As a woman in her early 20s, menopause seems to me like a mystical age free from pesky, cramp-filled visits from Aunt Flo. While it’s typical to think of hot flashes and mood swings as the only major side effects of menopause, that’s simply not the case — it’s not all fun and games on the journey to menstrual liberation!

Several changes occur in the body leading up to menopause even before it starts. This period is termed perimenopause, or “around menopause.” During this time period, declining estrogen levels cause a myriad of side effects. A recent publication by researchers at the University of Toronto asserts that clinical depression is one of these unwanted symptoms of perimenopause and proposes a contributing factor.

Dr. Jeffrey Meyer, associate professor at the Department of Psychiatry and the Department of Pharmacology & Toxicology at U of T, led the study, working with other scientists affiliated with U of T as well as the University of Leipzig. The study was published in JAMA Psychiatry last month.

According to Meyer, one of the main issues in women going through perimenopause is the abnormally high rate of clinical depression. The study shows a correlation between increasing levels of a protein, monoamine oxidase A (MAO-A), in the brain and the appearance of depression in perimenopausal women. The rise in MAO-A is believed to be caused by the drop in estrogen. Estrogen fluctuations are a defining characteristic of perimenopause, but it has been seen that even if the level of estrogen rises again, MAO-A levels will still remain high.

In the study, 58 women of various ages and reproductive stages underwent carbon 11-labelled harmine positron emission tomography (PET), which determined the amount of MAO-A in various regions of their brains. In perimenopausal women, it was found that their MAO-A levels were 34 per cent higher than women of reproductive age and 16 per cent higher than menopausal women.

It is important to understand why MAO-A is relevant for studying depression in the first place. “MAO-A metabolizes certain brain chemicals such as serotonin, norepinephrine, and dopamine…We know that if we deplete these chemicals, people get sad moods,” said Meyer.

He goes on to explain that we know this because of a drug called reserpine, which is used to treat high blood pressure. Reserpine depletes the aforementioned chemicals, causing patients on it to be frequently depressed. When reserpine use was stopped, depressive symptoms were alleviated. Additionally, certain diets that lack the precursors for these neurotransmitters are also seen to cause a depressed mood.

In a previous study conducted by Meyer’s team, a similar mechanism of MAO-A increase has been seen after childbirth, due to a sharp drop in estrogen levels. This is believed to be a factor in post-partum depression. In fact, the drop in estrogen levels is much sharper in post-partum than during perimenopause.

Meyer hopes to create dietary supplements that will help prevent unwanted effects of the MAO-A upswing during perimenopause. These supplements would likely contain precursors of dopamine, serotonin and norepinephrine, among other components. While this will not prevent MAO-A increase, it will diminish the risk of becoming clinically depressed. Additionally, it may be possible to use a different supplement that will cause MAO-A levels to normalise.

The team is also looking into hormone replacement therapy that will mitigate the estrogen decline, as a preventative measure before menopause begins. As such, the outlook is positive for treatment and prevention of perimenopause-induced clinical depression.