The Concept of CMR
Intra-abdominal Adipose Tissue: the Culprit?
Influence of Menopause
- Abdominal (visceral) adiposity increases with the onset of menopause.
- Abdominal tissue redistribution with menopause appears to be independent of age and total body fat and could be related to a relative deficit in estrogens.
- Menopause has a negative impact on plasma lipoprotein-lipid levels, which may increase CVD risk.
- HTR in post-menopausal women helps protect against intra-abdominal fat accumulation. However, prospective studies that have assessed “hard” CVD endpoints have failed to confirm HRT’s benefits. Current evidence does not support the use of HRT to reduce menopause-related CVD risk.
The Influence of Menopause on Adipose Tissue Distribution
The physiological changes associated with menopause have a significant impact on total body fat and adipose tissue distribution. Because intra-abdominal adipose tissue deposition in women is also influenced by age, it is important to consider this variable when discussing the influence of menopause on adipose tissue distribution.
Several cross-sectional studies have reported a significant difference in body mass index (BMI)—a crude marker of obesity—between pre-menopausal and post-menopausal women that was no longer significant after adjusting for age (1, 2). However, other studies have found that menopause has a significant effect on BMI independent of age (3-5). Some studies that have used dual energy X-ray absorptiometry (DEXA) to measure total body fat more precisely have found that menopause has no significant effect on total body fat (4, 6), whereas other groups have reported that post-menopausal women were heavier than pre-menopausal women after adjusting for age (7, 8).
The central accumulation of body fat with menopause, as assessed by anthropometric measurements or imaging techniques, is a well described phenomenon. Several cross-sectional studies that have used waist-to-hip ratio or waist circumference as estimates of relative or absolute accumulation of abdominal fat respectively have failed to link abdominal adipose tissue accumulation and menopause (2-4, 9-11). Even after controlling for age or BMI, no association between menopause and abdominal obesity has been found (3, 11, 12). However, by using DEXA to measure abdominal adipose tissue (trunkal fat), several investigators have noted that menopause has an independent effect on adipose tissue distribution even after controlling for age (8, 13) and BMI (1, 6) .
It is the use of precise imaging techniques to measure subcutaneous vs. intra-abdominal (visceral) adipose tissue depots that has conclusively shown that menopause has an independent effect on adipose tissue distribution even after correcting for age (14) and BMI (12). In this regard, Kotani et al. (14) reported that intra-abdominal adipose tissue accumulates twice as fast in post-menopausal women as it does in pre-menopausal women. Other studies have also demonstrated that the ratio of abdominal subcutaneous to intra-abdominal adipose tissue was lower in post-menopausal women than in pre-menopausal women (15). Moreover, Toth et al. (16) noted that fat mass was 35% higher while intra-abdominal adipose tissue accumulation was 57% greater in post-menopausal women than in pre-menopausal women, lending further weight to the notion that adipose tissue accumulates selectively in the abdominal cavity with menopause. Figure 1 shows the increased accumulation of intra-abdominal adipose tissue distribution in post-menopausal women even without significant changes in BMI values when compared to pre-menopausal women (17).
Although cross-sectional studies provide relevant information on the “effect” of menopause on adipose tissue distribution, only longitudinal studies can provide a clear picture of the changes that occur in women going through menopause.
Unfortunately, only a few longitudinal studies have examined this issue. Several studies have reported increases in total body fat mass with age (18-20). In a six-year longitudinal study, Björkelund et al. (19) found that abdominal adipose tissue accumulated selectively in women who became post-menopausal when compared to women who remained pre-menopausal over the same period. Changes in adipose tissue distribution were observed using anthropometric measurements such as waist-to-hip ratio and waist circumference. In addition, BMI remained similar between post-menopausal and pre-menopausal women. Further longitudinal studies that use more accurate intra-abdominal fat measurement methods—such as magnetic resonance imaging or computed tomography—are needed to better describe the effect of menopause transition on body fat distribution.
As mentioned above, post-menopausal women are characterized by increased intra-abdominal adipose tissue accumulation when compared to pre-menopausal women. There is evidence that hormone replacement therapy (HRT), which is typically used for alleviating symptoms of menopause, can also limit intra-abdominal adipose tissue accumulation. HRT has been shown to modify abdominal fat distribution by reducing intra-abdominal adipose tissue in estrogen-supplemented post-menopausal women, as compared to controls receiving a placebo (10, 21). In fact, the administration of estrogens and progestins has been found to enhance lipoprotein lipase activity and lipid accumulation in the femoral region but not in the abdominal area (22). These results are consistent with the notion that sex steroids may play a major role in controlling regional adipose tissue accumulation.
Further studies are needed to better document the independent effect of menopause on intra-abdominal adipose tissue deposition. A key focus of these studies must be precise measurement of intra-abdominal adipose tissue.
Metabolic Consequences of Adipose Tissue Redistribution After Menopause
As mentioned above, women generally accumulate more intra-abdominal adipose tissue as they go through menopause. It is unclear whether menopause is a cardiovascular risk factor for all women or only for those with the android pattern of adipose tissue distribution. However, it is well established that increasing intra-abdominal adipose tissue is one of the most prevalent manifestations of a cluster of abnormalities referred to as the metabolic syndrome, which predicts an increased cardiovascular disease risk (23). Some atherogenic metabolic changes associated with menopause are illustrated in Figure 2.
There is some debate about whether menopause increases the risk of cardiovascular disease independent of normal ageing (2, 24, 25). However, postmenopausal women have higher total cholesterol, increased LDL cholesterol and triglyceride as well as lower HDL (increased HDL3 and decreased HDL2) cholesterol levels than pre-menopausal women (26, 27). High levels of HDL2 cholesterol appear to be responsible for the cardioprotective effect of HDL cholesterol. Substantial changes in LDL concentrations occur early in the transition from pre-menopause to post-menopause (28). The proportion of small, dense LDL particles also increases in women during this period (29). Menopause is therefore associated with the development of an atherogenic lipoprotein-lipid profile, which may raise coronary heart disease risk in post-menopausal women.
A few studies have examined the effect of menopause on insulin resistance. Several groups have shown that fasting insulin (2, 30) and glucose concentrations (30, 31) were higher in post-menopausal women than in pre-menopausal women. Toth et al. (16) found that the post-menopausal status per se was not associated with decreased insulin sensitivity, as assessed by the hyperinsulinemic-euglycemic clamp. Matthews et al. (24) also reported that menopause did not affect plasma glucose, insulin levels, body weight, and blood pressure. However, more work is clearly needed here to clarify the true impact of menopause on glucose-insulin homeostasis.
The reduction in intra-abdominal adipose tissue deposition observed with hormone replacement therapy in post-menopausal women is associated with a corresponding improvement in fasting lipid levels (except for triglycerides) (21). Several studies have noted a reduction in LDL cholesterol and a rise in HDL cholesterol levels following hormone replacement therapy (24, 32, 33). Accordingly, estrogen supplementation may be associated with a cardioprotective metabolic profile, although studies that have assessed “hard” cardiovascular (CVD) endpoints have failed to confirm this notion. This issue remains hotly debated in the literature.
In conclusion, the above observations support the notion that hormonally-induced redistribution of adipose tissue in the intra-abdominal (visceral) depots in post-menopausal women leads to adverse changes in the metabolic profile. Further research will enhance understanding of the influence of estrogens and hormone replacement therapy on fat tissue distribution and CVD risk factors.
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