The physical changes that lead up to menopause can take women's bodies by storm. What women heading into menopause may not know is that in addition to some of the better known symptoms of this change, they are at increased risk for depression. A new study helps explain why.

Perimenopause is the time period during which the female body is shifting from fertility and monthly menstrual cycles to infertility and the absence of periods. During this transition, periods become irregular — women experience both shorter and longer, heavier and lighter cycles. Estrogen levels rise and fall unpredictably rather than exhibiting their previous closely regulated cycles of increases and decreases.

Perimenopause is a unique time in the brain chemistry underlying mood.

Menopause itself is not identified until a woman has had 12 consecutive months with no menstrual periods. The extended transitional state of perimenopause can last for three to four years during which a variety of symptoms may occur, from merely annoying to very bothersome.

These symptoms may include hot flashes and night sweats, memory and concentration problems, vaginal dryness, unusual uterine bleeding, sleep disturbances, and mood disturbances, such as a tendency to cry for no clear reason.

The rate of clinical depression during perimenopause, even among women who have never experienced depression before, is unusually high compared with other life periods. Rates of first-time clinical depression among this group reach 16 to 17 percent.

A similar percentage of women get milder depressive symptoms, and experience mood changes. Fluctuations in hormone levels, specifically estrogen, are often blamed for these perimenopausal issues.

A Canadian study sheds light on one possible cause for the increase in depression among perimenopausal women — the brain protein, monoamine oxidase A (MAO-A).

Levels of MAO-A in brain tissue rise as estrogen levels decrease. It is known to impact other brain chemicals affecting mood stability. The study, by the Centre for Addiction and Mental Health (CAMH) in Toronto, investigated brain tissue during the estrogen fluctuations of perimenopause.

With PET (positron emission tomography) scans, researchers studied how MAO-A was distributed in the brains of 58 healthy women: 19 of reproductive age; 27 in the perimenopausal period; and 12 who were menopausal.

Women in perimenopause had MAO-A levels that were roughly twice those of other women. They had 34 percent more MAO-A in their brain tissue than the women of reproductive age, and 16 percent more than those who were post menopausal. The higher the MAO-A levels in the prefrontal cortex of their brains, the greater their tendency to cry.

It may be that mood regulation in perimenopausal women is influenced by MAO-A levels which in turn influence the brain chemicals that impact mood such as serotonin, norepinephrine, and dopamine.

The changing MAO-A levels reflect changes in estrogen levels. Once menopause is reached, levels of estrogen and brain chemicals stop fluctuating and brain neurochemistry stabilizes. But while women's bodies are going through perimenopause, they are on an estrogen rollercoaster and this can affect their mood.

These findings make it clear perimenopause is a unique time in the brain chemistry underlying mood. They suggest that a treatment plan for depression specifically focus on the challenging neurochemical imbalances related to perimenopause.

The investigators note, “This suggests a new mechanism for the exceptionally high prevalence of mood disorders during perimenopause, has potential implications for the timing and approach of HRT and raises new considerations for defining change in the brain relative to other physical changes during the perimenopause.”

Women who are experiencing distressing perimenopausal symptoms and changes in their moods or unusual tearfulness may wish to consult their health care provider to discuss possible interventions.

The study is published in JAMA Psychiatry.