CEREBRAL SEXUAL DIMORPHISM

Historically, research on the brain has focused primarily on male brains, especially in preclinical animal studies. In neuroscience publications, studies conducted exclusively on males outnumber those on females by an average ratio of 5.5 to 1. Both sex bias and the omission of sex in methods and analyses continue to persist across much of the neuroscientific literature, despite the now well-established reality of sexual dimorphism in the brain. Since much of the material we will examine is inevitably influenced, at least in part, by this predominance of male- based studies, we consider it important to provide an overview of what cerebral sexual dimorphism is and its main features.

What is cerebral sexual dimorphism?

Cerebral sexual dimorphism refers to the biologically determined differences between male and female brains (e.g., in specific regions, circuits, or neurotransmitters) that involve morphology, connectivity, physiological activity, and neurochemical profiles. These differences stem primarily from genetic factors (sex chromosomes) and from the action of gonadal hormones, which exert organizational effects during development and activational effects in puberty and adulthood.

What are the main morpho-functional differences?

The most evident difference between male and female brains is size, namely average volume, which largely reflects average body height. Since men are generally taller, their brains—like other organs such as the heart or hands—are slightly larger on average. Male brain volume averages about 1,260 cm³, compared with approximately 1,130 cm³ in females, corresponding to roughly 100 grams more brain tissue in the adult male brain.

However, when brain weight is considered relative to body weight, these sex differences disappear: the ratio of brain size to body mass is the same in men and women. Importantly, this difference in volume does not translate into a greater number of neurons in men. On the contrary, estimates suggest that female brains contain about 4% more neurons, more densely packed— particularly in neocortical layers II (external granular) and IV (internal granular). Women’s brains also tend to have a higher proportion of white matter compared to men. White matter— composed of communication structures such as neuropils, dendrites, myelinated axons, and glial cells—supports synaptic transmission, neural signaling, and neuronal nourishment and protection. A larger proportion of white matter is thought to facilitate synaptic exchange, especially between hemispheres.

Another prominent anatomical difference lies in the corpus callosum, the bundle of approximately 200–250 million white matter fibers connecting the left and right cerebral hemispheres. Radiological evidence indicates that the corpus callosum is significantly thicker in women, with about 30% more callosal connections. This likely results in faster and moresymmetrical interhemispheric transfer, with implications for functions such as language and face perception. Conversely, men show stronger bi-hemispheric involvement in mental rotation of three-dimensional objects. Neuroscientists suggest that male brains exhibit less interhemispheric connectivity overall. A recent imaging study reported greater intra-hemispheric connectivity in men, but greater interhemispheric connectivity in women, supporting enhanced cross-hemispheric communication in the latter. In short, the male brain appears to be organized around more localized and modular networks, whereas the female brain is characterized by higher interconnectivity and cross-modularity.

Why is studying cerebral sexual dimorphism important?

Neglecting sexual dimorphism in the brain has compromised not only our understanding of neuroscience (and human biology more broadly) by skewing existing knowledge, but also the effectiveness of pharmacological treatments. Most drugs have historically been tested primarily on men, resulting in therapies that are often less effective—and sometimes even harmful—for women.

Pain, for example, is a neurological signal that originates and is processed in the nervous system. Analgesic drugs therefore act not on the injury itself but on the brain and neural pain perception sites. A 2025 study published in Neuron showed that men and women activate different immune pathways in pain processing. In women, certain immune cells trigger leptin secretion, a hormone associated with heightened pain sensitivity. This helps explain why identical analgesic therapies may be less effective in women. Such findings, together with other dimorphism-related differences, suggest that many drugs developed on male models may not translate effectively to female patients. μ-opioids (e.g., morphine), mixed κ agonists (nalbuphine, butorphanol, pentazocine), certain NSAIDs (ketorolac, naproxen), as well as paracetamol and ibuprofen, are examples of analgesics that demonstrate reduced efficacy in women compared with men. Improved understanding of cerebral sexual dimorphism can help fill critical gaps in brain science and guide the development of more effective therapies for both sexes.

What broader applications does the study of sexual dimorphism have?

Knowledge of sexual dimorphism represents a crucial step toward deeper understanding of ourselves, humanity, and society. As such, it offers powerful tools and insights that can be applied across disciplines, including those shaped by social sciences such as economics and marketing.

In marketing, and especially in neuromarketing, researchers sometimes analyze sex/gender differences in responses to advertisements and creative stimuli (using EEG, fMRI, fNIRS, eye-tracking, or GSR). Some studies reveal distinct neural activation patterns between men and women. For instance, women may show stronger dorsolateral prefrontal activation whencexposed to certain types of advertising. Such findings are used to refine messaging and narrativecstrategies, not to reinforce the notion of “male vs. female” brains. Field research has also shown gender differences in visual attention to digital advertising, insights that are then applied to optimize layouts and placements.

While relying rigidly on cerebral sexual dimorphism as a guide for marketing campaigns would be scientifically unsound and potentially misleading, it nonetheless remains a valuable framework for better understanding target audiences, their needs, and the society in which they operate.

Bibliography

• “Neuroscienze e differenze sessuali” by Alice Mado Proverbio

• https://www.frontiersin.org/journals/psychology/articles/10.3389/fpsyg.2021.654360/full

• https://europepmc.org/article/MED/9620515

• https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/747596