ABSTRACT
Hormone therapy in postmenopausal women is associated with a decreased risk of developing coronary heart disease (Stampfer and Colditz, 1991); up to 30% of this effect is considered to be due to a beneficial effect on lipid profile. Sex hormones have vasoactive properties which result in direct effects on the vasculature of many systems besides that of the reproductive organs. Estrogen increases cardiac output and decreases systemic vascular resistance in animals and humans. During pregnancy, with its associated changes in circulating sex hormones, there is an increase in cardiac output which has been attributed to substantially increased plasma concentrations of estrogen (Robson et al., 1989). Recently it has been discovered that estrogen relaxes animal and human coronary and cerebral arteries. This may indicate that part of the cardioprotection afforded by hormone therapy is mediated through direct effects on the vascular system, and a number of mechanisms have been proposed to explain this. The present evidence suggests that the mechanisms responsible for acute and chronic effects on blood flow may differ. Recent human studies have investigated the acute direct effects of estrogen on the coronary arteries, implicating roles for direct (vascular smooth muscle) and indirect (endothelium-dependent) mechanisms in estrogen-induced coronary relaxation (Chester et al., 1995; Collins et al., 1994; Reis et al., 1994; Gilligan, Quyyumi and Cannon, 1994; Collins et al., 1995a). However, with long-term therapy other mechanisms may be involved in affecting vascular reactivity such as calcium antagonism and inhibition of atherogenesis (Jiang et al., 1992a; Han et al., 1995; Gruchow et al., 1988; Sullivan et al., 1988; Adams et al., 1990; Wagner et al., 1991). Estrogen has also been shown to affect prostaglandin production (Mendelsohn and Karas, 1994; Mikkola et al., 1995) and responses to vascular constrictor factors like noradrenaline, phenylephrine, 5-hydroxytryptamine and the production of factors like endothelin-1 and angiotensin-II (Shay et al., 1993; Jiang et al., 1992b; Cheng and Gruetter, 1992; Magness, Parker and Rosenfeld, 1993; Brosnihan et al., 1995; Proudler et al., 1995). Some of the beneficial effects of estrogen on the vascular system may be dependent on and independent of the classical estrogen receptor.
