Estradiol and depression

It has been suggested that the higher rates of depression in women (versus men) are partially hormonal in origin. Walf et al (2008) found that male mice and female mice with artificially elevated levels of 17β-oestradiol (E2) showed a decrease in depressive-type activity. Knockout mice (mice engineered to have no receptors for E2) showed no change in behavior with administration of the hormone. In humans, Epperson et al (2007) found that post-menopausal women treated with E2 were similarly resistant to relapses of depression to women being treated with Prozac. In contrast, Morrison et al (2004) found E2 ineffective in treating current depression in post-menopausal women. E2 levels do not appear to influence depression in men, but testosterone does (according to Barrett-Connor et al, 1999).

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I continue to find it interesting that the relationship between hormones and depression appears to vary by sex: that the same hormone administered to men and women will have different effects on their depressive symptoms. Most of the transmen I know have reported a reduction of depressive-type symptoms after going on testosterone, but most transwomen I know also got less depressed when they started hormones. It's very tempting for me to say that the mood improvement is due to feeling empowered by "doing something" about your transition, but the differential effects in animals and humans make me wonder if it's more complicated than placebo (which is plenty complicated enough).