• endothelin;
  • type 2 diabetes;
  • metabolic syndrome;
  • postmenopausal;
  • hormonal replacement therapy;
  • angiotensin convertase enzyme inhibitors


Aim  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 μg/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.