Is Biological Sex Binary? What Science Says

The claim “biological sex is binary” is a simplification that, while useful in everyday communication, does not capture the true complexity of biology. This article examines what constitutes biological sex, how its various components can be misaligned, and what this implies for understanding transgender and intersex people.

Biological Sex Is Not a Single Parameter

When people refer to “biological sex,” they often treat it as a unitary concept, as if there were a single biological switch. In reality, sex is a collection of independent characteristics that, in most people, align consistently but can diverge [1]:

• Chromosomal sex: the karyotype (typically XX or XY, but variants such as XXY, X0, and mosaicisms exist)
• Gonadal sex: the presence of ovaries or testes
• Hormonal sex: circulating levels of estrogen and testosterone
• Anatomical sex: internal and external genitalia
• Secondary sex characteristics: breasts, fat distribution, body hair, voice
• Neurobiological correlates: structural and functional brain characteristics associated with sex

As highlighted in a Nature article in 2015, these components are not always aligned, and the boundary between “male” and “female” is less clear-cut than commonly assumed [1].

Intersex Variations

Intersex conditions (today more accurately called “variations of sex characteristics” or DSD) are a concrete example of the complexity of biological sex. They include:

• Androgen Insensitivity Syndrome (AIS): individuals with a 46,XY karyotype who develop a completely female phenotype because their cells do not respond to testosterone
• Congenital Adrenal Hyperplasia (CAH): individuals with a 46,XX karyotype exposed to elevated prenatal androgen levels, who may develop ambiguous sex characteristics
• Klinefelter Syndrome (47,XXY): males with an extra X chromosome, who may present mixed characteristics

The prevalence of intersex variations depends on the definition adopted. Conservative estimates place it at around 0.018% of the population for conditions involving ambiguous genitalia at birth [10], while broader definitions that include all chromosomal, gonadal, and hormonal variations suggest a prevalence of 1-2% [1]. In any case, this represents a significant number of people who fall outside binary classification.

The Brain and Gender Identity

One of the most active areas of research concerns structural and functional brain differences in relation to gender identity [5]. Early studies in this field, such as Zhou et al. (1995) on the bed nucleus of the stria terminalis (BSTc), suggested that transgender individuals exhibited brain structures more similar to those of their experienced gender [8]. However, these pioneering studies had important limitations: very small samples, possible confounding effects of hormone therapy, and lack of independent replication.

More recent research has adopted more rigorous approaches. The ENIGMA study (2021), a mega-analysis involving over 800 transgender individuals, found that the brains of trans people exhibit patterns that fall between those typically male and female, but with great individual variability [2]. This finding is consistent with the “brain mosaic” concept proposed by Joel et al. (2015): human brains are not clearly “male” or “female” but present a unique combination of characteristics [3].

It is important to be cautious in interpretation: neuroanatomical research does not allow “diagnosing” gender identity from an MRI scan, and differences observed at the group level do not translate into reliable predictions at the individual level [9]. However, these studies confirm that gender identity has real neurobiological correlates [4].

The Biological Mosaic in Trans People

In light of this complexity, a transgender person can be described as someone whose biological sex exhibits an atypical alignment among its various components. In a trans woman on hormone therapy, for example:

• The karyotype is typically XY
• The hormonal profile is female
• Secondary sex characteristics shift toward the female pattern
• Hemoglobin and metabolism follow the female pattern
• Skeletal structure reflects the original pubertal development
• Brain structures show patterns that do not clearly correspond to either of the two typical categories [2]

This “mosaic” is not an anomaly: it is simply the result of the fact that the various components of biological sex are regulated by partially independent mechanisms [6].

Bimodal, Not Binary

The most accurate scientific position is not that “sex doesn’t exist” or that “sex is a continuous spectrum,” but that biological sex is bimodal: the vast majority of people cluster near one of the two poles (male or female), but significant variability exists, and some people occupy intermediate or atypical positions [1].

This distinction is important: recognizing complexity does not mean denying that in most cases binary classification is functional. It does mean, however, acknowledging that people who do not fit perfectly within this bimodality — whether intersex or transgender — do not contradict biology but express its natural variability.

Limitations of Current Research

It is important to note that many of the cited studies have limitations. Neuroimaging studies often have small samples and do not allow establishing causal relationships [9]. Estimates of intersex condition prevalence vary considerably depending on the criteria adopted [10]. The genetics of gender identity is still in an exploratory phase, and identified variants explain only a small portion of the observed variance [7].

These limitations do not invalidate the general conclusions — the complexity of biological sex is a matter of fact — but they call for caution in drawing overly definitive conclusions about specific mechanisms.