The role of progestins in hormone replacement therapy.

Long-term estrogen replacement therapy prevents osteoporosis and reduces the risk of cardiovascular disease in postmenopausal women. Progestins are used to prevent endometrial hyperplasia and carcinoma but should not be prescribed for women who have had hysterectomies. Doses that decrease mitotic activity are sufficient. Recent data suggest that a continuous combined regimen of estrogen and progestin may increase bone mass in women who have established osteoporosis. Some progestins may oppose the beneficial effects of estrogen on the cardiovascular system in some women. Critical cardiovascular effects of progestins include a reduction in the serum level of high-density lipoprotein cholesterol and a direct effect on arterial tone, which may be mediated by an attenuation of prostacyclin production and other factors. Therefore it is prudent to prescribe the lowest effective dose of a progestin that demonstrates the least metabolic impact. The dose and type of progestin should be balanced with the estrogen component so that the estrogen-dominant metabolic effects prevail. With this approach the difference in mortality rates between women who use unopposed estrogen and women who use estrogen-progestin therapy will be minimized and will make the appropriate sequential addition of progestin an option in postmenopausal hormone replacement therapy.