ERβ agonist alters RNA splicing factor expression and has a longer window of antidepressant effectiveness than estradiol after long-term ovariectomy.

These findings suggest that ERβ alternative splicing and altered responses in the regulatory system for serotonin may mediate the antidepressant efficacy of ET associated with the timing of therapy initiation. It is likely that ERβ-specific ligands would be effective estrogen-based antidepressants late after the onset of menopause.