Human Reproduction, Vol. 17, No. 2, 497-502,
February 2002
© 2002 European Society of Human Reproduction and Embryology
Hormone replacement therapy can augment vascular relaxation in post-menopausal women with type 2 diabetes
1 Department of Obstetrics and Gynaecology, University of Glasgow, G3 8SJ, 2 Department of Medicine and Therapeutics, Western Infirmary, University of Glasgow, G11 6NT, 3 Vascular assessment unit, Glasgow Caledonian University, G12 8QQ, 4 Diabetes Centre, Gartnavel General Hospital, North Glasgow Hospitals University NHS Trust, 5 Department of Pathological Biochemistry, University of Glasgow, G31 2ER, 6 Department of Medicine and Therapeutics, Western Infirmary, University of Glasgow, G11 6NT and 7 Department of Obstetrics and Gynaecology, University of Glasgow, Glasgow, UK
BACKGROUND: Diabetes is a major risk factor for coronary heart disease in women and event rates increase substantially after the menopause. Observational studies have suggested that estrogens may provide cardioprotection by regulating endothelial nitric oxide synthase. METHODS: In order to examine the effect of hormone replacement therapy (HRT) on endothelium-dependent and -independent vascular relaxation in post-menopausal women with type 2 diabetes, an open study was conducted in which gluteal biopsies were collected from 17 women before and after 6 months of transdermal 17ß-estradiol (80 µg twice weekly) in combination with oral norethisterone (1 mg daily). Small arteries (<550 µm) were dissected from fat and mounted on a wire myograph for assessment of relaxation in response to acetylcholine (ACh), bradykinin (BK) and sodium nitroprusside (SNP). RESULTS: Maximal relaxation responses to ACh, BK and SNP in women with diabetes and non-diabetic control subjects were 52 ± 8 versus 96 ± 2% (P < 0.05), 76 ± 7 versus 97 ± 1%, (P < 0.05) and 91 ± 2 versus 98 ± 1% (P < 0.05) respectively. After 6 months of HRT, maximal relaxation responses to ACh, BK and SNP in women with diabetes (compared with pre-HRT) were: 88 ± 4 (P < 0.05), 93 ± 3 (P < 0.05) and 98 ± 1% (P < 0.05) respectively. At baseline and after HRT, EC50 (concentration required to obtain 50% of maximum response) data exhibited similar changes. CONCLUSIONS: HRT had potentially beneficial effects on vascular relaxation. Data were consistent with improvements in endothelial function, vascular smooth muscle function, or both. Controlled studies are required to confirm and extend these findings.
Key words: endothelium/hormone replacement therapy/nitric oxide/type 2 diabetes
8 To whom correspondence should be addressed at: Queen Mother's Hospital, Yorkhill, Glasgow, G3 8SJ, UK.E-mail: M.A.Lumsden{at}clinmed.gla.ac.uk
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