The largely binary nature of biological sex and its conflation with the socially constructed concept of gender has created much strife in the last few years. The notion of gender identity and its differences and similarities with sex have fostered much scientific and legal confusion and disagreement. Settling the debate can have significant repercussions for science, medicine, legislation, and people's lives. The present review addresses this debate though different levels of analysis (i.e., genetic, anatomical, physiological, behavioral, and sociocultural), and their implications and interactions. We propose a rationale where both perspectives coexist, where diversity is the default, establishing a delimitation to the conflation between sex and gender, while acknowledging their interaction. Whereas sex in humans and other mammals is a biological reality that is largely binary and based on genes, chromosomes, anatomy, and physiology, gender is a sociocultural construct that is often, but not always, concordant with a person' sex, and can span a multitude of expressions.

• Keywords
• Binary, Gender, Intersex, Sex, Sexual orientation, Spectrum,
• MeSH
• Gender Identity * MeSH
• Humans MeSH
• Sex Characteristics MeSH
• Sexual Behavior psychology   MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

In addition to primary reproductive functions, gonadal hormones play an important role in an array of neural mechanisms across the human lifespan. The ageing-related decline in their activity has been linked to the deterioration of cognitive functions in otherwise healthy women, associated with menopause transition, contributing to higher incidents of post-menopause dementia. Given the growing utility of gonadal steroids for birth control, as well as for compensatory treatment of menopause and oophorectomy symptoms, and adjuvant transgender therapy, their long-term effects on neural mechanisms warrant comprehensive assessment. In this article, we present an ageing perspective on the cognitive outcomes from contraceptive and replacement therapeutic use of gonadal hormones and discuss their effects on the risk of developing Alzheimer's and Parkinson's dementia. Despite rising data supporting the ameliorative effects of reproductive hormones on cognitive facilities, their impact varies depending on study design and type of intervention, thus, implying dynamic neuro-endocrine interactions with complex compensatory mechanisms. Elucidating differential effects of reproductive hormone adjustments on cognition with underlying mechanisms is expected not only to shed light on important aspects of brain ageing and dementia but to facilitate their use in personalized medicine with improved safety margins and therapeutic outcomes.

• Keywords
• Cognitive decline, Contraception, Gender transition, Healthy ageing, Hormone replacement therapy, Neuroprotection, Oestrogen, Transgender,
• Publication type
• Journal Article MeSH
• Review MeSH