3.4: Biological Differentiation- From Binary to Spectrum

Internal Genitalia

Around week six, if the SRY gene is present and active (as discussed in Section 3.1), it triggers the development of the testicles from the previously undifferentiated gonads. The testes then produce two key hormones: Anti-Müllerian Hormone (AMH), which causes the Müllerian ducts (the precursors to the uterus, fallopian tubes, and upper vagina) to break down, and testosterone, which promotes the development of the Wolffian ducts into the epididymis, vas deferens, and seminal vesicles. Without SRY activation, the gonads develop into ovaries, the Müllerian ducts develop into the uterus and fallopian tubes, and the Wolffian ducts break down (see Figure 3.1).

External Genitalia

Around week eight, the hormone dihydrotestosterone (DHT) promotes the development of typically male external anatomy (the penis and scrotum). Without DHT, or with a system that is not sensitive to it, typically female external anatomy develops (the clitoris and labia). Importantly, all external genital anatomy develops from the same tissue, male, female or intersex. Therefore, the external genitals develop along a continuum rather than as a binary switch (see Figure 3.2).

This is also where hormone based intersex variations are important to consider because of their impact on external genital structures. Recall that Section 3.1 introduced chromosomal intersex variations. Now that we have covered hormones and prenatal development, we can look at intersex variations that arise from differences in hormone levels, exposure, and/or reception.

Figure 3.2. The Prader scale, used to describe degrees of virilization. Figure by Heland, Hewitt, McGillivray, and Walker, CC BY-SA 2.5, via Wikimedia Commons.

Hormone Based Intersex Variations

Though we have previously covered chromosome based intersex variations, we return to intersex variations here to cover those that involve hormone pathways behaving differently than expected.

Androgen Insensitivity Syndrome (AIS), approximately 1 in 20,000 to 1 in 64,000 XY births (Hughes et al., 2006), is when a person with XY chromosomes has cells that cannot respond to androgens (including testosterone). In complete AIS, the person develops typically female external anatomy (clitoris and vulva) despite having XY chromosomes and internal testes. In partial AIS, the body has some response to androgens, but not as much as a typical person with XY chromosomes. There can be a wide range of anatomical presentations with some appearing feminized similar to complete AIS while others may have a slightly more masculinized anatomy.

Congenital Adrenal Hyperplasia (CAH), approximately 1 in 15,000 births for the classic form, is characterized by adrenal glands that produce less cortisol (which regulates the stress response) and aldosterone (which regulates electrolytes) than typical. Those with CAH often produce excess androgens as the body’s way of compensating for low cortisol and aldosterone. This leads to the development of more male-typical external genitalia in those with XX chromosomes, while internal reproductive anatomy (uterus, ovaries) develops along female-typical lines. For those with XY chromosomes CAH does not really alter their typical sex development, so is not considered a difference in sexual development for them. Because CAH affects the body’s ability to regulate electrolyte levels, classic-CAH will typically be noticed at birth even in XY babies because low cortisol or aldosterone levels will cause vomiting, dehydration, and shock. Nonclassic-CAH is more common, approximately 1 in 1,000 births (Speiser et al., 2018), but mild enough that it may not be diagnosed until later in childhood or even adulthood.

DHT Deficiency (5-alpha reductase deficiency), is rather rare so the exact prevalence is unknown, though there are specific communities with higher rates (Dominican Republic, Papua New Guinea, and Turkey; Mendonca et al., 2016). This is characterized by a person with XY chromosomes developing female-typical external anatomy at birth because the body lacks the enzyme (5-alpha reductase) that converts testosterone into DHT. At puberty, when testosterone levels rise dramatically, these children develop more male-typical characteristics like a deeper voice and increased muscle mass. In the Dominican Republic and Papua New Guinea, where rates are high enough for a third sex to be recognized, the communities there have terms specifically for such children. “Guevedoche,” meaning “penis at twelve” in the Dominican Republic, and “kwolu-aatmwol,” meaning “into a male thing” in Papua New Guinea. The guevedoche and kwolu-aatmwol children apparently experience ambivalent sex-role socialization. In spite of this, these communities still only recognize binary (male/female) gender roles, and when the child undergoes male puberty they most frequently begin identifying as male (Fausto-Sterling, 2000).

Intersex Surgeries

When an infant's anatomy does not conform to binary expectations, physicians have historically performed cosmetic surgeries to 'normalize' genital appearance, sometimes without fully informing parents about the nature of the variation or the option to wait (Amnesty International, 2017). These decisions were often made under pressure, with parents told that surgery was medically necessary when it was simply cosmetic. Intersex advocacy organizations, including interACT (Advocates for Intersex Youth), have pushed for greater awareness, and an end to non-consensual cosmetic surgeries on intersex infants. Also keep in mind that intersex is not a gender identity. People who are intersex hold the full range of gender identities, just like people who are not intersex. The intersex variations covered here and in section 3.1 are not a complete list. For more education about the intersex community and Intersex activism, please check out the InterACT advocacy website.

Prenatal Hormones and Brain Development

So far we have discussed how hormones shape anatomy. But do prenatal hormones also shape the brain? The question of whether prenatal hormones can shape the brain has been the subject of debate. Some studies suggest that prenatal androgen exposure may influence brain organization, potentially contributing to later differences in behavior (Hines et al., 2015). Research with individuals who have CAH (who are exposed to higher-than-typical levels of prenatal androgens) has found some shifts in play behavior and interests that are typically associated with the other sex (Berenbaum & Hines, 1992), but subsequent studies have found only small gender effects (Dessens et al., 2005). However, some studies have reported that brain patterns in transgender individuals align more closely with their gender identity than with their sex assigned at birth (Sánchez & Vilain, 2013).

Recall in Chapter 1 the work of Joel and colleagues (2015) on cisgender brain patterns, suggesting that human brains are better described as "mosaics" of features rather than as distinctly "male" or "female." Differences between cis- male and female brain patterns tend to be small, with high overlap between sexes, and they cannot reliably predict any individual's gender identity. If there is so much overlap even in cisgender brains that gender identity cannot be predicted, this highlights the importance of being wary of neurosexism, the use of brain research to reinforce gender stereotypes or to suggest that gender identity must be validated by a brain scan (Fine, 2010). No one should need neurological evidence to have their gender identity respected. The brain research is interesting and ongoing, but must be understood among coexisting developmental, social and cultural processes.

Section Key Terms