Summary
The risk of cardiovascular disease (CVD) is higher in the postmenopausal period. The effect that the type of menopause, natural versus surgical, or the age at natural onset of menopause has on CVD needs further investigation. This prompted Price et al. [1] to study of the association between the type and timing of menopause and the 10-year office based Framingham Risk Score (FRS) in women (45 to 85 years) from the Canadian Longitudinal Study on Aging. Women included were menopausal at time of recruitment and had no prior CVD. As main covariates, the authors examined age, education, province of residency, and the use of hormone therapy. A total of 10,090 women (8,200 natural menopausal and 1,890 surgical menopausal) were eligible for the study. Surgical menopause was associated with a higher mean FRS compared with natural menopause (CVD risk 12.4% vs 10.8%, p<0.001). Compared to women with an age at natural menopause from 50 to 54 years (CVD risk 10.2%), natural menopause before age 40, 40 to 44, or 45 to 49 years had a higher CVD risk (12.2%, 11.4%, and 10.6%, respectively, p<0.001). The author conclude that their study supports an association between the type of menopause and its timing over CVD risk prediction and highlights the need to be judicious about surgical menopause.
Commentary
CVD is the global leading cause of women’s mortality. Certain menopausal characteristics, type of menopause, and natural menopausal timing have been associated with CVD risk. The present commented study found that surgical menopause was associated with a higher CVD risk when compared with natural menopause [1]. In a cohort study that included 144,260 postmenopausal women [2], premature menopause (PM), compared with no PM, was significantly associated with increased risk for a composite outcome that included coronary artery disease, heart failure, aortic stenosis, mitral regurgitation, atrial fibrillation, ischemic stroke, peripheral artery disease, and venous thromboembolism. For natural PM, the hazard ratio was 1.36 and for surgical PM, the hazard ratio was 1.87, meaning that natural and surgical PM may be associated with higher risk for CVD. Natural and surgical PM (before age 40 years) were associated with a small but statistically significant increased risk for a composite of CVD among postmenopausal women [2]. An Argentinean interhospital network study found that 5.96% of women with premature ovarian insufficiency (POF) resulted from gynecological surgeries due to benign pathologies; highlighting the importance of a conservative approach in gynecological surgery [3]. CVD risk increases with earlier menopause, whether natural or surgical, but surgical menopause has been associated with an additional risk. It should be noted that hormone therapy HT in cases of surgical menopause reduced but did not eliminate the excess CVD risk [4].
The age at menopause is inversely related to the risk of coronary heart disease (CHD). Surgical menopause is associated with an increased risk of CHD, regardless of the age at menopause. For each year of decreased age at menopause results in a 2% increased risk of incident CHD [5]. Estrogens affect elasticity of blood vessels and regulates the level of metabolic mediators such as lipids, inflammatory markers and coagulation factors. They also have a protective effect on CVD by stimulating endothelial nitric oxide synthase, which mediates vasodilation and maintains cardiovascular health, hence playing an important role in maintaining and improving cardiovascular health. Hormonal status can be used to assess populations with poor cardiovascular health for targeted interventions [6]. We agree with the authors [1], that preventative interventions for CVD should be considered in surgical menopausal women and women with an age at natural menopause less than 45 years.
Sandra C. Demayo, MD
Past President of the Argentinian Society of Gynecological and Reproductive Endocrinology (SAEGRE), Chair of the Gynecological Endocrinology Area, Argerich Hospital, Buenos Aires, Argentina, Fellow of the American College of Obstetricians and Gynecologists
Prof. Blanca Campostrini, MD, PhD
General Secretary of the Argentinian Society of Gynecological and Reproductive Endocrinology (SAEGRE), Past-President of the Argentine Association for Climacteric Studies (AAPEC), Fellow of the American College of Obstetricians and Gynecologists
References
- Price MA, Alvarado BE, Rosendaal NTA, Câmara SMA, Pirkle CM, Velez MP. Early and surgical menopause associated with higher Framingham Risk Scores for cardiovascular disease in the Canadian Longitudinal Study on Aging. Menopause. 2021;28(5):484-490.
https://pubmed.ncbi.nlm.nih.gov/33399323/ - Honigberg MC, Zekavat SM, Aragam K, et al. Association of Premature Natural and Surgical Menopause With Incident Cardiovascular Disease. JAMA. 2019;322(24):2411-2421.
https://pubmed.ncbi.nlm.nih.gov/31738818/ - Demayo S, Giannone L, Monastero A, et al. Reality of premature ovarian failure in Argentina. Rev Assoc Med Bras (1992). 2019;65(3):419-423.
https://pubmed.ncbi.nlm.nih.gov/30994842/ - Zhu D, Chung HF, Dobson AJ, et al. Type of menopause, age of menopause and variations in the risk of incident cardiovascular disease: pooled analysis of individual data from 10 international studies. Hum Reprod. 2020;35(8):1933-1943.
https://pubmed.ncbi.nlm.nih.gov/32563191/ - Dam V, van der Schouw YT, Onland-Moret NC, et al. Association of menopausal characteristics and risk of coronary heart disease: a pan-European case-cohort analysis. Int J Epidemiol. 2019;48(4):1275-1285.
https://pubmed.ncbi.nlm.nih.gov/30796459/ - Chen L, Hu Z, Wang X, et al. Age at Menarche and Menopause, Reproductive Lifespan, and Risk of Cardiovascular Events Among Chinese Postmenopausal Women: Results From a Large National Representative Cohort Study. Front Cardiovasc Med. 2022;9:870360.
https://pubmed.ncbi.nlm.nih.gov/36158833/
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