| The prevalence of type 2 diabetes mellitus (T2DM) is 5 to 10% in western countries, while a large percentage of patients remains undiagnosed [1]. Menopause represents the end of reproductive life of women and is associated with metabolic changes which predispose to T2DM. One of the most prevalent phenotypical changes noted after menopause is weight gain. The decrease in estrogen concentrations leads to an increase in total body fat, specifically central abdominal fat accumulation. The abdominal obesity results in additional physical and psychological morbidity, initiating a vicious cycle. Excessive energy intake, sedentary lifestyle and stress are environmental factors that are often present during menopause and further contribute in the development of central obesity [2]. In turn, abdominal fat deposition leads to low grade inflammation and insulin resistance, through the action of cytokines and adipokines. Pancreatic β-cells have then to compensate insulin resistance in order to maintain normal glucose levels. Ultimately, only a subgroup of women with central obesity in menopause will demonstrate impaired glucose metabolism and T2DM. The genetic predisposition of β-cell dysfunction seems to constitute a crucial parameter [3]. Interestingly, women with climacteric symptoms present greater risk for development of diabetes [4]. Various animal and human studies have provided evidence that hormone replacement treatment (HRT) can ameliorate the tendency towards central obesity after menopause, with improvement of insulin sensitivity and reduction of the risk for T2DM. In large randomized controlled trials, T2DM incidence was decreased from 12% to 21% in women on HRT, with significant improvement of central adiposity, insulin resistance, lipids levels and inflammation markers [5]. However, HRT cannot be provided forever and there is not enough evidence to support administration of HRT for T2DM prevention [4,6]. Clearly, more research data are required in order to identify those women most likely to gain metabolic benefits from HRT. Diabetes is broadly considered to be a cardiovascular disease equivalent, which would suggest that women with the disease should not take HRT. However, women with established T2DM show better glycemic control and demand lower doses of antidiabetic agents when on HRT. Unfortunately, clinical trials so far were not powered enough to assess differences in cardiovascular outcomes. It seems that HRT is beneficial in early menopause for women with T2DM, while in older women with mature atherosclerotic plaques this kind of therapy may destabilize them, resulting in acute thrombotic episodes. An individualized approach in treating menopausal symptoms should be considered with a low threshold to recommend non-hormonal therapies, particularly in women with concurrent cardiovascular disease. Some women with T2DM may be excellent candidates for HRT, following careful evaluation of their cardiovascular risk [2,6]. |