A double-blind comparative study of Estraderm and Premarin in the amelioration of postmenopausal symptoms.

Patients whose postmenopausal symptoms were being satisfactorily controlled with conjugated equine estrogens, either 0.625 mg/day (n = 57) or 1.25 mg/day (n = 67), participated in a study that compared the efficacy of these oral regimens with that of 17 beta-estradiol, 0.1 mg/day, administered through intact skin. The study was a multicenter, double-blind, randomized, parallel-group trial during which two thirds of the patients who received each dosage of conjugated equine estrogens were changed to an estradiol transdermal system while the remainder continued with conjugated equine estrogens. A total of 124 patients was included in the analysis of efficacy. The analysis revealed no significant differences between the estradiol transdermal system and conjugated equine estrogens in control of hot flushes or other postmenopausal symptoms and no statistically significant differences between treatment groups in regard to estrogen-related side effects. Minor topical reactions to the transdermal systems were reported during only about 20% of study weeks. Thus, transdermal estradiol, 0.1 mg/day, appears to be equally effective as conjugated equine estrogens, 0.625 or 1.25 mg/day, for controlling postmenopausal symptoms and is well tolerated.

Pharmacokinetics and pharmacodynamics of transdermal dosage forms of 17 beta-estradiol: comparison with conventional oral estrogens used for hormone replacement.

This open-label, multiple-crossover study compared the pharmacokinetics and pharmacodynamics of transdermal 17 beta-estradiol and two oral forms of estrogen replacement therapy in postmenopausal women. The transdermal systems delivered either 0.025, 0.05, or 0.1 mg/day; oral dosages were 2 mg of micronized 17 beta-estradiol or 1.25 mg of conjugated equine estrogens. Transdermal estradiol provided serum and urinary levels of estradiol conjugates typical of the early follicular phase of the premenopausal woman and an estradiol/estrone ratio that approximated 1. The increments of both serum and urinary estradiol showed dose proportionality. Serum levels of estradiol obtained 24 hours after oral administration of estrogens were in a range similar to the steady-state levels obtained with transdermal estradiol delivery. Oral estrogens, however, induced an excessive rise in estrone to levels far beyond those observed in premenopausal women. Continuous application of transdermal estradiol over 3 weeks did not result in any accumulation of estradiol or estradiol conjugates. After only three doses of oral estrogens, there were signs of retention of estrogens. Suppression of gonadotropins by oral and transdermal administration of estrogens was in a similar range. This observation supports the conclusions that levels of circulating estradiol are relevant to efficacy, and that excessively high levels of estrone after oral administration of estrogens merely represents a nonphysiologic precursor or metabolite pattern.