Changes in hormonal environment probably do not alone cause depressive symptoms, but act in concert with genetic and psychosocial factors.
Higher rates of depression may be due to hormonal factors, or to the presence of mood disorders (ie PMDD, PPD) specific to women during reproductive years.
Estrogen has been shown to increase density of 5-HT2A receptors in the brain. Low estrogen is thought to be associated with reduced activity of the serotonin system.
A number of twin studies found that there were no significant differences between men and women in heritability of depression.
One study found by positron emission tomography that serotonin synthesis is 52% higher in male brains compared to female brains.
Hypothyroidism is associated with severe depression, and women are affected by thyroid diseases up to 10 times more frequently than men. Depression may be attributed to subclinical hypothyroidism in some women. Reduced thyroid function is associated with reduced 5HT activity; thyroid replacement increases 5HT activity and reduces depressive symptoms.
Some studies have shown that biological changes during menopause do not significantly affect depression, although mild mood changes may be present. However, the presence of "life stress" has a strong influence on development of depressive symptoms and the experience of menopause varies across individuals and cultures, so some women may be prone to experiencing depression during menopause .