Should we treat women with schizophrenia differently to men?

The brain as a unisex organ is a myth said Professor Iris Sommer, University Medical Center Groningen, Groningen, Netherlands in her plenary presentation. The brains of men and women are very different, and these differences have major implications for the management of patients with schizophrenia.

The brains of men and women are very different, and this has major implications for the management of patients with schizophrenia

Aspects of diagnosis and symptoms in women with schizophrenia

Gender differences in schizophrenia and its treatment are apparent over the course of the disease, but treatment of women with psychosis is less evidence-based than that it is for men, said Professor Sommer. One reason for this is that clinical trials of antipsychotics show a far from negligible gender bias, with women as an under-represented population.¹

Women are an under-represented population in clinical trials

Gender differences in schizophrenia were highlighted in a Finnish cohort study that investigated the clinical trajectory of more than 16000 men and women hospitalised for schizophrenia spectrum disorder (SSD) between 2000 and 2014.² In this study, in contrast to men who were typically (and as expected) diagnosed in their early 20s, women with schizophrenia were diagnosed at any age throughout life.²

In a study, men were typically diagnosed in their early 20s, while women were diagnosed at any age throughout life

Symptoms of psychosis also evolve differently in women than in men, explained Professor Sommer, and affective symptoms are much more common in women. In the Finnish cohort, affective symptoms were diagnosed in 62% of women compared with 39% of men prior to hospitalisation for SSD.²

Affective symptoms are more commonly diagnosed with schizophrenia in women

Estrogen levels should be considered when treating women with schizophrenia

In addition to brain differences, men and women exhibit variances in physiology including differences in body composition and hormonal transitions as well as differences in pharmacokinetics and pharmacodynamics. These differences affect drug absorption, distribution, and metabolism.³ Higher drug plasma levels, for instance, can increase the risk of adverse events in women.³

Women typically do better than men in early-phase schizophrenia

The female hormone estrogen plays a particular role in gender differences with respect to antipsychotic medication through its effects on the hepatic cytochrome (CYP) system. Drug plasma concentrations are typically higher in females when hormone levels are high, for instance, prior to the menopause. Estrogen can also modulate the effect of dopamine agents by increasing D2 receptor sensitivity and estrogen deficiency can lead to an increase in psychotic symptoms.³ This may be a reason why women typically do better than men in the early stages of the disease compared to men, explained Professor Sommer. 

Hormone replacement and estrogen-like augmentation therapies have potential in the management of women with schizophrenia.