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Title: The effect of oestrogen on the female cardiovascular system
Author: Akkad, Andrea A.
Awarding Body: University of Leicester
Current Institution: University of Leicester
Date of Award: 1999
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The use of postmenopausal oestrogen replacement (HRT) has increased more than threefold over the last two decades. Apart from its effect on menopausal symptoms and-consequently-on quality of life, many women embark on HRT because of its presumed benefits on cardiovascular health. However, some of the effects of oestrogen on the cardiovascular system remain controversial and poorly understood. The present investigation aims to examine the effect of oestrogen on aspects of the female cardiovascular system in vivo and in vitro. In the clinical arm of the study, transdermal oestrogen treatment in oophorectomised women was shown to be associated with an overall reduction in ambulatory blood pressure (ABP), whereas with oral therapy ABP remained unchanged. With both delivery systems, ABP increased significantly in a proportion of women. The reason for this is unclear, however, further investigation did not reveal a demonstrable association with molecular variants of the angiotensinogen genotype. In a pilot study looking at carotid disease in postmenopausal women, oral oestrogen treatment was associated with significant plaque regression, as assessed by ultrasonography. Confirmation in a definitive trial is awaited. In the in vitro arm of the study, a model for the induction of intimal hyperplasia in human ovarian veins was introduced. Intimal thickness increased significantly in culture, and was attenuated by the addition of oestrogen. The underlying mechanisms may be linked to increased VEGF expression in vitro in response to oestrogen, which was also demonstrated in this experiment. When tested in vivo, however, serum VEGF were reduced following exposure to transdermal oestrogen, possibly by reciprocal regulation of VEGF and nitric oxide. In conclusion, postmenopausal oestrogen replacement therapy is associated with demonstrable benefits on blood pressure and vascular disease, and is capable of vascular protection in vitro. Further work is needed to fully investigate underlying mechanisms.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available