Effects of sex steroids on serum lipids and lipoproteins

Cardiovascular disease is the leading cause of death in women but manifests itself primarily in the postmenopausal years. Menopause appears to increase the cardiovascular risk, at least when surgically induced, whereas the effects of the natural menopause are still a matter of debate. Why postmenopausal women apparently lose their natural cardioprotection is not established, but oestrogen deficiency seems to play an important role. Loss of ovarian hormone production at the menopause significantly alters serum lipids and lipoproteins, giving rise to more atherogenic lipid profiles throughout the postmenopausal years, and these changes may in part be responsible for the alleged cardiovascular risk. Postmenopausal hormone replacement therapy, using oral unopposed oestrogens, induces potential favourable effects on lipids and lipoproteins, and epidemiological evidence has established that the risk of cardiovascular mortality is reduced by 40-60% in women receiving postmenopausal oestrogen therapy. Part of this reduction seems to be explained by changes in lipids and lipoproteins. Parenteral administration of oestrogens induces comparable, although less pronounced effects on lipids and lipoproteins, and the possible cardioprotective role of parenteral administration remains obscure. The addition of progestogens to postmenopausal oestrogen therapy is essential for endometrial protection, but progestogens apparently antagonize some of the actions of oestrogens on lipid metabolism. However, the type, the dose, the duration and the route of administration, as well as the potency balance between the oestrogen and the progestogen employed, are important determinants for the ultimate effect on lipid metabolism. With the use of cyclic administration and the lowest possible doses of progestogens, the oestrogenic actions on lipids and lipoproteins can be largely preserved, but the cardioprotective potential of combined oestrogen-progestogen therapy is as yet unknown.