Menopausal hormone therapy in women with dyslipidemia and nonalcoholic fatty liver disease

Abstract

The cessation of ovarian function is associated with an increase in abdominal adipose tissue, dyslipidemia, and nonalcoholic fatty liver disease (NAFLD), which may contribute to the augmented cardiovascular risk observed in postmenopausal women. After ovarian function stops, circulating triglyceride, total cholesterol, and low-density lipoprotein-cholesterol (LDL-C) concentrations increase, whereas high-density lipoprotein-cholesterol (HDL-C) and lipoprotein (Lp(a)) remain essentially unchanged. Similarly, the rates of NAFLD, possibly including the advanced forms of the disease (e.g., hepatic fibrosis), increase in postmenopausal compared with premenopausal women. These effects make menopausal hormone therapy (MHT) an attractive way to restore them. Estrogen per os decreases LDL-C and Lp(a) and increases HDL-C and triglyceride concentrations. The transdermal administration of estrogen has a more neutral effect on triglycerides, albeit a less beneficial effect on LDL-C, HDL-C, and Lp(a). Co-administration of a progestagen diminishes the effect of estrogen on LDL-C, HDL-C, and Lp(a), which, however, remains beneficial. Importantly, the effect may vary with different progestagens, being lesser with natural progesterone and dydrogesterone. Regarding the effect of MHT on NAFLD, though experimental data are currently favorable, clinical evidence is to date limited and controversial. Therefore, there is a need for specifically designed clinical trials, ideally with paired liver biopsies, to demonstrate the effect of different MHT schemes on NAFLD, which is of considerable importance, given that NAFLD is more prevalent after the cessation of ovarian function.

Keywords: Cardiovascular disease; Dyslipidemia; Hormone replacement therapy; Insulin resistance; Menopausal hormone therapy; Nonalcoholic fatty liver disease; Nonalcoholic steatohepatitis; Obesity.