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 micrograms/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. Dose-response 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 micrograms/24 h dosage and higher. A significant negative correlation (r = 0.6045; P less than 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.

Effect of transdermal l7?-estradiol and oral conjugated equine estrogens on biochemical parameters of bone resorption in natural menopause

“…The serum levels of E2 attained in the TTS group were significantly lower (41 pg/ml), but nonetheless induced a similar inhibition in bone resorption. They are consistent with previous studies, which report circulating levels of E2 of 39 pg/ml [26], 33 pg/ml [27], or 38 pg/ml [28] in similar conditions. Our findings confirm a previous report showing that transdermal ERT prevented bone loss with circulating concentrations of E2 remaining below 40 and 50 pg/ml [7].…”

Perimenopause: The Complex Endocrinology of the Menopausal Transition

“…However, this study did find (without showing the primary data) that VMS "inversely correlated to the decrease in E 2 around the menopause" (141). These observations do not negate the efficacy of estrogen therapy for VMS (142,143). However, they do indicate that the relationships between estrogen levels and VMS are more complex than directly inverse with low estrogen levels.…”

Efficacy of Every-Other-Day Administration of Conjugated Equine Estrogen and Medroxyprogesterone Acetate on Gonadotropin-Releasing Hormone Agonists Treatment in Women with Endometriosis

“…In our previous study in postmenopausal women, the mean serum levels of 17ß-estradiol treated with 0.625 mg CEE plus 2.5 mg MPA every day and every other day after 12 months of treatment were 22.5 and 14.9 pg/ml, respectively, with the serum levels of 17ß-estradiol required to relieve vasomotor symptoms and increase bone mineral density being about 15 pg/ml, which causes fewer instances of breakthrough bleeding [6]. Excessive levels of estradiol may result in marked side effects and complications [20]. In this study, the serum level of 17ß-estradiol in the add-back group after 6 months of treatment was about 17 pg/ml, and this level may be quite suitable for Irahara/Uemura/Yasui/Kinoshita/Yamada/ Tezuka/Kiyokawa/Kamada/Aono inducing regression in endometriotic lesions and preventing side effects induced by chronic hypoestrogenism.…”