Should Men and Women with Psychosis Be Treated Equally?
- Bodyl Brand
- 1 day ago
- 5 min read
More than a century ago, psychiatrists spoke of ‘climacteric insanity’: the strange and sudden madness said to strike women at the end of their reproductive years. Physicians in the late 19th century described vivid delusions, sleeplessness, and emotional turmoil appearing ‘at the change of life’, when the female body ‘lost its balance’.
A hundred and fifty years later, we still see the same pattern: the transition through menopause can trigger new or worsening symptoms of psychosis. And yet, we still do not fully understand why this happens or how best to treat it.
My path to studying psychosis in women
My name is Bodyl and I am a postdoctoral researcher at the University of Oxford. My work centres on understanding psychosis in women, and improving treatment options for the changing vulnerability we see across the female lifespan. My interest in this topic began, perhaps unconsciously, with my own experience of how changes in sex hormones during my menstrual cycle affected how I felt and thought. This made me curious about the subtle ways biology shapes our mental state.
During a clinical placement, I met people with psychosis and was fascinated by how different it could look from one person to another. At the same time, I noticed clear differences between men and women in how the illness manifested and evolved.
There, and also later during my PhD, I began to see consistent patterns. Young male patients were severely impacted by psychosis, while older males seemed to have reached a more stable stage of illness. Female patients, in contrast, tended to do relatively well earlier in life, but I noticed more instability in those who had reached midlife.
The oestrogen protection hypothesis
Clearly, I was not the first to notice this female-specific deterioration after midlife. The 19th Century observations of menopause-associated “instability” have been cemented by large-scale studies showing a second peak of psychosis in women around midlife. In the 1980s and 1990s, scientists also began to uncover that oestrogen does far more than regulate reproduction. Oestrogen shapes the brain by protecting brain cells from damage and supporting neural plasticity, (the brain’s ability to reorganise itself by forming new connections). These observations led to the oestrogen-protection hypothesis - that oestrogen has a protective effect, shielding women from psychosis when levels are high.
Menopause and psychosis vulnerability
Oestrogen levels are not constant throughout life. For example, in menopause oestrogen levels signficiantly reduced.
Women enter the menopausal transition (‘perimenopause’) around age 45 and reach menopause (12 months without menstruation) at about 50. The average female life expectancy is around 75, meaning that women spend roughly 1/3 of their lives in this postmenopausal stage – a proportion that will only increase as life expectancy rises.
Changes in treatment effectiveness around menopause
Despite extensive evidence for oestrogen’s protective effects on the brain and women’s increased vulnerability to psychosis around midlife, it remains unclear how treatment responses change during this period. Understanding how reaching midlife affects treatment response could help tailor more effective care for women with psychosis.
In one of the studies conducted during my PhD, we looked at how treatment for women with schizophrenia changes as they reach menopause. We used nationwide data from Finland, following over 61,000 people (both male and female) diagnosed with schizophrenia or related disorders between 1997 and 2017. We looked at how each individual’s risk of being hospitalised changed when they were taking antipsychotic medication compared to when they were not. We did this by comparing the risk of psychotic relapse between men and women above and below the age of 45.
Our findings were striking; women over 45 had a markedly higher risk of relapse than all three other groups. This suggested that after reaching menopausal age, women become significantly more vulnerable to psychotic relapse, and that the effectiveness of these medications may shift over time and across different stages of life.
Interpreting our findings
The decline in oestrogen around menopause offers an obvious biological explanation for this female- and age-specific vulnerability. But, it is unlikely to be the whole story. Reaching midlife and menopause also involve psychological and social transitions which may contribute to this increased vulnerability to psychosis (see also this piece by Dr Alice Onafrio).
Most importantly, our findings suggest that our understanding of how to best treat women with psychosis at this stage of life is still limited, and that current approaches may fail to address the complex, interrelated factors facing women.
You might wonder – how is that possible? The reason lies in the long-standing sex bias in medical research. Across nearly all health disciplines, women have historically been underrepresented in preclinical and clinical studies, as previously been discussed by Samrina Sangha for ITM. For decades, new drugs were tested almost exclusively in men, with the assumption that results would automatically apply to women too. While things are improving, the female sex remains under-represented in many studies. In psychosis research, the problem is even more pronounced: most clinical trials include participants aged 18-50, effectively excluding postmenopausal women.
Our current treatments are therefore based largely on a male body of evidence and thus sex-specific presentation and treatment of psychosis remain underrepresented in clinical training and treatment guidelines, perpetuating gaps in care and awareness among healthcare professionals.
Steps towards female-specific, hormone-informed care
The results of our study were striking and made us wonder whether the increased risk after midlife could be reduced with different treatment approaches. With the oestrogen protection hypothesis in mind, we investigated whether oestrogen-based menopausal hormone therapy (MHT - widely used since the 1960s to treat menopausal symptoms) might help to reduce psychosis relapse in women.
Using a cohort of 3488 women aged 40-62, we compared periods where they were taking MHT with periods where they were not. We found that the use of MHT was associated with a 16% decrease in risk of psychotic relapse. MHT may therefore help to counter the reduced effectiveness of standard antipsychotic treatment after menopause, pointing to a promising female-specific approach to improving outcomes in psychosis.
Together, these studies indicate that current psychosis treatments are not sufficiently tailored to the female body and brain. Yet the results offer hope: we may be able to treat, or even prevent, this menopausal worsening by harnessing the protective effects of oestrogen and developing female-specific treatment strategies.
Why equal treatment isn’t always fair
There is still so much to explore when it comes to female-specific treatment strategies for psychosis, and potentially other psychiatric disorders.
We need to move away from the assumption that if something works for men, it will work for women. We must begin to account for how different reproductive life phases shape vulnerability and treatment response – and design care that interacts with and accounts for those changes.
Men and women should not be treated equally. They should be treated fairly – with care that is shaped to male and female bodies, so that both can receive the treatment they need and deserve.
