Depression Causes: Hormones


Researchers have long wondered how hormones are related to the experience of depression.  Hormones are chemical messengers that travel through the body in the blood vessels.  Much like neurotransmitters such as serotonin work in the brain, hormones work elsewhere in the body by attaching themselves to the outsides of cells and initiating specific changes in the body. In trying to understand depression, researchers have focused primarily on three hormones that that are associated with depression—cortisol, estrogen, and thyroid stimulating hormone.

Cortisol. Cortisol has been dubbed the “stress hormone.” Much like the “chemical imbalance theory” of depression, work on hormones focused on trying to establish a connection between depression and hormone levels that were either too high or too low.  The majority of this work has focused on the intuitive idea that depression is caused by too much of the stress hormone, cortisol (Burke, 2005; Nemeroff, 1984).  Often times, this work references the hypothalamic-pituitary adrenal axis - or the HPA axis for short, which is a hormonal pathway in the body. Stress can cause several different glands to produce hormones that trigger a cascade of events along the HPA axis, which eventually stimulate the release of high levels of cortisol. However, although half of people have higher than average levels of cortisol, the other half have lower than average levels, which calls the cortisol theory into question (Thase, 1984).  Although it is unclear exactly how stress, cortisol and depression are all related, it is clear that stress early in life can severely disrupt the “stress hormone system” which increases risk for depression and other problems later in life.

Estrogen. Estrogen is a hormone produced by the ovaries in women. Fewer studies have been conducted on the relationship between estrogen and depression. There are three life phases that are associated with major changes in estrogen as well as frequent occurrence of depression—puberty, pregnancy, and menopause.  Although some have suggested that increases in estrogen during puberty (along with other hormones called follicle stimulating hormone and luteinizing hormone) may trigger depression, there are other factors likely contributing to depression risk during puberty. For example, changes in physical appearance may cause negative body image, early or late “bloomers” may feel insecure about being different than peers and teen years may bring an increase in stressful life events compared to childhood.

During the perinatal phase (pregnancy and postpartum), many women experience depression.  However, researchers have been unable to identify a strong link between estrogen or pregnancy-related hormones and depression (for review see: Zonana and Gorman, 2005). Similar to the problem of assessing estrogen and depression during puberty, it is very difficult to determine how much depression is due to changes in hormones versus other variables such as age, marital status, number of previous children, and breast feeding status. 

When women experience menopause and no longer ovulate, estrogen levels decrease and some researchers believe this change in estrogen levels can trigger depression.  In fact, several clinical trials using estrogen replacement therapy for depression have been conducted based on this idea.  Although the evidence is mixed, experts in this field generally agree that estrogen replacement therapy can have beneficial effects on mood and thinking but prolonged use of estrogen replacement can increase risk for developing some types of cancers.  With respect to it’s effectiveness for depression, the evidence is shakier and depends on a number of factors including depression history and timing of menopause (Morrison, 2006).

Thyroid Stimulating Hormone. For many decades, researchers have noticed the link between the thyroid and depression. The thyroid is a gland that shaped like a butterfly located in the neck.  Hormones produced by the thyroid are called thyroid stimulating hormones and control the body's metabolism—how fast calories are burned and how fast the heart beats. Two of the most common diseases of the thyroid are hypothyroidism, which occurs when too little thyroid hormone is produced, and hyperthyroidism, which occurs when too much thyroid hormone is produced. Hypothyroidism can look a lot like features of depression (changes in appetite, energy, and sleep) but the treatment for hypothyroid is quite different. For this reason, it is very important to “rule out” hypothyroidism when assessing depression to ensure that depressive symptoms are not being caused by problems with the thyroid. 

To learn more about hormones and the brain, check out the resources listed below.

Depression and cortisol responses to psychological

stress: A meta-analysis

Heather M. Burkea,*, Mary C. Davisb, Christian Ottec, David C. Mohra,d,e

Neuropsychopharmacology (2006) 31, 1097–1111. doi:10.1038/sj.npp.1301067; published online 22 March 2006

A Review and Update of Mechanisms of Estrogen in the Hippocampus and Amygdala for Anxiety and Depression Behavior

Alicia A Walf1 and Cheryl A Frye1,2,3,4

CNS Spectr. 2005 Jun;10(6):449-57.

Endocrinology of menopausal transition and its brain implications.

Genazzani AR1, Bernardi F, Pluchino N, Begliuomini S, Lenzi E, Casarosa E, Luisi M.

Estrogen, Menopause, and the Aging Brain: How Basic Neuroscience Can Inform Hormone Therapy in Women

John H. Morrison1, Roberta D. Brinton2, Peter J. Schmidt3, and Andrea C. Gore4