Uterine and quality of life changes in postmenopausal women with an asymptomatic tamoxifen-thickened endometrium randomized to continuation of tamoxifen or switching to anastrozole

Objective: Before the knowledge that 5 years of adjuvant tamoxifen is less efficacious than 2 to 3 years of tamoxifen followed by 2 to 3 years of anastrozole/exemestane, we designed a multicenter double-blind randomized controlled trial in women taking tamoxifen with a thickened endometrium to compare uterine and quality-of-life parameters between those switching to anastrozole and those continuing tamoxifen. Methods: Asymptomatic postmenopausal women who took adjuvant tamoxifen for 2 to 3 years for operable breast cancer with a double endometrial thickness greater than 7 mm were randomized to 20 mg tamoxifen or 1 mg anastrozole for the remaining duration, totaling 5 years. Tablets were unrecognizable for drug assignment. The primary endpoints were the differences in double endometrial thickness and uterine volume after 1 year. Uterine and quality-of-life data were analyzed using regression methods, and missing values were handled using multiple imputation. Results: Seventy-two women (median age, 60 y) were randomized in five hospitals. Relative to women continuing tamoxifen, women switching to anastrozole experienced a decrease of 53% (95% CI, 41%-63%) in double endometrial thickness and a decrease of 51% (95% CI, 39%-60%) in uterine volume. Vaginal dryness (b = 0.064; 95% CI, 0.016-0.112) and sexual problems (b = 0.054; 95% CI, 0.007-0.102) increased in women taking anastrozole compared with women taking tamoxifen. Treatment arms did not differ regarding withdrawal rate and the experience of (serious) adverse events. Conclusions: Despite premature trial closure, our data provided valuable insights. Switching to anastrozole strongly decreased the endometrial thickness and uterine volume but increased sexual disturbances. Safe and effective interventions are needed to alleviate sexual dysfunction.