The Relationship Between Estrogens and Depression

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To answer the question of whether conjugated estrogens like Premarin can cause depression or anxiety, we must first talk about what estrogen is. Estrogen is a group of hormones which play a vital role in women's sexual and reproductive health. They are often referred to as sex hormones because of this. Estrogen helps to regulate a woman's sexual development, as well as her ability to conceive and bear children.

Conjugated Estrogens

Premarin is a brand of conjugated estrogens, which are a type of hormonal medication containing a mixture of estrogens. In Premarin's case, these have been isolated from the urine of pregnant mares: PREgnant MARes' urINe. It is used to treat symptoms associated with menopause and other low-estrogen conditions, such as hot flashes and vaginal dryness. It is also used in the prevention of osteoporosis (thinning of the bones) after menopause, some breast, and prostate cancer symptoms, and certain premenopausal conditions.

The Link Between Estrogen and Mood

It is well known that estrogen affects depression and anxiety. Women who are in their peak estrogen-producing years or transitioning to menopause tend to be affected by these disorders more often than either men or postmenopausal women. In addition, when women are experiencing hormonal fluctuations, such as prior to their menstrual periods and after giving birth, they tend to be more prone to mood disorders.

Perhaps not too surprisingly, depression and anxiety are also potential side effects of medications like Premarin, which affect hormone levels. The reason that estrogen-containing medications have the potential to affect mood is that estrogen plays many roles in the body, affecting more than just the sex organs. It can exert effects on the urinary tract, the heart, the blood vessels, bones, breasts, skin, hair, mucous membranes, pelvic muscles, and the brain.

Though Premarin can cause the side effects of depression or anxiety, some studies have shown that women who take conjugated estrogen during late menopause and early postmenopause have markedly less depression and anxiety than those who received a placebo.

Estrogen's Effects on the Brain

Some of estrogen's effects on the brain and nervous system include:

  • Regulating neurotransmitter systems that affect mood, like serotonin, dopamine, epinephrine, and norepinephrine
  • Sensitivity to the fluctuation of estrogen levels in the amygdala, which is linked to mood regulation
  • Stimulating beneficial mood-related actions in the hippocampus

Some women may be exceptionally sensitive to changes in hormone levels, causing them to be more susceptible to depression when these levels are off.

Signs of Depression

While it isn't known how often women become depressed while using Premarin, it is a potentially serious side effect. Symptoms of depression include:

  • Sadness
  • Inability to enjoy things that used to be pleasurable
  • Fatigue or low energy
  • Problems with thinking, concentration, or memory
  • Feelings of guilt, worthlessness, or helplessness
  • Feelings of hopelessness
  • Problems with sleep
  • Problems with weight or appetite
  • Irritability or restlessness
  • Thoughts of death or suicide

If you are using Premarin and experience any of these symptoms, especially if they are accompanied by thoughts of death or suicide, you should immediately consult with your healthcare provider for advice.

If you or a loved one are struggling with depression, contact the Substance Abuse and Mental Health Services Administration (SAMHSA) National Helpline at 1-800-662-4357 for information on support and treatment facilities in your area.

For more mental health resources, see our National Helpline Database.

4 Sources
Verywell Mind uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. Cleveland Clinic. Estrogen & Hormones.

  2. Gleason CE, Dowling NM, Wharton W, et al. Effects of Hormone Therapy on Cognition and Mood in Recently Postmenopausal Women: Findings from the Randomized, Controlled KEEPS-Cognitive and Affective Study. PLoS Med. 2015;12(6):e1001833. doi:10.1371/journal.pmed.1001833

  3. Santoro N, Allshouse A, Neal-perry G, et al. Longitudinal changes in menopausal symptoms comparing women randomized to low-dose oral conjugated estrogens or transdermal estradiol plus micronized progesterone versus placebo: the Kronos Early Estrogen Prevention Study. Menopause. 2017;24(3):238-246. doi:10.1097/GME.0000000000000756

  4. Wharton W, Gleason CE, Olson SR, Carlsson CM, Asthana S. Neurobiological Underpinnings of the Estrogen - Mood Relationship. Curr Psychiatry Rev. 2012;8(3):247-256. doi:10.2174/157340012800792957

By Nancy Schimelpfening
Nancy Schimelpfening, MS is the administrator for the non-profit depression support group Depression Sanctuary. Nancy has a lifetime of experience with depression, experiencing firsthand how devastating this illness can be.