Multiple coronary heart disease risk factors are associated with menopause and influenced by substitutive hormonal therapy in a cohort of French women

doi:10.1016/0021-9150(95)05599-R

Atherosclerosis

Volume 118, Issue 1, November 1995, Pages 123-133

https://doi.org/10.1016/0021-9150(95)05599-R Get rights and content

Abstract

The relationship between menopause and cardiovascular risk factors, and the effect on these risk factors of progestin alone or in combination with estrogen were analysed in a sample of French women. Three thousand four hundred and forty consecutive women, between 45 and 65 years of age, who received a systematic check-up between January 1991 and April 1993 were enrolled in this study. All biological measurements were performed at a central laboratory. Women were classified as premenopausal (n = 1233), postmenopausal (n = 1774) if they had not menstruated in the 12 months before examination, and perimenopausal (n = 433) if they met at least two of the following criteria: elevated levels of serum follicle-stimulating hormone (FSH), irregular menses, amenorrhea for less than 12 months, hot flushes. The effect of menopause on cardiovascular risk factors was determined in 2167 women between 45 and 65 years of age (premenopausal n = 790, postmenopausal n = 1377), none of whom were presently treated with hormonal replacement therapy (HRT). In addition, the effect of progestin was assessed in a group of 397 perimenopausal women, and the effect of combined estrogen and progestin replacement therapy in another group of 1746 postmenopausal women. Menopause was associated with higher levels of serum cholesterol (6.4 vs. 5.9 mmol/l), triglycerides (1.2 vs. 1.0 mmol/l), apolipoprotein (apo) B (1.3 vs. 1.1 g/l), apo A-I (1.9 vs. 1.8 g/l), as well as with elevated diastolic blood pressure (79.7 vs. 77.0 mmHg). Multivariate analysis indicated that these effects were independent of age, body mass index (BMI), glycemia, smoking, alcohol intake, exercise and parity. Perimenopausal women treated with progestin alone (n = 95) were compared to perimenopausal women not using HRT (n = 302). There were no statistically significant differences in the levels of cholesterol, triglycerides, apo B, apo A-I, glycemia and blood pressure between the two groups. Postmenopausal women using a combination of estrogen and progestin (n = 369) had significantly lower levels of serum cholesterol (6.1 vs. 6.4 mmol/l), triglycerides (1.0 vs. 1.2 mmol/l), apo B (1.2 vs. 1.3 g/l), systolic (131.9 vs. 137.9 mmHg) and diastolic (76.9 vs. 79.7 mmHg) blood pressure than postmenopausal women without hormonal therapy (n = 1377), taking into account confounding variables. In contrast, serum apo A-I levels were not altered by the combined hormonal therapy. We conclude that menopause is.

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Fat mass changes during menopause: a metaanalysis
2019, American Journal of Obstetrics and Gynecology
Citation Excerpt :
After the application of inclusion and exclusion criteria, a further 300 publications were excluded (Figure 1). Of the remaining 286 studies, 210 were eligible for inclusion in the quantitative analysis, with 201 studies reporting cross-sectional data15,18-20,35,37-232 and 11 studies reporting longitudinal data.10,38,152,233-240 Some studies included multiple subcohorts of premenopausal and postmenopausal women based on factors such as age,233 ethnicity,45,107 physical activity level,111,213 and geographic location.96,155,167
Data: Fat mass has been shown to increase in aging women; however, the extent to which menopausal status mediates these changes remains unclear. The purpose of this review was to determine (1) how fat mass differs in quantity and distribution between premenopausal and postmenopausal women, (2) whether and how age and/or menopausal status moderates any observed differences, and (3) which type of fat mass measure is best suited to the detection of differences in fat mass between groups.
This review with metaanalyses is reported according to Metaanalysis of Observational Studies in Epidemiology guidelines.
Studies (published up to May 2018) were identified via PubMed to provide fat mass measures in premenopausal and postmenopausal women. We included 201 cross-sectional studies in the metaanalysis, which provided a combined sample size of 1,049,919 individuals and consisted of 478,734 premenopausal women and 571,185 postmenopausal women. Eleven longitudinal studies were included in the metaanalyses, which provided a combined sample size of 2472 women who were premenopausal at baseline and postmenopausal at follow up.
The main findings of this review were that fat mass significantly increased between premenopausal and postmenopausal women across most measures, which included body mass index (1.14 kg/m²; 95% confidence interval, 0.95–1.32 kg/m²), bodyweight (1 kg; 95% confidence interval, 0.44–1.57 kg), body fat percentage (2.88%; 95% confidence interval, 2.13–3.63%), waist circumference (4.63 cm; 95% confidence interval, 3.90–5.35 cm), hip circumference (2.01 cm; 95% confidence interval, 1.36–2.65 cm), waist-hip ratio (0.04; 95% confidence interval, 0.03–0.05), visceral fat (26.90 cm²; 95% confidence interval, 13.12–40.68), and trunk fat percentage (5.49%; 95% confidence interval, 3.91–7.06 cm²). The exception was total leg fat percentage, which significantly decreased (–3.19%; 95% confidence interval, –5.98 to –0.41%). No interactive effects were observed between menopausal status and age across all fat mass measures.
The change in fat mass quantity between premenopausal and postmenopausal women was attributable predominantly to increasing age; menopause had no significant additional influence. However, the decrease in total leg fat percentage and increase in measures of central fat are indicative of a possible change in fat mass distribution after menopause. These changes are likely to, at least in part, be due to hormonal shifts that occur during midlife when women have a higher androgen (ie, testosterone) to estradiol ratio after menopause, which has been linked to enhanced central adiposity deposition. Evidently, these findings suggest attention should be paid to the accumulation of central fat after menopause, whereas increases in total fat mass should be monitored consistently across the lifespan.
The effect of formononetin on the proliferation and migration of human umbilical vein endothelial cells and its mechanism
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The incidence of cardiovascular diseases (CVD) increases in postmenopausal women, suggesting that this condition is related to a low level of estrogen [1,2]. In addition, impaired vascular endothelial function prompts the development of CVD, and experiments revealed that protective action of estrogen on vascular endothelial cells is reduced in postmenopausal women [3–6]. Therefore, it is important to research the mechanism of estrogen in treated vascular endothelial cells.
Formononetin is one of the main active components of traditional Chinese medicine red clover (Trifolium pratense L). Prior studies have demonstrated that formononetin is a typical phytoestrogen and exhibits an estrogen-like effect that protects the cardiovascular system with minimal side effects. In this study, we further investigated the role of formononetin in human umbilical vein endothelial cells (HUVECs) and its potential molecular mechanisms. We founded that formononetin promotes proliferation and migration of HUVECs as assessed by the MTT and wound healing assays. Meanwhile, insulin-like growth factor 1 (IGF-1) and intercellular adhesion molecule 1 (ICAM-1) protein levels were increased in a dose-dependent manner. Our findings illustrated that formononetin exhibits a protective effect on HUVECs, and the molecular mechanisms may correlate with IGF-1R and ICAM-1, as well as upregulation of vascular endothelial growth factor (VEGF) and activation of extracellular signal-regulated kinase (ERK).
Thyroid status in premenopausal and postmenopausal women – A biochemical study on insulin resistance in non obese, overweight and obese type 2 diabetics
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This further proves that strategy based on combinatorial drugs including oral hypoglycemic agents, divalent cations and thyroid receptor modulators/analogs could help in maintaining euthyroid status even in the postmenopausal stage as observed in elderly women with type 2 diabetics. Several groups of workers have shown increased fasting insulin [14,15] and increased fasting glucose levels [16,17] in postmenopausal women compared with premenopausal women, which would imply worsening of insulin resistance with the menopause. However, insulin sensitivity is known to worsen with advancing age and increasing central obesity, making it even more difficult to interpret.
Insulin resistance with altered thyroid status in women is observed in type 2 diabetics and varies with advancing age and estrogen profile. We compared thyroid status between premenopausal and postmenopausal women in obese, non obese and overweight type 2 diabetes.
We included 301type 2 diabetics who were segregated into premenopausal (n = 100) 33.2% and postmenopausal (n = 201) 66.8% among three sub groups (Non obese, overweight and Obese).Anthropometry, fasting blood glucose, lipid profile, glycated hemoglobin, homeostasis model assessment of insulin resistance, liver function tests, Free T4, T3, TSH, Zn²⁺and Mg²⁺ were enabled.
Non obese type 2 diabetics were segregated into two groups n = 21 (29.2%)- premenopausal with mean age of 41.48 ± 4.30 and n = 51 (70.8%) - post menopausal with mean age of 58.49 ± 7.32 There were significant differences in WHR, HbA1c, HDL with p < 0.05 and ALP with p < 0.01; Overweight type 2 diabetics n = 55 (37.9%) -premenopausal with mean age of 41.96 ± 3.80 and n = 90 (62.1%)- post menopausal with mean age of 57.80 ± 7.20. There were significant differences in Urea, Zinc, Total protein, Albumin with p < 0.05 and T4, TSH with p < 0.01. Obese Type 2 diabetics n = 24 (28.6%) -premenopausal with mean age of 42.00 ± 4.30 and n = 60 (71.4%) -post menopausal with mean age of 57.80 ± 7.20. There were significant differences in Urea, Magnesium, Triacylglycerols, and VLDL with p < 0.05, Insulin and HOMA-IR with p < 0.01.
Anthropometry specified classification of type 2 diabetics in pre and postmenopausal women reflects thyroid status.
Effects of menopause, gender and age on lipids and high-density lipoprotein cholesterol subfractions
2015, Maturitas
Citation Excerpt :
Nevertheless, in accord with our observations, analyses of data from large studies of variation in lipid and lipoprotein concentrations with age have consistently shown a greater adverse effect of age on total, LDL and non-HDL cholesterol concentrations in women and a convergence between men and women in the postmenopausal age range [19,24,25]. Analyses that have discriminated an effect of menopause have shown adverse effects of menopause on TC, TG and apoB levels that were independent of age and other confounders, such as BMI, glycaemia, smoking, alcohol intake, exercise and parity [19,22,26]. Studies have compared pre- and postmenopausal women of the same age and shown TC levels to be higher in post- compared with premenopausal women of similar age [2] and, in one study that followed premenopausal women through menopausal transition, a worsening in lipid profile was distinguished as a consequence of menopause, rather than age [15].
To distinguish the effects of menopause, gender and age on serum lipid risk markers for vascular disease, including high-density lipoprotein cholesterol (HDL-C) subfractions 2 and 3 (HDL₂-C and HDL₃-C).
We undertook a cross-sectional database analysis of apparently healthy Caucasian pre- and postmenopausal women and men (n = 515, 518 and 800, respectively) not taking drugs affecting lipid metabolism (including contraceptive or post-menopausal steroids). Measurements of serum total cholesterol (TC), low-density lipoprotein (LDL-C), triglycerides (TG), HDL-C, HDL₂-C, HDL₃-C and non-HDL-C concentrations and the TC/HDL-C concentration ratio were considered.
Men had lower TC than postmenopausal women (p < 0.001) and similar LDL-C. Compared with premenopausal women, postmenopausal women had a more atherogenic lipid profile with lower HDL₂-C (median 0.67 vs 0.60 mmol/L, p < 0.001) but no difference in HDL₃-C (0.96 vs 0.96 mmol/L, p = 0.8). Compared with either pre or postmenopausal women, men had a more atherogenic profile with lower HDL₂-C (0.36 mmol/L) and HDL₃-C (0.91 mmol/L, all p < 0.001). With standardization for confounding variables, including standardization to age of menopause (50 years), differences apparent in the non-standardized comparisons were generally sustained, although HDL₃-C levels were lower at menopause, HDL₂-C ceased to differ and LDL-C was lower in postmenopausal women than men.
Male gender is associated with a more atherogenic profile than female gender, with appreciably lower levels of the HDL₂-C subfraction. Among women, menopause is associated with a more atherogenic lipid profile, but has less effect than male gender.
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The data showing the relation between the menopause status and triglycerides are inconsistent. Many studies have confirmed the relationship between concentrations of TG and the menopausal status, even after adjusting for age, BMI, and other confounding factors [136,147,148]. Other studies have shown no relationship between TG concentration and the menopausal status or have found that an increase in TG with menopause was mainly explained by the chronological aging of women [78,130].
Menopause is a risk factor for cardiometabolic diseases, including metabolic syndrome (MetS), type 2 diabetes, and cardiovascular diseases. MetS is a constellation of interdependent factors such as insulin resistance, abdominal obesity, dyslipidemia, and hypertension. The prevalence of MetS in postmenopause is due to loss of the protective role of estrogens and increased circulating androgens resulting in changes to body fat distribution and development of abdominal obesity. Excessive visceral adipose tissue plays an important role due to synthesis and secretion of bioactive substances such as adipocytokines, proinflammatory cytokines, reactive oxygen species, prothrombotic, and vasoconstrictor factors. MetS may also impact risk assessment of breast cancer, osteoporosis and chronic kidney disease, and quality of life during the menopausal transition. Increased MetS has stimulated the exploration of new laboratory tests for early detection and therapies.
Estrogen: A master regulator of bioenergetic systems in the brain and body
2014, Frontiers in Neuroendocrinology
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Susceptibility to developing insulin resistance is known to increase with age (Carr, 2003; Iozzo et al., 1999), but there is less evidence that sex differentially affects development of insulin resistance. Fasting insulin (Poehlman et al., 1995; Razay et al., 2007) and glucose (Dallongeville et al., 1995; Lynch et al., 2002) levels have been shown to rise as estrogen levels decrease during the menopausal transition, but this is proposed as a secondary response to the change in body fat distribution and not a direct effect of estrogen decline (Wing et al., 1992, 1991). One study suggests women may have differential insulin metabolism after menopause, with postmenopausal women producing less insulin, but eliminating it more slowly (Walton et al., 1993).
Estrogen is a fundamental regulator of the metabolic system of the female brain and body. Within the brain, estrogen regulates glucose transport, aerobic glycolysis, and mitochondrial function to generate ATP. In the body, estrogen protects against adiposity, insulin resistance, and type II diabetes, and regulates energy intake and expenditure. During menopause, decline in circulating estrogen is coincident with decline in brain bioenergetics and shift towards a metabolically compromised phenotype. Compensatory bioenergetic adaptations, or lack thereof, to estrogen loss could determine risk of late-onset Alzheimer’s disease. Estrogen coordinates brain and body metabolism, such that peripheral metabolic state can indicate bioenergetic status of the brain. By generating biomarker profiles that encompass peripheral metabolic changes occurring with menopause, individual risk profiles for decreased brain bioenergetics and cognitive decline can be created. Biomarker profiles could identify women at risk while also serving as indicators of efficacy of hormone therapy or other preventative interventions.

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Research reportMultiple coronary heart disease risk factors are associated with menopause and influenced by substitutive hormonal therapy in a cohort of French women

Abstract

J Lipid Res

Atherosclerosis

Maturitas

J Chron Dis

Atherosclerosis

Prev Med

Prev Med

Am J Obstet Gynecol

Maturitas

J Biol Chem

Maturitas

Maturitas

The epidemiology of cardiovascular disease in postmenopausal women

Ann NY Acad Sci

Menopause and coronary heart disease: The Framingham Study

Ann Int Med

Increased risk of atherosclerosis in women after the menopause

Br Med J

Plasma lipid, lipoprotein cholesterol and apoprotein distributions in selected US communities

Arterioscler Thromb

Factors associated with low and elevated plasma high density lipoprotein cholesterol and apolipoprotein A-I levels in the Framingham Offspring Study

J Lipid Res

Research report
Multiple coronary heart disease risk factors are associated with menopause and influenced by substitutive hormonal therapy in a cohort of French women