Effect of hormone replacement therapy on inflammation-sensitive proteins in post-menopausal women with Type 2 diabetes.

AIMS: To test the effect of oral hormone replacement therapy (HRT) on plasma C-reactive protein (CRP), soluble vascular cell adhesion molecule-1 (VCAM-1), soluble intercellular adhesion molecule-1 (ICAM-1) and IL-6 concentrations and leucocyte count in post-menopausal women with Type 2 diabetes. METHODS: Post-menopausal women with Type 2 diabetes (n = 61) were randomized in a double-blind fashion to receive either continuous combined hormone replacement therapy (n = 29) with conjugated equine oestrogen (0.625 mg/day) plus medroxyprogesterone acetate (2.5 mg/day) or placebo (n = 32) for 6 months. Study variables were measured at baseline and at the end of the study. RESULTS: Eight women randomized to hormone replacement therapy and four women assigned to placebo group dropped out of the study. Plasma CRP increased (2.2 mg/l, 95% confidence interval 0.3-4.1 mg/l) significantly (P = 0.02) in women treated with HRT (n = 21) compared with placebo (n = 29) taking baseline CRP, body mass index (BMI) and smoking status into account. Plasma levels of cell adhesion molecules, IL-6 and leucocyte count did not change significantly during the study. CONCLUSIONS: These findings indicate that oral HRT with conjugated equine oestrogen plus medroxyprogesterone acetate increases plasma CRP levels but not necessarily global inflammatory activity in post-menopausal diabetic women. An increase in plasma CRP may potentially increase risk of a cardiovascular event.

Hormone-replacement therapy increases serum paraoxonase arylesterase activity in diabetic postmenopausal women.

The paraoxonase (PON1) enzyme is associated with high-density lipoproteins (HDL) in the blood and is low in patients with type 2 diabetes. Hormone-replacement therapy (HRT) can increase HDL cholesterol levels, but its effect on serum PON1 arylesterase activity is uncertain. The aim of the present study was to determine the effect of 6 months' HRT with conjugated equine estrogen and medroxyprogesterone acetate on serum PON1 arylesterase activity in postmenopausal women with type 2 diabetes. Serum PON1 activity was measured immediately before and at the end of the second arm of a randomized, placebo-controlled, crossover with washout study originally designed to test the effect of HRT on plasma lipids in diabetic postmenopausal women. Baseline serum PON1 arylesterase activity was significantly (P <.001) lower in the postmenopausal diabetic women (149 +/- 38 micromol/mL/min; n = 47) than values in healthy postmenopausal women (173 +/- 32 micromol/mL/min; n = 51). Serum PON1 activity increased (10%) significantly (P =.009) in diabetic women treated with HRT compared with placebo. A significant (P =.02) interaction between baseline PON1 activity and treatment indicated a greater increase in PON1 activity during HRT in women with lower baseline activities. At baseline, serum PON1 arylesterase activity was correlated significantly with plasma HDL cholesterol levels in diabetic women (r = 0.333, P =.01, n = 47), and the increase in serum PON1 activity was correlated significantly with the change in plasma HDL cholesterol during HRT (r = 0.659, P =.0001, n = 28). These data suggest that serum PON1 activity is abnormally low in postmenopausal women with type 2 diabetes and increases during HRT, particularly in women with lower baseline levels and in those who show a concomitant increase in HDL cholesterol.