17 beta-estradiol for postmenopausal estrogen replacement therapy

After physiological or surgical menopause, women are suddenly deficient in their main estrogenic hormone, 17 beta-estradiol. Only a very small amount of estradiol is still produced from adrenal precursors. More than 50 per cent of all postmenopausal women suffer for varying periods of time from the symptoms of this estrogen deficiency, most notably vasomotor instability (hot flashes) and sleep disturbances. The trophic symptoms of estrogen deficiency have longer lasting and cumulative consequences: accelerated loss of bone density that eventually increases the risk of fractures, genitourinary atrophy resulting in dyspareunia and urinary atrophy; and lipoprotein changes with increased risk of coronary heart morbidity and mortality. Today estrogen deficiency is mainly treated by oral estrogens--either conjugated equine estrogens or estradiol--in milligram doses far in excess of what would be required by the parenteral route. Taken orally, estradiol is largely transformed to estrone through metabolism in the liver. Certain undesirable side effects of estrogen therapy (e.g., increased renin substrate) are caused by the unphysiologic nature of the oral route of administration. Dosage forms for parenteral estrogen administration have been widely studied: vaginal or percutaneous creams, intranasal solutions, and sublingual tablets. All of these result in a pronounced, transient elevation of plasma concentrations of estradiol and a minor increase of estrone. An improved regimen, which produces more constant plasma concentrations, is achieved with an experimental estradiol implant or with a vaginal ring delivering estradiol. These studies demonstrate that daily estradiol doses of 0.2 mg and less are effective in reducing hot flashes. Effective doses of conjugated estrogens and estradiol administered by different routes achieve estradiol plasma concentrations of similar magnitude (between 35 and 100 pg/ml). Estrone plasma levels vary widely with these different regimens and do not seem to be directly related to efficacy. In summary, the literature indicates that efficacy of estrogen replacement for the treatment of the menopausal symptoms appears to relate to the magnitude of estradiol plasma levels; effective therapy is achieved by an estradiol regimen that maintains plasma estradiol levels of at least 35-55 pg/ml. Efficacy of estrogens in the prevention of osteoporosis as assessed by densitometry has been demonstrated for conjugated oral estrogens.(ABSTRACT TRUNCATED AT 400 WORDS)