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Relationship between Serum Estradiol Levels and the Increases in High-Density Lipoprotein Levels in Postmenopausal Women Treated with Oral Estradiol¹

Departments of Obstetrics and Gynecology (B.M.W.) and Medicine (F.M.S.), Brigham and Women’s Hospital, and the Departments of Nutrition (F.M.S.), Epidemiology (D.S., M.M.), and Biostatistics (D.S., M.M.), Harvard School of Public Health, Boston, Massachusetts 02115

Address all correspondence and requests for reprints to: Brian M. Walsh, Department of Obstetrics and Gynecology, Brigham and Women’s Hospital, 75 Francis Street, Boston, Massachusetts 02115. E-mail: bwwalsh{at}bics.bwh.harvard.edu

Postmenopausal women are prescribed a standard dose of estrogen, which is optimal 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 treatments in random order for 9 weeks each: a) placebo, b) 1 mg oral estradiol daily, and c) 2 mg oral estradiol daily. Lipoprotein and estradiol (E₂) levels were measured 10–12 h after pills were taken. E₂ levels with 1 mg estradiol were positively correlated with the increases in HDL levels (r = 0.70, P < 0.01). Only the eight subjects who had E₂ levels < 50 pg/mL after 1 mg estradiol treatment demonstrated further increases in HDL levels by increasing 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 E₂ 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, measurement of an E₂ level the morning after taking 1 mg estradiol at bedtime identifies who may benefit from improvement in HDL levels by increasing to a 2-mg dose.

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