Short-term effects of low-dose estrogen/drospirenone vs low-dose estrogen/dydrogesterone on glycemic fluctuations in postmenopausal women with metabolic syndrome

This study aims to compare the effects of low-dose emidrate estradiol/drospirenone (E2/DRSP) vs low-dose emidrate estradiol/dydrogesterone (E2/DG) combination on the mean amplitude of glycemic excursions (MAGE) value in postmenopausal women affected by metabolic syndrome (MS). One hundred sixty postmenopausal women were recruited to receive a treatment with oral doses of E2/1 mg plus drospirenone/2 mg (E2/DRSP group) or oral dose of E2/1 mg plus dydrogesterone/5 mg (E2/DG group) for 6 months. At enrollment and after 6 months, anthropometric, metabolic, and inflammatory parameters have been assessed. MAGE, evaluated during 48-h continuous subcutaneous glucose monitoring (CSGM), allowed us to assess daily glucose fluctuations at baseline and after 6 months. After hormone therapy, both groups showed a significant decline in fasting plasma glucose levels (p < 0.05), while only E2/DRSP group showed a statistically significant decline in waist circumferences, post-prandial glycemia, LDL, plasma triglycerides, MAGE, HOMA index, and plasma IL-6 (p < 0.05) levels. In the whole population (n = 160), after 6 months of indicated therapy, changes in fasting plasma glucose and PAI-1 levels correlated with the changes in MAGE values, while only in E2/DRSP group that MAGE reduction was positively associated with a stronger decrease in waist circumferences, triglycerides, and TNF-α plasma levels. The independent effect of hormone therapy (HT) on reduction in MAGE value has been tested in three different multiple linear regression models. HT resulted to be associated with MAGE, independent of other confounding variables. Although both groups had a decline in fasting plasma glucose, only drospirenone treatment revealed positive effects on glycemic excursions and insulin sensitivity, induced favorable changes in lipid profile, and showed an improvement of inflammatory indices in postmenopausal women with MS.