INTERSTITIAL HYPOTHALAMIC NUCLEI III (INAH-3) AND GENDER IDENTITY: AN INTEGRATIVE REVIEW OF NEUROBIOLOGICAL EVIDENCE

• DOI: https://doi.org/10.22533/at.ed.8208112620017

• Palavras-chave: INAH-3. Hypothalamus. Gender Identity. Transgender People. Sexual Dimorphism. Neurobiology.

• Keywords: INAH-3. Hypothalamus. Gender Identity. Transgender People. Sexual Dimorphism. Neurobiology.

• Abstract:

  
  Gender identity, as a biopsychosocial construct, has been the subject of intense neuroscientific research in recent decades. This article consists of an integrative review of the literature with the aim of compiling and critically analyzing the evidence on the relationship between the Interstitial Hypothalamic Nuclei III (INAH-3) and gender identity. The search was conducted in the PubMed, Scopus, SciELO, and Lilacs databases, covering the period from January 2000 to February 2026. Twenty-two studies were selected, including postmortem, structural and functional neuroimaging, genetic, animal model, and systematic review studies, organized into five thematic categories: (1) Classical Morphological Evidence; (2) Functional and Connectivity Evidence; (3) Animal Models; (4) Genetic, Epigenetic Evidence, and Integrative Reviews; and (5) Critical, Clinical, and Social Perspectives. The results confirm the INAH-3 as the most robust structure of sexual dimorphism in the human brain, with significantly greater volume and number of neurons in cisgender men. In transgender individuals, particularly trans women (assigned male at birth who identify as women), a complete structural reversal of the INAH-3 is observed, resembling the female pattern, regardless of circulating hormones in adulthood. Studies of functional connectivity and white matter microstructure complement these findings, revealing unique neural signatures in trans individuals. Animal models with the Sagittal Nucleus of the Hypothalamus (SGN) provide functional support for the hypothesis of early hormonal organization. Critical analysis of the methodology points to limitations inherent in postmortem studies, such as small sample sizes and difficulty in controlling for confounding variables. It is concluded that INAH-3 is a central component of a broader neural network involved in gender identity, whose organization occurs early in development, possibly through hormonal and epigenetic mechanisms. The integration of this evidence reinforces the need for a multidisciplinary, ethical, and non-pathologizing approach to the health care of people with diverse gender identities.