Summary
During the postmenopausal stage women often display adverse lipid profiles; however, evidence is insufficient regarding the association between lipids and reproductive aging in Korean women. Bearing this in mind, Park et al. [1] aimed to characterize lipid changes in relation to the timing of menopause in 1,436 Korean mid-aged (premenopausal) women who had a natural menopause during the follow-up period (median = 15.76 years) from the Korean Genome and Epidemiology Study (KoGES) Ansan and Anseong cohort. Lipid levels were measured every 2 years, and the magnitudes of annual lipid changes and differences in the changes by premenopausal body mass index were estimated using piecewise linear mixed-effects models. The authors found that all lipid levels increased greatly from 3 or 5 years before menopause to 1 year after menopause in all women, regardless of their premenopausal body mass index (BMI). During the period, HDL-C levels increased at 0.42 mg/dL per year (95% CI, 0.29 to 0.55). Nevertheless, non-HDL-C levels simultaneously increased at 3.42 mg/dL per year (95% CI, 3.11 to 3.72), and an annual change in the non-HDL-C to HDL-C ratio was 0.05 (95% CI, 0.04 to 0.06). One year after menopause, changes in all lipid parameters significantly slowed down, except for the non-HDL-C to HDL-C ratio (p < 0.001 for all). The ratio continued to increase until 3 years after menopause, but thereafter, the change leveled off. The researchers conclude that women experienced remarkable increases in lipid levels during menopausal transition, highlighting the need for early intervention strategies for cardiovascular disease (CVD) prevention in women.
Commentary
Worldwide, CVD is the leading cause of mortality. In 2019, approximately 17.9 million people died from CVD, corresponding this to 32% of all global deaths. Despite the fact that men are at higher risk for CVD, after the menopause, due to estrogen deficiency, women are prone to have higher rates of CVD [2]. During the transition to the menopause, due to a decline in ovarian function and estrogen secretion, women are subject to bio-psycho and social changes that can impair their quality of life. More importantly, after menopause, CVD risk increases significantly, partly due to estrogen deprivation. In fact, an increase in weight and other factors such as sedentary lifestyle, dietary habits, among others, negatively impact metabolic parameters, making women more susceptible to CVD events [3]. There are several studies that suggest that estrogens have a positive effect on female lipid profile and vasculature due to their antioxidant effect, gene modulation expression and the regulation of the inflammatory pathways [4]. Therefore, predicting CVD in women during the perimenopausal stage is crucial in order to prevent related deaths.
To date, there has been much focus on the changes of lipids after the menopause onset, which would thus increase CVD risk. In this sense, the present study of Park et al. [1] characterized lipid changes in relation to years since menopause yet examined differences in the patterns of changes according to premenopausal BMI using a Korean community-based prospective cohort. The authors found a notable increase in lipid levels from 3 or 5 years before menopause to 1 year after menopause. According to the authors a previous cross-sectional analysis of Korean women aged 44–56 years similarly reported an increase in the values of lipid parameters across menopausal stages, except for HDL-C. Substantial increases occurred between early and late menopausal transition for triglycerides, LDL-C, non-HDL-C, and Apo B levels and between late transition and postmenopause for triglycerides levels [5]. Interestingly, increases in lipid levels during the menopausal transition were observed even in under- and normal-weight women [5]. These results are similar to the findings of Park [1] in that irrespective to their baseline weight there is an increase in atherogenic lipid levels. Moreover, increase during the transition was more evident in women with lower weight than in heavier ones.
The authors mention that their study has some limitations. First, repeated measurements of reproductive hormones and novel lipid metrics, such as HDL subclasses and function, were not available for the current analysis. Second, they measured lipid levels only after the age of 40 years. Future studies should examine lipid values at younger ages, which may be useful to decide the timing of lifestyle interventions in order to prevent increases in lipid levels during female midlife. Third, the current analysis included menopausal status as a binary variable because menopausal stages based on menstrual cycles and bleeding patterns were examined only in later follow-up years. Future studies should consider detailed menopausal stages based on the regularity of menstrual cycles and bleeding patterns, as the onset age and duration of the menopausal transition might influence changes in lipid levels during the transition. Also, medical history including medications were self-reported and not verified from other sources like medical reports or prescriptions. Finally, their study population included relatively healthy Korean mid-aged women. Therefore, differences in race/ethnicity and health status should be considered when generalizing their results to other populations.
Despite these limitations, Park and collaborators [1] mention that to the best of knowledge, their study is the first to document changes in non-HDL-C levels and non-HDL-C to HDL-C ratio with years since menopause, including a large number of observations with sufficient follow-up measurements of lipids and controlled for multiple potential covariates associated with lipid changes during the menopausal transition.
I agree with the authors, in accordance to their results, that lipid changes should be regularly monitored since the premenopausal stage, regardless of their body weight. Indeed, finding a remarkable increase in lipid levels before women reach the menopause suggests the importance of strategies to increase the participation rate of the services in women 50 years or less, which can help reduce CVD risk. Likewise, interventions to prevent dyslipidemia targeting young premenopausal women should be developed and implemented prior to the menopausal transition.
Peter Chedraui, MD, PhD
Research Professor, School of Postgraduate in Health
Universidad Espíritu Santo, Samborondón, Ecuador
References
- Park J, Son MK, Park HY. Substantial Lipid Increases During Menopausal Transition in Korean Middle-Aged Women. J Korean Med Sci. 2023;38(31):e238.
https://pubmed.ncbi.nlm.nih.gov/37550806/ - Mauvais-Jarvis F, Bairey Merz N, Barnes PJ, et al. Sex and gender: modifiers of health, disease, and medicine. Lancet. 2020;396(10250):565-582.
https://pubmed.ncbi.nlm.nih.gov/32828189/ - Moccia P, Belda-Montesinos R, Monllor-Tormos A, Chedraui P, Cano A. Body weight and fat mass across the menopausal transition: hormonal modulators. Gynecol Endocrinol. 2022;38(2):99-104.
https://pubmed.ncbi.nlm.nih.gov/34898344/ - Stice J, Lee J, Pechenino A, Knowlton A. Estrogen, aging and the cardiovascular system. Future Cardiol. 2009;5(1):93-103.
https://pubmed.ncbi.nlm.nih.gov/19371207/ - Choi Y, Chang Y, Kim BK, Kang D, Kwon MJ, Kim CW, et al. Menopausal stages and serum lipid and lipoprotein abnormalities in middle-aged women. Maturitas. 2015;80(4):399–405.
https://pubmed.ncbi.nlm.nih.gov/25631350/
If you would like to add a comment or contribute to a discussion based on this issue, please contact Menopause Live Editor, Peter Chedraui, at peter.chedraui@cu.ucsg.edu.ec.
