts associated with menopause. The cohort was racially and ethnically homogenous, primarily consisting of individuals of Northern European descent, which may limit generalizability to other populations.

Most important findings

Postmenopausal women showed significantly higher concentrations of total cholesterol, esterified cholesterol, and lipoprotein subclasses, alongside higher concentrations of apoB and smaller, denser HDL particles. These changes align with increased cardiovascular risk. Higher levels of amino acids such as glutamine, tyrosine, and isoleucine were observed in postmenopausal women, which are linked to increased risk for metabolic diseases like Type 2 diabetes and cardiovascular diseases. Postmenopausal women exhibited increased levels of monounsaturated fatty acids and omega-7 and omega-9 fatty acids, which are associated with lipid metabolism and may influence CVD risk pathways. The study also found that a rapid increase in atherogenic lipid measures occurred between the ages of 45 and 50, coinciding with the onset of menopause, highlighting menopause’s role in altering lipid metabolism and contributing to long-term metabolic and cardiovascular risks.

Key implications

The findings from this study underline menopause as a pivotal factor influencing metabolic shifts that increase the risk of cardiovascular and metabolic diseases. The changes in lipid and amino acid profiles suggest that menopause accelerates a shift towards a pro-atherogenic state, which can predispose women to conditions like heart disease and type 2 diabetes. These insights are crucial for clinicians as they highlight the need for early monitoring of metabolic health during the menopausal transition. The study also emphasizes the importance of considering metabolic profiling, including lipoprotein subclass and amino acid measures, as potential biomarkers for future cardiovascular risk in postmenopausal women. Additionally, the role of menopause in influencing fatty acid metabolism suggests that interventions targeting diet and lifestyle may be necessary to mitigate these risks.