Objective: The objective of this study was to evaluate the efficacy and safety of three doses of estradiol gel 0.1% (Divigel, a novel formulation consisting of 1 mg estradiol per 1 g transdermal gel) to reduce the frequency and severity of vasomotor symptoms and signs of vulvar and vaginal atrophy associated with menopause.
Design: A total of 488 postmenopausal women were evaluated in a 12-week study comparing placebo with estradiol gel 0.1% at doses of 1.0, 0.5, and 0.25 mg/day, with estimated daily deliveries of 0.027, 0.009, and 0.003 mg of estradiol, respectively. Primary endpoints were the change from baseline in daily frequency and severity of moderate to severe vasomotor symptoms. Change from baseline in the signs of vulvar and vaginal atrophy (vaginal pH and percentage of superficial cells) was also assessed.
Results: Treatment with estradiol gel 0.1% showed statistically significant reductions in frequency and severity of vasomotor symptoms from baseline compared with placebo as early as Week 2 that were maintained throughout treatment. Signs of vulvar and vaginal atrophy were also significantly improved from baseline with all three doses of estradiol gel 0.1% compared with placebo.
Conclusions: Low-dose transdermal estradiol gel 0.1% is an effective treatment for relief of vasomotor symptoms, as well as signs of vulvar and vaginal atrophy, associated with menopause. Estradiol gel 0.1% offers multiple dosing options to individualize patient therapy, including the lowest available effective dose (0.25 mg estradiol, delivering 0.003 mg/d estradiol) to treat the vasomotor symptoms of menopause.