c-peptide and tibolone

To determine the effects of tibolone or oestradiol (E(2) )/norethisterone acetate (NETA) hormone replacement therapy on glucose and insulin metabolism in postmenopausal women.. Single-centre double-blind placebo-controlled randomized clinical trial.. We randomized 105 healthy postmenopausal women to tibolone 2·5 mg daily, continuous combined oral E(2) 2 mg/NETA 1 mg daily or placebo over a 2-year study. We performed intravenous glucose tolerance tests (IVGTT) with measurements of plasma glucose, insulin and C-peptide concentrations and the IVGTT glucose elimination rate, k. Mathematical modelling was performed to determine measures of insulin sensitivity, S(i) , pancreatic insulin secretion and hepatic and plasma insulin elimination.. Tibolone decreased S(i) to 53-63% and k to 72-79% of baseline values but increased IVGTT phase 2 C-peptide concentrations 1·6-1·8-fold and pancreatic insulin secretion 2·2-2·4-fold, so overall IVGTT glucose concentrations were unaffected. Similar, but for k, significantly smaller changes in insulin and C-peptide secretion were seen with E(2) /NETA, also with no effect on overall IVGTT glucose concentrations.. Tibolone reduces insulin sensitivity. Healthy postmenopausal women seem able to compensate for this and maintain normal postload glucose concentrations, but it may not be advisable to prescribe tibolone to women with, or at increased risk for, diabetes.

Topics: Aged; Blood Glucose; C-Peptide; Contraceptives, Oral, Synthetic; Estradiol; Estrogen Receptor Modulators; Estrogens; Female; Glucose; Humans; Insulin; Insulin Resistance; Middle Aged; Norethindrone; Norpregnenes

Hormone treatment (HT) after the menopause affects lipid and carbohydrate metabolism and inflammation and may modify risk factors relevant for the clinical expression of the metabolic syndrome and cardiovascular disease. Tibolone has pharmacodynamic properties different from other hormone preparations. Here, we compare the effect of combined HT and tibolone on metabolic risk markers for the development of cardiovascular disease.. Postmenopausal women were randomly assigned to 1.25 or 2.5 mg/day of tibolone or oral continuous combined conjugated equine estrogen plus medroxyprogesterone acetate (CEE/MPA). Cardiovascular risk factors were determined at baseline and after 12 months of treatment.. Body mass index and blood pressure were unaffected by the HT. HOMA-IR decreased in the CEE/MPA group (3.69 vs. 3.38; p = 0.02). Treatment with tibolone increased tissue-type plasminogen activator activity (0.87 IU/ml vs. 1.21 IU/ml; p = 0.005) and C-reactive protein (0.83 mg/l vs. 1.88 mg/l; p < 0.001), and decreased plasminogen activator inhibitor activity (6.9 IU/ml vs. 2.0 IU/ml; p < 0.001) and triglycerides (0.99 vs. 0.87 mmol/l; p = 0.004). Both treatments decreased total cholesterol significantly.. CEE/MPA and tibolone have comparable effects on most metabolic risk factors investigated. The effect of tibolone on fibrinolysis and triglycerides suggests that tibolone has a favorable pharmacological profile on these risk factors when compared to CEE/MPA.

Topics: Blood Pressure; Body Composition; C-Peptide; Cardiovascular Diseases; Drug Therapy, Combination; Estrogen Receptor Modulators; Estrogens, Conjugated (USP); Female; Fibrinolysis; Humans; Medroxyprogesterone Acetate; Metabolic Syndrome; Middle Aged; Norpregnenes; Tissue Plasminogen Activator; Treatment Outcome; Triglycerides

To investigate the effects of tibolone on carbohydrate metabolism, and to compare these effects with those of a sequential regimen of conjugated equine estrogens and medrogestone.. This was an open-label, multicentre, comparative study. Seventy-two postmenopausal women were randomized to receive either tibolone 2.5 mg/day or conjugated equine estrogens 0.6 mg plus sequential medrogestone 5 mg (CEE/M) for six 28-day cycles. Carbohydrate metabolism was evaluated at baseline and after three and six cycles of treatment by an oral glucose tolerance test (OGTT). A blood sample was taken at 30, 60, 90 and 120 mm after glucose 75 mg dosing for determination of plasma glucose, insulin and connecting peptide (C-peptide) levels.. The changes from baseline of glucose, insulin and C-peptide area-under-the-curve (AUC) values were not statistically significant after 3 and 6 months of tibolone or CEE/M treatment. There was a small transitory decrease in HbA(1C) after three cycles of treatment with tibolone.. The effects of tibolone and CEE/M on carbohydrate metabolism were considered to have no clinical significance.

Topics: Blood Glucose; C-Peptide; Drug Administration Schedule; Estrogen Receptor Modulators; Estrogens, Conjugated (USP); Female; Glucose Tolerance Test; Hormone Replacement Therapy; Humans; Insulin; Medrogestone; Middle Aged; Netherlands; Norpregnenes; Postmenopause

The effects of tibolone on body weight, body composition, and fasting carbohydrate measures in surgically postmenopausal cynomolgus monkeys were compared to those of conjugated equine estrogens (CEE) with and without medroxyprogesterone acetate (MPA). Monkeys were fed a moderately atherogenic diet with either no hormones (control n = 29), CEE (0.042 mg/kg, n = 27), CEE + MPA (0.167 mg/kg, n = 29), low-dose tibolone (LoTib, 0.05 mg/kg, n = 30), or high-dose tibolone (HiTib, 0.20 mg/kg, n = 31) daily for 2 years. Body weight (BW) was measured throughout the study, and dual-energy x-ray absorptiometry (DEXA) scans of the abdominal region (lumbar vertebrae 1 through 5) were performed at the end of the trial to assess abdominal body composition. Fasting carbohydrate measures (glucose, insulin, C-peptide, and fructosamine) were determined at baseline and after 2 years of treatment. Compared to controls, BW significantly increased and abdominal soft tissue mass was greater (analysis of variance [ANOVA], P <.001, P = 0.003, respectively) in all but the CEE-treated group (P =.78, P =.94, respectively). HiTib-treated monkeys had greater abdominal lean mass compared to controls (P =.008), while there was no significant treatment effect on abdominal fat mass (analysis of covariance [ANCOVA], P =.29). Fasting insulin concentrations and fasting insulin/glucose ratios were greater in CEE + MPA- (P =.002, P =.03, respectively) and HiTib-treated monkeys (P =.03, P =.02, respectively) compared to controls. There was a strong trend for a treatment effect on fasting blood glucose concentration (ANCOVA, P =.06) with CEE + MPA-treated animals having the greatest values, despite no difference in fructosamine concentration (ANCOVA, P =.57). Using these fasting measures, the homeostasis model assessment (HOMA-IR) revealed significant insulin resistance with CEE + MPA treatment compared to controls (P =.008), while the quantitative insulin sensitivity check index (QUICKI) showed significantly impaired insulin sensitivity in all hormone replacement therapy (HRT) groups (all P values <.03), except CEE (P =.12). In conclusion, HRT with CEE + MPA or tibolone results in greater BW, abdominal soft tissue, and insulin resistance (CEE + MPA and HiTib) compared to control-treated monkeys.

Topics: Animals; Arteriosclerosis; Blood Glucose; Body Composition; Body Weight; C-Peptide; Carbohydrates; Dietary Fats; Energy Intake; Estrogen Replacement Therapy; Estrogens, Conjugated (USP); Fasting; Female; Fructosamine; Insulin; Insulin Resistance; Macaca fascicularis; Medroxyprogesterone Acetate; Norpregnenes; Ovariectomy; Postmenopause