Hormone Shift in Menopause Contributes to Cardiovascular Risk in Aging Women

New research from a team of investigators in Europe suggests hormonal changes during menopause could explain up to 10% of the increase in LDL-C associated with the transition to menopause among aging women.

An analysis of data from more than 200 women in a prospective study, results of the study suggest the hormonal shift in 17β-oestradiol (E2) and follicle-stimulating hormone (FSH) levels among women transitioning from perimenopause to early postmenopause was associated with proatherogenic circulating metabolome alterations, with these metabolite shifts were partially ameliorated with hormone replacement therapy (HRT).

“Menopause is unavoidable but it is possible that the negative metabolite shift can be diminished by eating healthily and being physically active,” said study investigator Eija K. Laakkonen, PhD, associate professor of Gerontology and Public Health of the University of Jyväskylä in Finland, in a statement. “In particular, women should pay attention to the quality of fat in their diet and getting sufficient exercise to maintain cardiorespiratory fitness. HRT is an option that women should discuss with healthcare providers at this point in their lives.”

With previous data establishing the menopausal transition as a period often associated with a negative change in cardiometabolic health biomarkers, Laakonen and a team of colleagues sought to further explore these associations beyond clinical biomarkers using metabolomics to assess the effect of the menopausal transition on circulation metabolite. Using data from the Estrogenic Regulation of Muscle Apoptosis (ERMA) prospective cohort study, investigators obtained data related to a cohort of 234 Finnish women followed through the menopause transition who kept a menstrual diary during follow-up and underwent laboratory assessments of FSH levels every 3 or 6 months until early postmenopause. After the application of further inclusion criteria, which included not reaching menopause, unknown menopause status, and inconsistent HRT use, a total of 218 participants were identified for inclusion in metabolomics analyses. Of these 218 women, 35 started HRT during the study.

The mean age of participants at first measurement was 51.7 (SD, 1.9) years and the median follow duration was 14 (IQR, 8-20) months, with an overall range of 4 months to 3.5 years. Of the 35 women who started HRT during the study, 27 received oral therapy and 8 received transdermal HRT.

Investigators included a pair of exploratory analyses in their study. The first metabolomic analysis assessed the direct and indirect associations, measured via body fat percentage change, between the menopausal hormonal shift and metabolite changes in the 183 women experiencing natural menopause using latent change score modeling. The second analysis assessed the association of HRT initiation during follow-up with the metabolite measurements was studied in the entire study cohort using menopausal status and HRT interaction as the exposure.

In adjusted analyses, the concentration of ApoB (0.17 SD [99.5% CI, 0.03 to 0.31), very-low-density lipoprotein triglycerides (0.25 SD [99.5% CI, 0.05 to 0.45]) and particles (0.21 SD [99.5% CI, 0.05–0.36]), LDL-C (0.17 SD [99.5% CI, 0.01 to 0.34]) and particles (0.17 SD [99.5% CI, 0.03 to 0.31]), HDL triglycerides (0.24 SD [99.5% CI, 0.02–0.46]), glycerol (0.32 SD [99.5% CI, 0.07 to 0.58]) and leucine increased (0.25 SD [99.5% CI, 0.02 to 0.49]). Additionally, citrate (−0.36 SD, CI −0.57 to −0.14) and 3-hydroxybutyrate concentrations decreased (−0.46 SD, CI −0.75 to −0.17).

Further analysis demonstrated most metabolite changes were associated with the menopausal hormonal shift, which explained 11% and 9% of the LDL-c and particle concentration increase, respectively. Investigators also pointed out menopausal hormone therapy was associated with increased medium-to-large HDL particle count and decreased small-to-medium LDL particle and glycine concentration.

“This study links hormonal changes during menopause to metabolic alterations that promote heart disease. Previous studies did not confirm menopausal status with hormone measurements, meaning that they could not differentiate menopausal effects from aging. Our results should be interpreted with caution, since the links with sex hormones and HRT were found in exploratory analyses and need confirmation,” added Laakkonen.

This study, “Menopause modulates the circulating metabolome: evidence from a prospective cohort study,” was published in the European Journal of Preventive Cardiology.