More Than XY and XX: The Biology of Sex and the Intersex Experience

by Priyasha Itani

“It is the policy of the United States to recognize two sexes, male and female. These sexes are not changeable and are grounded in fundamental and incontrovertible reality.”

On Jan. 20, 2025, President Donald Trump signed an executive order titled “Defending Women from Gender Ideology Extremism and Restoring Biological Truth to the Federal Government.” As outlined in Section 2, Policy and Definitions, the US Government now categorizes sex as the following:

“[...] (d) “Female” means a person belonging, at conception, to the sex that produces the large reproductive cell.

(e) “Male” means a person belonging, at conception, to the sex that produces the small reproductive cell. [...]”

In recent years, there has been a surge in debates surrounding the meaning of “sex.” Whether it is newspaper headlines, social media, or even now federal law, new and contradicting quasi-definitions are constantly being thrown at us. To make matters even more confusing, we are badgered by common phrases like “biology,” which have been reduced to buzzwords. However, it is times like these that we should ask ourselves, “Do I actually understand the biology of sex?”

Most commonly, we tend to conceptualize sex in a binary and concrete sense; that is, at conception, the presence of XX chromosomes will directly equate to females, and XY chromosomes will directly equate to males. While this understanding is not entirely false, it is crucial to recognize that, like all things in biology, sex is far more complicated. The process behind the development and presentation of sex extends further than conception, XX/XY chromosomes, and it is also a process that is not perfect. It is because of this complicated process that sex is actually categorized medically into three groups: male, female, or intersex. According to the Hudson Institute of Medical Research, “Intersex is an umbrella term for people whose reproductive organs, sexual anatomy or chromosome patterns differ from the biological definition of male or female. [...] Being intersex is a natural variation in humans, it does not mean there is something wrong.”

Chances are that you may have been unaware of intersexuality. That’s okay—the topic of biological sex can feel overwhelming considering the numerous misrepresentations of intersexuality in the media. However, approximately 1.7% of the global population have intersex traits, with an estimated 5.6 million being U.S. residents. Intersex individuals are real and are now experiencing growing barriers brought forth by institutions that ignore their existence. In the wake of this, it’s time that the general public recognizes this issue and we can do so in the very least by educating ourselves on the basics of biological sex.

To gain some insight, I spoke to Dr. Laurel Roberts, ecologist and teaching professor at Pitt. It is important to recognize that Dr. Roberts does not work with direct research on sexual dimorphism; however, through her experience teaching introductory level students in biology and human physiology courses, she is excited to provide digestible groundwork on biological sex for many who are unfamiliar with the topic.

To begin, we have to set a framework for what sex is and how it is categorized in the context of humans. Roberts explains her working definition, “generally based on which set of chromosomes you have. For humans, having the presence or absence of the Y chromosome determines whether or not you will develop what are the male structures, reproductive structures.” Although sex chromosomes initially determine sex, the process of sexual development and maturity is much more extensive and includes other factors. Dr. Roberts explains this process can be examined at three levels: genetic, morphological, and enzyme pathways that link the two. “We have the development of the internal reproductive structures [...] then externally [...] but we also have the secondary sex characteristics. [...] The collection of chromosomes determine the developmental path, but that's all happening, as we know, through the adrenal cortex.” With the onset of puberty and workings of the adrenal cortex, these secondary traits, which society often conflates with biological sex, becomes the most visible markers of sexual maturity.

To further elaborate on this concept, let’s examine the relationship between genetics, morphology, and enzyme pathways in sexual differentiation. The presence or absence of the Y chromosome, which occurs at conception, begins a pathway for the development of males and females, respectively. The Y chromosome has a sex determining gene, known as SRY, and the genetic makeup then triggers the release of androgens, which is associated with masculization. Until 7 to 8 weeks of gestation, fetuses share identical genitalia; however, the presence or absence of androgens will initiate the development of reproductive structures or primary sexual characteristics. For example, a fetus with XY should produce androgens, causing the gonads to develop into testes; on the other hand, a fetus with XX and no Y chromosome instead produces female sex hormones like estrogen, causing the gonads to develop into ovaries.

Furthermore, a similar relationship can be seen in sexual maturation, which causes the development of secondary sex characteristics, during puberty. As Dr. Roberts mentions, the enzymatic pathways are largely determined by the adrenal gland. There are numerous examples of this, however, this article will examine the conversion of testosterone to dihydrotestosterone (DHT), a more potent androgen that is responsible for masculinization and presentation of external genitalia and secondary characteristics like facial hair and vocal depth.

Despite the complicated jargon, biological sex develops through the influence of genetics, as well as other biological factors and pathways that are meant to work effectively and correctly to result in male or female morphology and secondary characteristics. However, again, like anything in biology, this process is prone to errors and redirection. Differences in sexual development (DSD) is the medical term behind intersexuality and accounts for the range of various conditions where an individual’s physical sexual characteristics do not align with typical male/female development. DSD can occur either at a genetic level or impact enzyme pathways.

At a genetic level, DSD can be caused by disruptions in the number of sex chromosomes that an individual may have. Roberts touches on this subject, noting that viable offspring “have at least one X chromosome, whether or not you have a Y.” This allows for multiple variations including XXX, XYY, XXY, and Turner Syndrome, in which individuals only have one sex chromosome (X). Individuals with Turner syndrome are often categorized as female at birth because genetically, they lack the Y chromosome and as a result, possess external female genitalia. However, they also have underdeveloped ovaries and an inability to produce the large reproductive cell, or ova, a trait that can not be determined until puberty. This is a direct and definitive contradiction to the Trump administration’s definition of the female sex, which falsely assumes a female’s ability to produce the large reproductive cell upon the meeting of XX chromosomes at conception.

Furthermore, DSD can also occur at an enzymatic level: “What we see in DSD is that there's the number of sex chromosomes, but there are also the enzymatic, the metabolic interactions, and those things are unpredictable” as Dr. Roberts states. Despite being XY or XX at conception, you can still develop malfunctions in enzymes or endocrine function that change your physiology. For instance, a deficiency in the 5-alpha-reductase enzyme can result in a medical condition known as guevedoce, meaning “testicles at 12.” Individuals with guevedoce are identified at birth as female because they appear to hold external female genitalia or ambiguous external genitalia, which is usually deduced to be the default female anatomy. However, genetically, they hold the Y chromosome and are male. Because of the deficiency in the 5-alpha-reductase enzyme, their bodies are unable to obtain enough of masculinizing hormones (DHT) to develop male genitalia. Roberts explains, “Many people now know that males can also produce estradiol (estrogen) and females produce testosterone. They may have heard that girls produce boy hormones, boys produce girl hormones, but what they don't understand is that cholesterol, which is common in cell membranes, is common for both pathways.” For example with guevedoce, that excess cholesterol gets pushed into producing more “girl hormones”, causing the presentation of more feminine physical sex characteristics. However, this gets halted when puberty causes a spike in DHT hormones and they develop male testicles, belatedly revealing that the individual is in fact male. This experience is unique to guevedoces and even when factoring just physiology, guevedoce can not be simplified into the categorization of only male or female.

On the same day that President Trump signed the executive order, the State Department eliminated the ability to update sex fields on passports. In the case of guevedoces, the ability to update sex on passports is essential. Genetic tests that can confirm the sex of a fetus (non-invasive prenatal testing) are an uncommon practice due to the minimal coverage from insurance providers, unless the mother is under certain risk factors that threaten the health of the fetus or there is a known history of DSD in the family. Thus, the sex of most infants is determined by the appearance of external genitalia by healthcare professionals. It is plausible for an individual, who unknowingly has guevedoce, to be assigned the sex of female at birth and also create a passport prior to the discovery of their DSD later with the onset of puberty. According to current law, they would not be able to change their sex on their passport. The categorization of females, that is, the sex that holds the X chromosome and does not undergo DSD, would be an unfair description of that individual.

Furthermore, the State Department has also eliminated the ability to list individuals as an X gender/sex on passports. This feature is key to the safety of intersex individuals and has been an issue that the community has spent years fighting for. Passports are a form of identification and can provide vital information in the midst of an emergency. From a health care perspective, “male” and “female” do not encompass the physiology of intersex individuals, which is already a broad enough term. This vagueness can possibly lead to health care professionals providing care under a false pretense of the patient’s background—care that could cause further harm. In the most basic sense, shouldn’t a person’s identification report their biology clearly and accurately?

If you are a reader who can not relate to the personal experiences of intersex people, it is important to remember the respect and common decency we owe one another. That entails educating ourselves on critical information needed to form opinions about the people around us and the legalities that will directly impact their lives. Dr. Roberts contextualizes this issue beautifully:

“The idea of discrimination against somebody because of genetic inheritance, nondisjunction, or some random mutation in an enzyme has put them in a category, and that offends me. You are who you are, and you should be allowed to blossom as who you are and contribute. We shouldn't try to force them into a certain category. We should study and understand and realize that people are incredibly diverse, and that's just the way it is.”

If you are a reader who is a part of the intersex community, I hope you know that there are still communities of people ready to support you. The following resources are local to the Pittsburgh area and are happy to offer you care if you so choose:

The Central Outreach and Wellness Clinic - https://www.centraloutreach.com/

The Persad Center - https://www.persadcenter.org/

Allies for Health and Wellbeing - https://www.alliespgh.org/

PFLAG - https://www.pflagpgh.org/

Numerous LGBTQIA+ organizations at Pitt which can be contacted via instagram: Rainbow Alliance (@rainbowatpitt), PRISM (@prismatpitt), SPEQTRM (@speqtrm), Out in Science, Technology, Engineering, and Mathematics (@ostematpitt).