Metabolic

Menopause ‘metabolomic fingerprint’ associated with worse lipid profile

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The authors report no relevant financial disclosures.

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Hormonal changes during the menopause transition are associated with a “proatherogenic metabolomic fingerprint” that modulates lipoprotein and lipid metabolism, including significant changes in HDL and LDL, researchers reported.

In an analysis of longitudinal data that included measurement of 180 metabolites, researchers also found that the use of menopausal hormone therapy may modify such changes, specifically increases in HDL and reductions in LDL.

Graphical depiction of data presented in article

Data were derived from Karppinen JE, et al. Eur J Prev Cardiol. 2022;doi:10.1093/eurjpc/zwac060.

“Taken together, our findings link menopause to a deterioration of cardiovascular and metabolic health,” Eja K LaakkonenPhD, associate professor of gerontology and public health at the University of Jyväskylä, Finland, told Healio. “Our results consistently indicate that menopause modulates lipoprotein and lipid metabolism towards a proatherogenic direction and that the menopausal hormonal shift leads to a metabolic signature indicative of deteriorating insulin sensitivity.”

Monitoring menopause transition

Eja K Laakkonen

Laakkonen and colleagues analyzed longitudinal data from 218 perimenopausal women not using hormone therapy (HT) at baseline who were participating in a prospective cohort study in Finland (recruitment in 2014-2015). Researchers monitored women for menopause transition via menstrual diaries and serum measurements of estradiol and follicle-stimulating hormone (FSH). Researchers also assessed levels of 180 lipids, lipoproteins and amino acids at baseline and every 3 to 6 months until postmenopause, which was defined as amenorrhea for at least 6 months and elevated FSH levels on two consecutive measurements. Researchers also assessed menopausal HT use at each follow-up visit. The mean baseline age was 52 years; median follow-up was 14 months.

The findings were published in the European Journal of Preventive Cardiology.

Within the cohort, 35 women initiated menopausal HT during the study. Women who initiated HT were younger than nonusers at the first measurement, had lower FSH levels and lower systolic and diastolic BP.

Researchers found menopause was associated with a change in 85 metabolite measures. The concentration of apolipoprotein B increased by a mean 0.17 standard deviation (SD; 99.5% CI, 0.03-0.31), resulting from an increase in VLDL and an increase in LDL particles.

Cholesterol concentrations in all ApoB-containing classes increased from 0.17 to 0.2 SD. The increase in VLDL triglycerides (mean, 0.25 SD; 99.5% CI, 0.05-0.45) and HDL triglyceride concentrations (mean, 0.24 SD; 99.5% CI, 0.02-0.46) was more pronounced, according to researchers.

“Total serum fatty acid concentration did not change, but the fatty acid profile shifted from polyunsaturated to saturated direction,” the researchers wrote.

Menopause shift, metabolite changes

Researchers found that the menopausal hormonal shift directly explained the change in 64 of the 85 metabolites identified as menopause-responsive in the primary analysis, with effect sizes ranging from 2.1% to 11.2%. Results persisted after adjustment for baseline age, duration of follow-up, education level, smoking status, alcohol use, physical activity and diet quality.

“This study links hormonal changes during menopause to metabolic alterations that promote heart disease,” Laakkonen said in a press release. “Previous studies did not confirm menopausal status with hormone measurements, meaning that they could not differentiate menopausal effects from aging.”

A second exploratory analysis suggested HT use was associated with increases in HDL and reductions in LDL; however, Laakkonen said strong conclusions cannot be drawn due to the small number of women who initiated HT.

“Based on our results and results from some earlier studies, menopausal HT positively affects LDL and HDL metabolism and decreases glycine concentrations,” Laakkonen told Healio. “However, very strong conclusions cannot be drawn solely based on our observational study since the number of women starting HT was small and the type of HT was not controlled. This is an issue that should be studied further.” “

For more information:

Eja K Laakkonen, PhD, can be reached at eija.k.laakkonen@jyu.fi; Twitter: @eija_laakkonen.

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