Lenzetto, delivering a dose of 1.53mg estradiol per metered dose, is licensed as HRT for oestrogen deficiency symptoms in postmenopausal women with or without a uterus at least six months after last menses or surgical menopause.
The initial recommended dose is one metered-dose spray to the forearm once daily for four weeks, after which the dose may be increased to two sprays once daily if required. In women with a uterus a progestogen should be added for 12—14 days of each cycle. The need for continued treatment should be reassessed every three to six months.
In a small pharmacokinetic study, 72 healthy postmenopausal women were randomly assigned to receive one, two or three sprays of estradiol metered-dose transdermal spray (1.53mg per spray) once daily for 14 days.
The estradiol spray was shown to deliver estradiol at therapeutic levels with serum levels peaking quickly at 18 to 20 hours post-dose. Steady-state trough serum concentrations of estradiol were reached after 7 to 8 days in all dose groups.
Estradiol spray was also shown to produce low serum estrone and estrone sulfate concentrations with estrone/estradiol ratios comparable to those observed in premenopausal women.
The safety and efficacy of estradiol metered-dose transdermal spray (1.53mg per spray) were assessed in a double-blind, parallel-group study involving 454 postmenopausal women experiencing at least eight moderate to severe hot flushes per day. Women were randomised to one of six treatment groups: one, two or three estradiol sprays or matching placebo spray once daily.
A stastistically significant reduction in the frequency of moderate to severe hot flushes was observed for all three estradiol groups at weeks 4 and 12 compared with the placebo groups (p<0.010). By week 4, the difference in flush frequency between estradiol and placebo exceeded two per day in all dose groups, a difference that was maintained or increased in subsequent weeks.
Estradiol spray was well tolerated in the study with a similar rate of treatment-related application site reactions reported in the treatment and placebo groups (1.3% versus 1.8%, respectively).
Skin-to-skin transfer minimal
In an 18-day study involving 20 healthy postmenopausal women, use of a transdermal estradiol spray did not result in a significant transfer of estradiol to men who came into direct contact with the application site.
The same study showed that estradiol absorption was not significantly affected by washing the application site 1 hour after dosing with the study drug but was slightly decreased by the application of sunscreen 1 hour after dosing. However, application of sunscreen 1 hour before dosing had no significant effect on estradiol absorption.