The signs and symptoms of genitourinary syndrome of menopause (GSM) may include loss of vaginal rugae, decrease of superficial cells, increase of parabasal cells, increase in vaginal pH, and dyspareunia. Imvexxy® (estradiol vaginal inserts) (TherapeuticsMD) is a low dose (4-μg and 10-μg) 17β-estradiol softgel vaginal insert FDA approved for the treatment of moderate to severe dyspareunia, a symptom of vulvar and vaginal atrophy, due to menopause. Basic science research has shown that vaginal epithelial estradiol receptors have a reciprocal relationship with estradiol blood test values: the higher the density of receptors, the lower the values. Hypothetically, a low dose (4 μg, 10 μg) of intravaginal estradiol, while not increasing estradiol blood values, should act on the highest density of vaginal epithelial estradiol receptors. A 12-week, double-blind, placebo-controlled phase 3 trial (REJOICE) of the three doses of vaginal estradiol (TX-004HR) was designed, testing the clinical response of Imvexxy® in women who met inclusion and exclusion criteria. The objective of this specific analysis was to determine the rate of early responders at week 2 and how that response might predict responders at week 12.