Menopause, central body fatness, and insulin resistance: effects of hormone-replacement therapy.

ABSTRACT

In addition to being associated with termination of reproductive life in women, the menopause coincides with an increase in several comorbidities including cardiovascular disease. This increase in the prevalence of cardiovascular disease in the postmenopausal years has been partially attributed to adverse effects of estrogen deficiency on plasma lipid-lipoprotein levels and on the cardiovascular system, although other factors are contributing. Central body fatness and insulin resistance are components of a cluster of metabolic abnormalities which also increases the risk of cardiovascular disease. This review summarizes studies that have examined the effects of the menopause transition and of estrogen-replacement therapy on central body fatness and insulin resistance. Review of cross-sectional studies suggests that the menopause transition is associated with an increase in abdominal and visceral adipose tissue accumulation, as measured either with dual X-ray absorptiometry or computed tomography. These results appear to be independent of the aging process and total body fatness. In general, cross-sectional studies using circumference measurements did not find any significant effect of the menopause. Longitudinal studies also support that accumulation of central body fatness accelerates with menopause. The effects of the menopause on insulin resistance appear to be moderate, if any, although available studies are clearly insufficient to draw firm conclusions. The majority of interventional studies support the notion that hormone-replacement therapy attenuates the accumulation of central fat in postmenopausal women, compared with control or placebo-treated women. Retrospective comparisons of hormone users and nonusers also support a protective effect of hormone replacement on fat distribution. Moderate effects of estrogen therapy were found on insulin resistance in postmenopausal women, although long-term, controlled trials using accurate measurements of insulin sensitivity are lacking. Treatment with progestins exerts moderate deleterious effects on insulin sensitivity, which may be attributable to the partial androgenicity of progestins used. It is concluded that part of the increased incidence of cardiovascular disease in postmenopausal women may be attributable to increased central body fatness. Therapies aiming at preventing these changes in fat distribution such as hormone-replacement therapy, diet or exercise are likely to provide long-term cardiovascular and metabolic benefits for women's health.