Jj. Brennan et al., Serum concentrations of 17 beta-estradiol and estrone after multiple-dose administration of percutaneous estradiol gel in symptomatic menopausal women, THER DRUG M, 23(2), 2001, pp. 134-138
In two multicenter phase III efficacy studies, blood samples were obtained
to evaluate the serum concentrations of 17 beta -estradiol (E2) and unconju
gated estrone (El) after administration of a percutaneous gel or transderma
l patch containing estradiol. In postmenopausal women, normal laboratory E2
and El serum concentrations range from 10-30 pg/mL and 20-40 pg/mL, respec
tively. Study subjects were healthy postmenopausal women with moderate to s
evere hot flushes occurring at least seven times daily or 60 times per week
. Study 1 was a randomized, double-blind, multicenter study of percutaneous
E2 gel 1.25 or 2.5 g (0.75 and 1.5 mg E2, respectively) versus placebo gel
. Study 2 was a double-blind (blinded to E2 gel dose), randomized, active-c
ontrolled, multicenter, 12-week phase 3 study of E2 gel 0.625, 1.25, or 2.5
g (0.375, 0.75, or 1.5 mg E2, respectively) versus a transdermal E2 patch
delivering 0.05 mg E2 per day. Serum E2 and El concentrations were evaluate
d at baseline and at week 12 for study 1 and at baseline and weeks 4, 8, an
d 12 for study 2 using radioimmunoassay. Median serum concentrations of E2
after 1.25- and 2.5-g gel administration appeared to be dose-proportional t
hroughout both studies. In study 1, the median serum concentrations of E2 a
t week 12 were 33.5 and 65.0 pg/mL for 1.25- and 2.5-g gel dose, respective
ly. The corresponding El values were 49.0 and 58.0 pg/mL. In study 2, both
E2 and El concentrations were relatively stable at weeks 4, 8, and 12. E2 v
alues at week 12 for 0.625-, 1.25-, and 2.5-g gel doses and E2 patch were 2
5.0, 32.0, 60.0, and 38.5 pg/mL, respectively. The corresponding El values
were 39.0, 41.0, 62.5, and 40.0 pg/mL. Application of the 1.25-g gel dose a
nd a transdermal patch delivering 50 mug per day of E2 resulted in comparab
le median E2 and El concentrations. However, the 0.625-g gel dose did not p
roduce E2 levels in a range expected to be consistently therapeutic in most
postmenopausal women.