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128 Current Topics in Menopause Marco Stramba-Badiale
prevention strategies [6]. Furthermore, efficacy and safety of cardiovascular
therapy should be evaluated in clinical studies which enroll a significant
proportion of women [7].
EFFECTS OF SEX HORMONES ON THE CARDIOVASCULAR SYSTEM
Cardiac receptors for estrogen, progesterone and androgens have been described
in animals and humans, and their potential functional relevance has been
demonstrated [8, 9]. It has been shown that sex hormones are involved in the
transcription of hormone-sensitive genes such as NO synthases and that they
interfere with various membrane-associated and cytoplasmic signalling pathways
[8-10]. Experimental studies have also suggested that metabolites of estradiol
exert direct effects on vascular cells [11], thus reducing infarct size and improving
cardiac remodelling. Myocardial hypertrophy in female ovariectomized mice with
aortic stenosis is reduced by estrogens administration [12]. It has been shown that
polymorphisms in the gene that encodes the estrogen alpha receptor are associated
with an increased rate of myocardial infarction in men and in women [9] and men
with defects in this receptor develop early atherosclerosis [13].
In women and men, estrogens induce fast vasodilation, improve endothelialmediated
vasodilation, and modulate proliferation or apoptosis of vascular smooth
muscle cells and endothelial cells. Endogenous estrogens also reduce adhesionmolecule
expression and increase the synthesis of vascular endothelial growth
factor, which promotes angiogenesis and stimulates re-endothelialization after
injury [8, 10, 14]. It has been shown that estrogen increases NO synthesis by
increasing the activity of endothelial NO synthase [9].
Finally, endogenous, but not exogenous, estrogen inhibits angiotensinogen
synthesis in the liver and angiotensin AT1 receptor expression in the myocardium,
leading to an increased inhibition of the renin angiotensin system which may
contribute to cardiovascular protection in premenopausal women [9].
On the basis of these observations it is plausible that a reduction in sex hormones
in postmenopausal women might be associated with detrimental effects on the
cardiovascular system.