Effect of hormone therapy on the enteroinsular axis

Menopause is associated with a decline in insulin response to glucose and with insulin resistance. It has been proven that hormone therapy (HT) improves carbohydrate metabolism in postmenopausal women. However, it is known that gastrointestinal hormones play a key role in the coordination of digestion and absorption of ingested nutrients and in the regulation of pancreatic endocrine function. Therefore, the aim of this study was to investigate the effect of HT on gastrointestinal hormones and carbohydrate metabolism in postmenopausal women.

The prospective study was performed in 90 healthy postmenopausal women (mean age 54.5 years, standard deviation 3.34 years), of whom 49 completed the study. They were randomized and treated either with continuous transdermal HT (0.05 mg 17[beta]-estradiol every 24 hours) combined with 5 mg oral dydrogesterone daily (group A, n = 25), or with oral HT (2 mg 17[beta]-estradiol semihydrate every 24 hours) combined with 10 mg dydrogesterone as a continuous therapy (group B, n = 8). The control group (group C, n = 16) received no HT. Both basal and meal-stimulated plasma concentrations of glucose, insulin, glucose-dependent insulinotropic peptide (GIP), glucagon-like peptide-1 (GLP-1), and cholecystokinin (CCK), as well as basal estrogen levels, were measured before HT and after 6 and 12 months of treatment. At the same time intervals, all the studied parameters were measured for group C.

After 12 months of the transdermal HT, a decrease in both fasting (P < 0.002) and postprandial (P < 0.05) plasma glucose levels was observed. Oral HT reduced only the fasting plasma glucose level in the 12th month of treatment (P < 0.05). Regardless of the route of administration, HT reduced postprandial plasma levels of insulin (oral HT: P < 0.05; transdermal HT: P < 0.02). Fasting plasma levels of GIP were reduced after 6 and 12 months of transdermal HT (P < 0.002 and P < 0.001, respectively). Moreover, levels of postprandial GIP were reduced after 6 and 12 months of transdermal HT (P < 0.002 in both cases). Fasting and postprandial GLP-1 levels were reduced by transdermal HT after 12 months of supplementation. Oral HT also decreased these levels, but not significantly. The observed differences may, however, be related not only to the route of administration, but also to the difference in the dose of estradiol. Regardless of the route of administration, HT did not influence plasma levels of CCK.

Hormone therapy significantly influences the enteroinsular axis in postmenopausal women and contributes to the normalization of plasma glucose levels.