Plasma endothelin in postmenopausal women with type 2 diabetes mellitus and metabolic syndrome: a comparison of oral combined and transdermal oestrogen-only replacement therapy.
OBJECTIVE
Type 2 diabetes and metabolic syndrome are major cardiovascular risk factors in postmenopausal women, but the role of vasoconstrictive endothelin-1 (ET-1) in these conditions is not known. We studied the levels of ET-1 and the effect of postmenopausal hormonal therapy on ET-1 levels in postmenopausal women.


METHODS
We compared plasma levels of ET-1 in 22 postmenopausal type 2 diabetic women and 14 postmenopausal women with metabolic syndrome with plasma levels in 10 healthy postmenopausal control women. The basal values for ET-1 were measured for all groups. These women were then randomised to receive in a double-dummy, crossover trial: either oral continuous oestradiol (2.0 mg) + norethisterone acetate (1.0 mg) per day or continuous transdermal oestrogen-only (50 mg/day) for 3 months. Between the active therapy there were 3-month wash-out periods. ET-1-values were measured again at the end of each treatment period.


RESULTS
The type 2 diabetic women had significantly (p < 0.003) elevated ET-1 levels (4.8+/-1.0 pg/ml) whereas those with metabolic syndrome (4.4+/-1.7 pg/ml]) had non-significantly (NS) elevated ET-1 levels compared to controls (3.6+/-0.3 pg/ml). Both oral and transdermal hormone replacement therapy (HRT) failed to affect plasma ET-1 except in 14 hypertensive women from the diabetes and metabolic syndrome groups who were on angiotensin convertase enzyme (ACE) inhibitors. These women's ET-1 levels before oral HRT (4.6+/-1.1 pg/ml) fell to 4.1+/-0.9 pg/ml (p < 0.05).


CONCLUSIONS
Type 2 diabetes in postmenopausal women is associated with elevated ET-1 levels. Oestrogen replacement therapy does not affect the levels of ET-1 in postmenopausal women with type 2 diabetes or metabolic syndrome.
Department of Medicine, Central Hospital of Middle Finland, Jyväskylä. juha.saltevo@ksshp.fi
J
J
Saltevo
J
J
Puolakka
O
O
Ylikorkala
D000279:Administration, Cutaneous; D000284:Administration, Oral; D015415:Biomarkers / Q000097:blood; D001824:Body Constitution; D015992:Body Mass Index; D008076:Cholesterol, HDL / Q000097:blood; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000503:physiopathology*; D019332:Endothelin-1 / Q000097:blood*; D004958:Estradiol / Q000008:administration & dosage; D015914:Estrogen Replacement Therapy; D005260:Female; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood / Q000503:physiopathology*; D006973:Hypertension / Q000097:blood / Q000503:physiopathology*; D008875:Middle Aged; D009640:Norethindrone / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077563:Norethindrone Acetate; D017698:Postmenopause; D012016:Reference Values; D013577:Syndrome; D014280:Triglycerides / Q000097:blood
D015415:Biomarkers; D008076:Cholesterol, HDL; D019332:Endothelin-1; D014280:Triglycerides; D004958:Estradiol; D000077563:Norethindrone Acetate; D009640:Norethindrone