Treatment of Hot Flashes with Transdermal Estradiol Administration*

Abstract

A randomized prospective double blind study was performed to assess the ability of a transdermal therapeutic system (TTS) delivering estradiol (E₂) to suppress hot flashes (HFs) in symptomatic postmenopausal women. Patients were given placebo or E₂ in four doses for a 20-day period, and serum gonadotropin and estrogen levels and the occurrences of HFs were measured. Administration of placebo had no measurable effect on either estrogen or gonadotropin levels or the occurrence of HFs. A dose-response relationship was found between the rate of E2 administered and the circulating level of E₂, with 25, 50, 100, and 200 μ/24 h dosages raising the mean E2 concentrations from mean baseline levels of 5-8 pg/ml to 18, 38, 73, and 100 pg/ml, respectively. Estrone levels also increased with TTS application, but to a lesser extent than did E₂ levels. Doseresponse reductions of FSH and LH with increasing amounts of E₂ administration occurred, but gonadotropin levels were not lowered in any of the patients into the ranges found in premenopausal women. TTS application significantly suppressed the occurrence of HFs at the 50 Mg/24 h dosage and higher. A significant negative correlation (r = 0.6045; P < 0.001) between E₂ levels and the rates of occurrence of HFs was found during hormone administration. Based on this regression, 50% and 100% reductions of HFs should occur at 61 and 122 pg/ml E₂. These data indicate that the transdermal delivery of E₂ with these systems significantly reduced the occurrence of HFs and allowed definition of the therapeutic range of hormone replacement in terms of lost ovarian function, as reflected by circulating E₂ levels.