Effects of tibolone and cyclic hormone replacement therapy on glucose metabolism in non-diabetic obese postmenopausal women: a randomized study

Department of Obstetrics and Gynecology, University Hospital of Oulu, FIN-90014 University of Oulu, Oulu, Finland.

OBJECTIVE AND METHODS: To study the effects of hormone replacement therapy on glucose metabolism, 31 obese (body mass index > or =27 kg/m(2)) postmenopausal women were randomized to treatment with tibolone (2.5 mg once daily; TIB; n=16) or to oestradiol valerate (2 mg daily)-dydrogesterone (20 mg daily for 2 weeks every 3 months; ED; n=15) for 12 months. Oral (OGTTs) and intravenous glucose tolerance tests (IVGTTs) and a euglycaemic hyperinsulinaemic clamp were performed before and at 6 and 12 months of treatment. RESULTS: TIB decreased the rates of whole body glucose uptake (WBGU) at 6 (P=0.04) and 12 months (P<0.001), but it did not have a significant effect on glucose tolerance. In OGTTs, serum insulin and C-peptide concentrations 2 h after the oral glucose load were increased (P<0.001 and P=0.05 respectively) at 12 months of treatment with TIB, but no changes in the areas under the curve (AUC) of insulin or C-peptide were observed. Furthermore, TIB did not have a significant effect on insulin secretion, the metabolic clearance rate (MCR) of insulin or hepatic insulin extraction. Treatment with ED did not modify the rates of WBGU, but it increased the MCR of insulin (P=0.017) and hepatic insulin extraction (P<0.001) and tended to decrease the insulin AUC (P=0.07). Moreover, glucose tolerance slightly deteriorated during this treatment (P=0.02). Although early phase insulin secretion evaluated by the serum C-peptide response at 30 min in the OGTT increased (P=0.046), the first-phase insulin response during the IVGTT decreased (P=0.05) during ED treatment. CONCLUSIONS: Despite the impairment in peripheral insulin sensitivity, TIB treatment had a neutral effect on glucose tolerance, possibly due to a compensatory decrease in endogenous glucose production. The increased demand on insulin induced by ED, due to both a stimulatory effect on pancreatic beta cells and increased insulin metabolism, may explain the slightly detrimental effect on glucose tolerance with this treatment.

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