Hormone therapy impairs endothelial function in postmenopausal women with type 2 diabetes mellitus treated with rosiglitazone.
Diabetes and ovarian senescence are associated with impaired endothelial function and altered arterial mechanical properties. Alterations in normal vascular structure and functioning are the primary cause of mortality and morbidity with type 2 diabetes. Similarly, after menopause, women experience an increase in the rate of cardiovascular disease. Thiazolidinediones have exhibited a number of antiatherogenic actions in populations with type 2 diabetes. The effect of thiazolidinediones in combination with hormone therapy (HT) in postmenopausal women is, however, unknown. To assess whether HT (transdermal estradiol 50 microg and micronized progesterone (100 mg/d) affects vascular function, 21 women receiving rosiglitazone were randomly assigned to receive HT or placebo for 12 wk in a double-blind crossover design. Measures of glycemic control, lipids, blood pressure, flow-mediated dilation, and distensibility index were undertaken at baseline and after each treatment. As a result, flow-mediated dilation was significantly reduced (15.3 +/- 3.8 to 6.6 +/- 1.6%, P = 0.02) with HT, whereas lipids, blood pressure, and distensibility index were unchanged. Placebo had no significant affect on any variables. Thus, the addition of HT to rosiglitazone treatment attenuates endothelial function without altering other cardiovascular risk factors. Caution should, therefore, be exercised when considering combined treatment with thiazolidinedione and HT.
Honisett
Suzy Y
SY
Department of Medicine, Monash University, The Alfred Hospital, Commercial Road, Prahran, Victoria, Australia 3181.
Stojanovska
Lily
L
Sudhir
Krishnankutty
K
Kingwell
Bronwyn A
BA
Dawood
Tye
T
Komesaroff
Paul A
PA
D000368:Aged; D001794:Blood Pressure; D003327:Coronary Disease / Q000209:etiology; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D004958:Estradiol / Q000008:administration & dosage*; D005260:Female; D020249:Hormone Replacement Therapy / Q000009:adverse effects*; D006801:Humans; D008055:Lipids / Q000097:blood; D008875:Middle Aged; D017698:Postmenopause; D011374:Progesterone / Q000008:administration & dosage*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000627:therapeutic use*; D014157:Transcription Factors / Q000378:metabolism
D008055:Lipids; D018160:Receptors, Cytoplasmic and Nuclear; D045162:Thiazolidinediones; D014157:Transcription Factors; D000077154:Rosiglitazone; D011374:Progesterone; D004958:Estradiol