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Why Some Women in Midlife May Develop Psychosis

Estrogen may protect a woman from psychosis, but what happens at menopause?

Key points

  • Chronic psychotic disorders in women tend to be milder and occur later in life than for men.
  • Estrogen is thought to be the protective factor for women.
  • Women, unlike men, have a second lifetime risk window for developing chronic psychosis, at menopause.
Pheelings media/Shutterstock
Source: Pheelings media/Shutterstock

Psychosis is a set of symptoms such as hallucinations, disorganized thinking, and/or delusions that can be triggered for a variety of reasons. Changes in brain chemistry occur during certain life transitions that can predispose someone to developing a new psychotic disorder. For example, the transition between childhood and adulthood is a typical time that young men first develop schizophrenia. Even though women’s brains develop faster than men's, their risk window for a first episode of schizophrenia is older than men's, suggesting that women, for some reason, have protection from developing chronic psychotic disorders.

If women do develop schizophrenia, they tend to have a milder course than men and respond to lower amounts of medication, though this can partly be explained by average body size and how women metabolize medications.

Scientists point to estrogen as the obvious protective factor. This hypothesis would seem to be supported by the fact that times when women have relatively lower estrogen levels (premenstrual or postpartum), they are at higher risk for more symptoms of mental illness. Also, unlike men, women have a second risk period during life for developing schizophrenia at or around menopause, when estrogen levels drop for good. Women with schizophrenia that begins at the more usual early 20s to 30s tend to have lower levels of estrogen than average as well.

Of course, many other things can cause psychosis: drug use (especially inhalants, marijuana, or LSD/hallucinogens), infections (yes even COVID-19), brain tumors, brain inflammatory conditions, medications such as steroids, diseases of the thyroid. Even iron deficiency (which reduces the ability to make neurotransmitters) can increase the risk of developing psychosis in someone vulnerable to the condition. During menopause, women have disturbed sleep due to hot flashes, and poor sleep can also raise the risk of psychotic disorders.

If estrogen is protective, would this be a reason to use hormone replacement therapy (HRT)? These therapies are associated with higher risks of blood clots and cardiovascular events. However, both oral and transdermal estrogens have been added to antipsychotic medication to women with schizophrenia with benefits for symptoms. The selective estrogen receptor modulators, or SERMs, used now as treatments for estrogen-sensitive breast cancers, also have potential, given how they interact with key excitatory signaling molecules in the brain thought to be out of balance during psychosis, but these need to be studied in human trials. Interestingly, these medications also seem to have effects on serotonin signaling in mice brains, suggesting some effect on mood and anxiety disorders as well. In general, estrogens seem to decrease inflammation and increase neuron recovery and repair in the brain, which is a combination true of many psychotropic medications that help a variety of types of mental illness.

Midlife onset of a new psychotic disorder is rare, and everyone who develops symptoms at this time needs a full history and medical work-up to rule out the metabolic, autoimmune, or infectious causes of psychosis. The history will help find the risk factors for things like iron deficiency, poor sleep, drug use, family history of mental illness, and life stressors contributing to mental instability. The treatment is a combination of education, support, and usually, antipsychotic medication is necessary. Fortunately, women who develop psychosis at midlife tend to have a milder course and require less medication than those who develop psychosis earlier.

Copyright Emily Deans, M.D.

LinkedIn and Facebook image: Pheelings media/Shutterstock

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