Sex, Gender and the Brain: an interview with Dr. Maria Teresa Ferretti
Brain health and sex and gender differences represent a crucial and innovative area of study in modern medicine.
Understanding these differences is essential because sex, a biological concept, and gender, a socio-cultural construct, influence the prevalence, incidence, and progression of many brain diseases. Integrating sex and gender perspectives into research and clinical practice can lead to new discoveries and personalized treatments, advancing the field of precision medicine.
Senior neuroscientist and biomedical researcher Dr. Maria Teresa Ferretti discusses this in depth, illustrating how the integration of these differences can revolutionize brain care.
What is the difference between sex and gender, and what is Gender Medicine?
While used interchangeably in everyday language, sex and gender refer to two very different concepts in medicine. Sex is a biological concept, brought about by the expression of sex chromosomes and hormones; gender is the socio-economic/socio-cultural construct of being a man or a woman, according to a given society. Both sex and gender are determinants of health according to the WHO, and gender medicine is the branch of medicine dedicated to the study of how sex and gender differences impact our bodies in health and disease.
Why should biological sex and cultural gender be more present in research and clinical practice?
According to the World Health Organisation, both sex and gender are determinants of health. This means that — for both biological and cultural reasons — the diseases we get, the way we respond to treatments and even our access to healthcare services will be different depending on whether we are a man, a woman or belong to a sexual minority. Many fields of medicine still work under the assumption that ‘one-size-fits-all’, but this is simply not true and assuming that treatments optimised for white Caucasian males will work for everybody is leading to suboptimal care. Integrating sex/gender into research and clinical practice can help us to make new discoveries and personalise treatments towards Precision Medicine.
Are there any sex or gender differences that affect the prevalence and incidence of mental and neurological disorders?
Most neurological and psychiatric disorders show significant sex differences in terms of prevalence, incidence and frequency. Some of the most prevalent diseases worldwide — such as depression, migraines and dementia — overwhelmingly affect women, who represent two thirds of all patients. A greater prevalence of neuro-inflammatory conditions — such as multiple sclerosis — is also found in women. On the other hand, several diseases affect more men than women, including neurodegenerative diseases — such as Parkinson’s and ALS, but also glioblastomas and strokes in midlife.
Can you share any clinical examples in which sex differences significantly impact neurological conditions?
In many neurological diseases — such as migraines, epilepsy and multiple sclerosis —symptom onset and severity is profoundly affected by hormonal changes. As a result, puberty, pregnancy and menopause are windows of vulnerability for women, during which brain diseases can appear or be exacerbated. Symptom progression can also be different in men and women; for instance, in Alzheimer’s disease women initially compensate for the pathological changes and often miss an early diagnosis but then go on to deteriorate faster than men. In many cases, drugs used for neurological diseases have a less favourable safety profile in women than men; for instance, L-DOPA for Parkinson’s disease is known to induce more frequent and more severe dyskinesia in women.
What opportunities do you see for advancing research and awareness in this field? (Especially in terms of precision medicine).
Neurological and psychiatric diseases represent a massive unmet clinical need and cost to society — both in terms of direct costs but also the burden to families and caregivers. I think sex/gender sensitive research has a huge potential for innovating in this field and advancing Precision Medicine. Something as simple as stratifying the data of preclinical or clinical experiments by sex to look for potential sex differences can unveil drug effects that would be lost when pooling the data together or testing on only single-sex animals. The same stratified approach in biomarker research can lead to more precise diagnostic and prognostic tools, especially with predictive algorithms. It is therefore important to raise awareness amongst the scientific community, but also clinicians and patients, on sex differences in brain diseases.
With over 400 neurological disorders constituting the highest prevalence of disease, largest incidence of disability, and the fastest-growing cause of death among non-communicable diseases worldwide, Dr. Maria Teresa Ferretti underscores the critical importance of recognizing sex and gender differences in brain health. She emphasizes the urgency of health and gender equity in neurology and psychiatry and the need to address gender-related barriers to healthcare services. Ferretti advocates for patient involvement at every stage of the research process as a model for integrating sex and gender differences into research and clinical practice. By promoting precision and patient-centered medicine, the advancement of innovative diagnostic and prognostic tools could soon enable prevention, detection, diagnosis, and treatment tailored to each patient's unique profile.