Relationship between serum estradiol levels and the increases in high-density lipoprotein levels in postmenopausal women treated with oral estradiol

Postmenopausal women are prescribed a standard dose of estrogen, which is o ptimal for a population but not for all individuals. We wished to identify if an individual's estradiol level can indicate the minimum effective dose of estrogen which maximally increases high-density lipoprotein (HDL) levels , which could be cardioprotective. We performed a prospective, double-blind crossover study in 19 healthy postmenopausal women, receiving three treatm ents in random order for 9 weeks each a) placebo, b) 1 mg oral estradiol da ily, and c) 2 mg oral estradiol daily. Lipoprotein and estradiol (E-2) leve ls were measured 10-12 h after pills were taken. E-2 levels with 1 mg estra diol were positively correlated with the increases in HDL levels (r = 0.70, P < 0.01). Only the eight subjects who had E-2 levels < 50 pg/mL after 1 m g estradiol treatment demonstrated further increases in HDL levels by incre asing the daily dose to 2 mg (by 3 +/- 5% with 1 mg estradiol and by 13 +/- 7% with 2 mg). The other 11 subjects who had E-2 levels > 50 pg/mL with 1 mg estradiol had no additional benefit from increasing the estradiol dose ( HDL increased by 13 +/- 9% with 1 mg, and by 17 +/- 10% with 2 mg). Thus, m easurement of an E-2 level the morning after taking 1 mg estradiol at bedti me identifies who may benefit from improvement in HDL levels by increasing to a 2-mg dose.