Effects of ultralow-dose transdermal estradiol on postmenopausal symptoms in women aged 60 to 80 years

Objective: To investigate the effect of ultralow-dose transdermal estradiol on postmenopausal symptoms and side effects in a cohort of largely asymptomatic postmenopausal women aged 60 to 80 years. Design: This secondary analysis used data from the UltraLow-dose Transdermal estRogen Assessment trial, a randomized, placebo-controlled, double-blind trial in postmenopausal women to determine the skeletal effects and safety of ultralow-dose transdermal estradiol. Four hundred seventeen postmenopausal women, aged 60 to 80 years, were randomly assigned to receive either unopposed transdermal estradiol at 0.014 mg/d (n = 208) or placebo (n = 209). Participants were queried at each clinic visit about postmenopausal symptoms and side effects purported to be associated with estrogen therapy using a standardized questionnaire. Results: At baseline, 16% of women reported hot flashes, 32% reported vaginal dryness, and 35% reported trouble sleeping. Women who received ultralow-dose estradiol were no more likely to report improvement of hot flashes, vaginal dryness, or sleep difficulties than those who received placebo. Treatment with ultralow-dose estradiol did not cause breast tenderness, uterine bleeding, or other symptoms often attributed to estrogen, but vaginal discharge was more common in women who received estradiol compared with those who received placebo. Conclusion: In this population of older, largely asymptomatic women, ultralow-dose transdermal estradiol did not improve postmenopausal symptoms and did not cause side effects other than vaginal discharge. Further study is needed to determine whether this dose of transdermal estradiol is effective in treating symptoms of postmenopause in younger, more symptomatic women.