A systematic review including 26 studies was abstracted in DARE. The average number of patients in the studies was 47 (range 10 to 110). 14 studies assigned pariticipants to treatment or control groups through random assignment. Estrogen significantly reduced depressed mood (effect size = 0.69). Studies that compared estrogen treatment with estrogen plus progesterone treatment yielded a mean effect size of 0.62, indicating that the addition of progesterone to the estrogen reduced the effect of HRT on depressed mood.
Another systematic review evaluating the effectiveness of treatments included 108 trials assessing psychological symptoms and 125 trials assessing quality of life. Compared with placebo, estrogen was effective for depressive symtoms: standardized effect size was -0.36 (95% CI -0.53 to -0.20; 18 trials, n=2 104) and for anxiety symptoms: standardized effect size was -0.34 (95% CI -0.50 to -0.18; 13 trials, n=1 718). The pairwise psychological outcome standardized mean differences for depression symptoms were -0.43 (-0.60 to -0.26) for SSRI/SNRI; -0.41 (-0.57 to -0.25) for high estrogen; -0.31 (-0.48 to -0.15) for standard estrogen, and -0.12 (-0.42 to 0.18) for low estrogen. Compared with placebo, for quality of life the stardardized effect size for standard dose estrogen was 0.55 (95% CI 0.41 to 0.69; 26 trials, n=31 263) and for high dose estrogen 0.76 (95% CI 0.48 to 1.03; 5 trials, n=789).