18 January 2021
Summary
Sriprasert et al. [1] performed a post hoc analysis of a United States multicenter randomized clinical trial (REPLENISH trial) in order to identify the association between the dose of estradiol (E2) and serum E2 levels and metabolic parameters among early (<6 years; n=1,216) as compared to late (≥10 years, n=297) postmenopausal women. To this end, four doses of TX-001HR (a new oral formulation of combined E2 and progesterone [P4]) were tested against placebo. Linear mixed-effects models adjusted for P4 levels were used to verify the associations between E2 (dose and serum levels) and changes in the levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), and glucose measured at six visits over 12 months.
They found that higher E2 doses and serum E2 levels were significantly related to lower TC and LDL-C and higher HDL-C levels in early but not in late postmenopausal women. These associations weakened with longer time since menopause onset. Higher E2 serum levels were also associated with lower fasting glucose and higher TG levels in early postmenopausal women. The authors concluded that the dose of E2 differentially affects metabolic measures among early compared with late postmenopausal women, supporting the timing hypothesis of the benefits of E2 therapy on cardiovascular disease risk.
Commentary
During the menopausal transition, due to a decline in ovarian function and estrogen secretion, women are subject to bio-psycho and social changes that can impair their quality of life. More importantly, after menopause, cardiovascular risk increases significantly, partly due to estrogen deprivation. Moreover, an increase in weight and other factors (i.e sedentary lifestyle, dietary habits, etc) negatively impact metabolic parameters, making women more susceptible to cardiovascular events. Various studies suggest that estrogens have positive effects on female lipid profile and vasculature due to their antioxidant effect [2], gene modulation expression [3] and regulation of the inflammatory pathway [4]. Despite this evidence, women and professionals are still reluctant to use menopausal hormone treatment (MHT), especially when cardiovascular risk factors such as obesity, hypertension, diabetes, and smoking, are present. Although cardiovascular disease is the leading cause of death in women after menopause, many require MHT, especially those who are symptomatic and in the early postmenopausal stage.
