Effects of tibolone and conjugated equine estrogens with or without medroxyprogesterone acetate on body composition and fasting carbohydrate measures in surgically postmenopausal monkeys

Abstract

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.