Postmenopausal Hormone Therapy May Increase Mood Disorder Risk

This entry was posted in Mental Health on December 4, 2015 and modified on April 30, 2019

Hormone treatment that includes estrogen (or a combination of estrogen and testosterone) may substantially increase mood disorder risks in postmenopausal women, according to recent findings from a team of Swedish researchers.

Doctors sometimes recommend the limited use of hormone therapy for women who experience considerable discomfort while going through the prominent hormonal changes associated with menopause. In a study published in February 2015 in the journal NeuroImage, researchers from Sweden’s Karolinska Institute and University Hospital assessed the impact that estrogen-based hormone treatments may have on postmenopausal women’s chances of developing symptoms of a mood disorder (depressive illness or bipolar illness). These researchers concluded that estrogen–based treatments may significantly increase risks for mood disorders associated with changes in levels of a key chemical in the human brain called serotonin.

Serotonin, Sex Hormones and Mood Disorders

Serotonin is a naturally occurring chemical that all humans rely on for mood control, as well as for the regulation of such things as the daily sleep cycle and the efficient digestion of food. The vast majority of this chemical is manufactured by cells in the gastrointestinal system. However, roughly 10 percent of all serotonin manufacture occurs in the brain, and the brain only has access to its self-generated supply of the chemical. Deficits in brain levels of serotonin and/or damage in serotonin-producing cells can contribute to the onset of major depression and other forms of depressive illness, as well as to the onset of bipolar I disorder and other forms of bipolar illness. For this reason, doctors often use antidepressant medications called SSRIs (selective serotonin reuptake inhibitors) as mood disorder treatments. These medications produce their core benefits by increasing the brain’s serotonin levels.

In both men and women, sex hormones also make an important (and sometimes overlooked) contribution to mood stability and mental well-being. In women, menstruation-related, pregnancy-related and menopause-related changes in the levels of these hormones commonly increase depression risks and therefore help explain women’s disproportionate degree of exposure to depressive illness. Sex hormone-based differences may also contribute to a relatively rapid cycling between manic episodes and depressive episodes in women with bipolar illness. However, women don’t actually develop bipolar illnesses more often than men.

Postmenopausal Women and Hormone Therapy

Sharply reduced levels of the sex hormones estrogen and progesterone can lead to the onset of significant problems in menopausal or postmenopausal women, including such things as sleep disruption, hot flashes and uncomfortable or painful tissue changes in the urinary tract or the vagina. Doctors can relieve or reduce the severity of some of these symptoms by replacing lost sex hormone production with synthetically produced estrogen and/or a progesterone equivalent called progestin. In addition to women who naturally go through menopause, hormone replacement therapy can help women who experience abrupt-onset menopause as a result of going through surgical procedures that seriously decrease their estrogen and progesterone output.

Hormone Therapy and Mood Disorder Risks

In the study published in NeuroImage, the Karolinska Institute and University Hospital researchers used a small-scale project to assess the impact that hormone therapy can have on postmenopausal women’s levels of serotonin and subsequent degree of exposure to serotonin-related mood disorders. During the project, 10 generally healthy women who previously entered abrupt-onset menopause after having their ovaries removed were given three months of estrogen-based hormone therapy, as well as three months of therapy that included both estrogen and the male sex hormone testosterone (which naturally occurs in women in relatively small amounts). After each three-month treatment, the researchers used brain scans to measure each participant’s levels of a protein required for proper regulation of the brain’s serotonin levels.

The researchers concluded that the use of estrogen as a hormone therapy substantially reduced the efficiency of serotonin regulation in several parts of the study participants’ brains. They also concluded that the combined use of estrogen and testosterone had a similarly disruptive effect on regulation of this mood-controlling chemical. However, the researchers could not identify the specific reason why the use of estrogen or estrogen/testosterone interferes with the brain’s serotonin levels.

Overall, the study’s authors found that the use of estrogen-based hormone therapy may substantially increase postmenopausal women’s level of exposure to serotonin-related mood disorders. However, despite hormone therapy’s damaging impact on serotonin levels, they note that women who receive both estrogen and an SSRI antidepressant medication still commonly receive a clear treatment benefit for their depression-related symptoms.

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