The perimenopausal period is one of the most important stages in the female life cycle.

Physical and mental  symptoms are common in this stage due to the metabolic disturbance of hormones.

Mood changes make women seek medical care during the menopausal transition and over a third of women with depression experience their first episode of depression during the perimenopausal period.

Among women attending community or university menopause clinics, two-thirds of those at a London site and three-quarters of those at a San Diego site met criteria for recurrent major depression (beginning prior to perimenopause) when evaluated by a psychiatric interview.
Transition to menopause and its changing hormonal milieu are strongly associated with new onset of low mood among
women with no history of depression.

An association between estrogen activity and mood disturbance in women has been well established.

The effect of estrogen on mood is partly mediated by the hypothalamus.

Changes in estrogen levels have been found to affect the levels of dopamine and serotonin, which are both important mood-stabilizing neurotransmitters.

Estrogen affects the serotonin system through increasing the rate of degradation of monoamine oxidase.

Sudden estrogen withdrawal, fluctuating estrogen, and sustained estrogen deficit may induce mood disorders, including depression, in estrogen-sensitive women.

The serotonindeficit hypothesis is the most prominent biological theory of the etiology of depression.

Estrogen has been found to stimulate a significant increase of the density of 5-hydroxytryptamine 3A binding sites in the areas of the brain concerned with the control of mood, mental state, cognition, emotion, and behavior.

Estrogen was also found to modulate serotonergic function and thus mood.