[Basic principles of hormone replacement therapy in the postmenopause]

17 beta-estradiol, conjugated equine estrogens, esterified estrogens, and estriol constitute postmenopausal replacement therapy, all of which are in clinical use as oral preparations. Non-oral routes--matrix and reservoir patches, gel--were developed for estradiol, as was the intravaginal administration of estriol and estradiol. Daily doses of 1 mg estradiol(valerate) or 25 micrograms estradiol delivered via a patch or 0.5 mg gel or 0.3 mg conjugated equine estrogens are often sufficient to alleviate climacteric symptoms. Bone resorption may be effectively reduced and bone mineral density maintained by 1 mg estradiol or 25 micrograms transdermal estradiol. Maximal bone sparing dosages are 2 mg estradiol, 50 micrograms transdermal estradiol, 0.625 mg conjugated equine estrogens, and 1.25 mg estrone Estriol, predominantly used for the prevention and or treatment of urogenital symptoms, has no bone sparing effect at the doses in clinical use. Non-oral administration of estradiol may be superior in diabetic women and those with hypertriglyceridemia due to the different metabolism which does not mainly involve the hepatic first pass effect. Epidemiological data do not support any preference of oral versus non-oral routes of administration regarding side-effects such as venous thromboembolism. Progestogens--natural progesterone, derivatives structurally related to progesterone and testosterone, respectively--are necessary for endometrial protection. Sequential use of a progestogen for at least 10 days per month, preferably 12-14 days abolishes the increased incidence of endometrial hyperplasia which is likely to develop with unopposed use of estrogen. Observational studies do not suggest any superiority of a given progestogen regarding cardiovascular risk, prevention of osteoporosis, and cognitive function in postmenopausal women on estrogen replacement therapy. Tibolone, a derivative of norethindrone, is yet another option for replacement therapy. The recommended dose for treatment of climacteric symptoms and prevention of bone loss is 2.5 mg. Controlled clinical studies do not suggest that this compound is superior in achieving amenorrhea compared with continuous combined estrogen progestogen replacement therapy, as available data are inconsistent. In early postmenopause the sequential use of a progestogen in conjunction with an estrogen is the preferred treatment option. With advancing postmenopausal age either continuous combined replacement or tibolone may be choices in case withdrawal bleeding is no longer acceptable for women. However, there are no rigid age limit when to change treatments, the selection of which is largely influenced by the preference of the individual's acceptance of withdrawal bleeding.