Gender and sex are often spoken of as simple, fixed categories, but research in biology, neuroscience, and the social sciences reveals a much more complex picture. In this class, we will learn how gender and the brain are connected through biology, society, and lived experience. We will explore how sex exists on a spectrum not just male or female and how intersex variations highlight natural human diversity. We will also examine how gender is a social construct shaped by culture, history, and identity, and how neuroscience shows that the brain plays an important role in gender identity. Together, we will look at transgender and nonbinary experiences, the science behind gender diversity, and why affirming care and inclusion are essential for mental health and well-being. 

Sex refers to the biological and anatomical characteristics determined at conception, which include sex chromosomes (such as XX, XY, and other variations like XXY, X0), gonads (ovaries or testes), hormones (testosterone, estrogen, and progesterone), and internal and external reproductive anatomy (genitalia). 

At birth, most individuals are classified as either male or female based on external genitalia a designation known as “sex assigned at birth” (often noted as AFAB—assigned female at birth—or AMAB—assigned male at birth). However, biology is more complex than this simple binary classification. Sex exists along a spectrum rather than a strict binary, as some people are intersex, meaning their biological traits do not fit typical definitions of male or female. 

At the same time, sex is not only biological; it is also shaped by culture, history, and politics. For instance, societies determine the social norms and legal categories used to enforce the male/female binary, often dictating which biological variations require medical intervention or social accommodation. 

Intersex is a general term that encompasses a range of conditions in which a person is born with reproductive or sexual anatomy that does not fit typical male or female categories. These conditions are sometimes referred to as Differences of Sex Development (DSD) in a medical context and include variations like Androgen Insensitivity Syndrome (AIS) or Congenital Adrenal Hyperplasia (CAH). Some intersex people may also have mosaic genetics, where some cells carry XX chromosomes while others carry XY. Importantly, intersex traits may not always be apparent at birth; they might be discovered later during puberty, adulthood (such as when experiencing infertility), or even after death during autopsy. It is also essential to recognize that intersex is not a single “natural category” but rather a socially constructed term used to describe real biological diversity. In practice, different cultures and medical systems define intersex in different ways. A helpful analogy compares sex to the color spectrum: while colors exist as natural wavelengths, distinctions such as “red” versus “red orange” are made depending on social context and necessity. Similarly, societies decide when and how to label variations as “male,” “female,” or “intersex”. 

Some transgender individuals may experience gender dysphoria, which is distress that arises when one's gender identity does not align with their assigned sex, though not all do. Others may instead experience gender minority stress due to chronic stigma and discrimination. These terms underscore the fact that gender identity is about an individual's sense of self, not about who that individual is attracted to (sexual orientation). 

Gender identity is a person’s deep, internal sense of who they are: male, female, both, neither, or another identity—which may or may not correspond to the sex they were assigned at birth. 

• Cisgender: When an individual’s gender identity aligns with their assigned sex.
  Example: Emma was assigned female at birth and identifies as a woman. She describes never questioning her gender identity, which makes her cisgender. 

• Transgender: When an individual’s gender identity does not align with their assigned sex.
  Example: Laverne Cox, an Emmy-nominated actress, was assigned male at birth but identifies and lives as a woman. She often speaks publicly about her journey as a transgender woman. 

• Nonbinary: People who identify outside of the male/female binary.
  Example: Actor Lachlan Watson identifies as nonbinary and uses they/them pronouns, sharing that their gender exists beyond traditional categories. 

• Gender-fluid: Someone whose identity shifts over time.
  Example: Ruby, a college student, sometimes identifies as female and at other times as nonbinary, adjusting their pronouns depending on what feels right in that season of life. 

• Agender: People who do not identify with any gender.
  Example: Jay explains, “I don’t feel a connection to being male or female—I just see myself as me,” reflecting an agender identity. 

• Demigender: A partial connection to a gender.
  Example: Alex identifies as demiboy, meaning he feels partially connected to being a boy, but not entirely. 

• Femme: A reclaimed identity term often used in queer cultural politics to express femininity.
  Example: A queer individual may identify as femme to highlight their gender expression as feminine, even if they do not identify as a woman. 

Respecting a person’s affirmed name and correct pronouns (she/her, he/him, they/them, ze/zir, or titles like Mx.) is essential for recognition and inclusion. For instance, using the pronouns “they/them” for singer Sam Smith validates their nonbinary identity.

Sexual orientation is separate from gender. It refers to patterns of attraction,emotional, romantic, or sexual—toward others. Common identities include heterosexual, gay, lesbian, bisexual, and pansexual/omnisexual (attracted to people regardless of gender). Asexual individuals experience little or no sexual attraction, while aromantic individuals may lack romantic attraction. The umbrella term queer is widely used today to signal fluidity and resistance to rigid categories, though some still find it offensive given its history. LGBTQIA+ (Lesbian, Gay, Bisexual, Transgender, Queer/Questioning, Intersex, Asexual/Agender/Aromantic, and more identities) is an inclusive acronym that recognizes diversity in sexual and gender identities. 

While sex provides a biological foundation, gender is shaped by the complex interaction of biology and lived experience, including how the brain contributes to identity. Neuroscience suggests that the brain plays a significant role in cementing one's gender identity. 

Studies indicate that gender identity is correlated with specific structural and functional brain patterns. These differences are often more aligned with an individual's self-identified gender than with their sex assigned at birth, with some brain structures and activation patterns resembling those of cisgender individuals of the same gender identity. This suggests a biological component to gender identity that is separate from external anatomy. 

Moreover, life experiences profoundly shape one's understanding of gender. The brain's plasticity, its ability to change and adapt, means that cultural expectations, social interactions, personal exploration, and affirmation (or lack thereof) are constantly influencing how an individual understands and expresses their gender. The brain's structure can even be measurably altered by hormonal exposure and life events, such as those related to gender affirmation. Gender identity, therefore, emerges from the interplay between an individual's innate biological foundations and their continuous psychological and social development. This makes gender a profoundly personal, internal truth that is both rooted in the body and mediated by the world around us. 

People can realize that they are transgender at any age. For some, awareness begins in early childhood they may say they always “just knew” their gender identity. Others may need more time, discovering or naming their transgender identity later in adolescence or adulthood. Still others may feel for years that they do not “fit in” with the gender they were assigned at birth, but may not fully understand why until they encounter language, communities, or role models that reflect their experiences. It is up to the individual to decide. Sometimes people try to avoid thinking about their gender identity due to fear, shame, or confusion. However, attempting to repress or change one’s gender identity is not effective and can cause significant emotional and mental distress. Increased visibility of transgender people in the media and in communities has helped many individuals recognize their own experiences, feel less isolated, and find the courage to share their identity with others. 

Gender dysphoria is a feeling of distress that can occur when a person’s gender identity differs from the sex assigned at birth. While some transgender and gender-diverse people may experience gender dysphoria at certain points in their lives, others feel comfortable in their bodies and identities and may not experience dysphoria at all. Importantly, gender dysphoria is distinct from gender nonconformity. It refers specifically to the psychological distress that arises from the incongruence between one’s internal gender identity and assigned sex. 

A formal diagnosis of gender dysphoria is included in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), published by the American Psychiatric Association. The purpose of this diagnostic category is not to pathologize gender identity itself but rather to help people experiencing distress access appropriate healthcare and treatment. In this context, the focus is on the distress as the issue, not the identity. 

Symptoms of gender dysphoria may vary and often involve a strong, lasting desire to be another gender, accompanied by significant distress when there is a mismatch between one’s identity and physical body. These feelings may emerge in childhood and persist into adolescence or adulthood, though they can also fluctuate over time. For some individuals, dysphoria intensifies with puberty, while others may not experience it until later in life. Teens might share their feelings directly with parents or healthcare professionals, though some may present with symptoms of mood disorders, anxiety, or depression, or may struggle with school and social relationships. 

• Example: A transgender man may feel discomfort being referred to as “she” or may experience distress related to body features such as breasts that don’t match his male identity. 

Not all transgender people experience dysphoria. Some instead report gender minority stress, which comes from societal stigma and discrimination. 

• Example: A nonbinary teenager may feel constant stress when teachers refuse to use their pronouns, not because they feel internal conflict about their gender, but because of external rejection. 

These examples highlight that gender identity is about a person’s internal sense of self—not their sexual orientation, which refers to who they are romantically or sexually attracted to. 

Recognizing and affirming one’s gender identity often requires deep reflection. For many transgender people, beginning transition whether socially (changing name, pronouns, clothing) or medically (hormones, surgery) is a profound step toward authenticity. Yet coming out can involve risks, including stigma, discrimination, or even harassment. Family, friends, coworkers, or classmates may or may not be accepting, which creates fear of rejection. Despite these challenges, many transgender people describe embracing their true gender identity as life-affirming, and in some cases, life-saving, because it allows them to live authentically and improve their overall mental health and well-being. 

• Gender identity is how you know yourself on the inside (man, woman, both, neither, or another gender). 

• Sexual orientation is about who you’re attracted to. 

For example: A transgender man (someone who was thought to be female at birth but knows he is male) might be attracted to women (straight), to men (gay), or to people of any gender. Just like anyone else, transgender people can have any sexual orientation. 

Transgender vs. Intersex 

These two words mean different things: 

• Transgender: A person whose gender identity doesn’t match the sex they were assigned at birth. 

• Intersex: A person born with physical traits (like anatomy, hormones, or chromosomes) that don’t fit typical definitions of “male” or “female.” 

For example, some intersex people might have XY chromosomes (often linked to males) but have female anatomy. Many intersex people grow up identifying as the gender they were raised as, but some later realize it doesn’t match their internal sense of self. 

Important: A person can be both transgender and intersex, but most are one or the other. 

• Gender non-conforming means someone doesn’t fit society’s stereotypes about how men or women “should” look or act. 

• Example: A woman might have short hair, wear suits, and play sports that are seen as masculine, but still identify as a woman. 

• The word “tomboy” is often used for girls who are gender non-conforming. 

Not all gender non-conforming people are transgender. And some transgender people choose to express themselves in ways that match the gender they live as. 

• Counseling that tries to change someone’s gender identity is often called conversion therapy or “conversion practices.” Research shows these efforts don’t work and can cause serious harm. Major medical groups, including the American Psychiatric Association, strongly oppose them because telling someone that their true gender identity is “wrong” can lead to depression, anxiety, substance use, self-hatred, and even suicide. 

• A new study published in The Lancet Psychiatry found that LGBTQIA+ people who experienced conversion practices were more likely to have symptoms of depression, post-traumatic stress disorder (PTSD), and suicidality. The study, which surveyed over 4,400 people in the United States, showed that those who had been subjected to both sexual orientation and gender identity conversion practices experienced the greatest harm. 

• Ask—don’t assume. Gender identity is internal and cannot be “read” from appearance or voice. The only way to know someone’s gender and pronouns is to ask, and to recognize these may change over time. 

• Separate sex from gender. Sex (chromosomal, hormonal, reproductive traits) and gender (identity) are distinct; both can be nonbinary. Clinical forms and conversations should reflect this distinction.

• Create an affirming environment. Use inclusive intake forms (chosen name, pronouns, gender identity and sex assigned at birth), clear nondiscrimination signs, gender-neutral restrooms, and staff training in affirming language and trauma-informed care. 

• Address disparities directly. Transgender people experience higher rates of mistreatment in healthcare settings and elevated risks for depression, suicidality, substance use, HIV/STIs, cardiovascular concerns (in some contexts), and violence—especially for trans people of color. Affirming care and access to services reduce these risks. 

• Communication & documentation 

  • • • • Introduce yourself with your pronouns; ask and document the patient’s name/pronouns. Mirror their language for body parts when possible (Bhatt et al., 2022). 

        • Update charts to surface chosen name/pronouns prominently; avoid deadnaming in auto-text. 

• Preventive care & screening 

  • • • • Offer age- and organ-based screening (e.g., cervical cancer screening if a cervix is present; breast cancer screening based on breast tissue; prostate considerations if a prostate is present), using sensitive, low-trauma options when available (e.g., self-swabs). 

        • Take a behavior-based sexual health history; don’t assume partners or practices. Offer appropriate site-specific STI screening and prevention (e.g., HPV vaccination; HIV testing; PrEP/PEP when indicated). 

• Mental health 

  • • • • Screen for depression, anxiety, trauma, tobacco/substance use, and suicidality. Minority stress and discrimination elevate risk; affirming relationships, psychotherapy (including CBT), and access to gender-affirming treatments reduce symptoms and suicide risk. 

• Trauma-informed exams 

  • • • • Explain what you’re doing and why; ask permission before touch; offer options, pauses, and chaperones; consider smaller speculums or alternative positions to reduce dysphoria. 

• Access & advocacy 

  • • • • Many patients face insurance denials or administrative barriers. Provider letters and coordinated referrals can unlock coverage for hormones/surgeries and reduce harm from unsafe, non-medical routes. 

• Hormone therapy (feminizing/masculinizing) can improve quality of life and reduce dysphoria; requires monitoring (e.g., metabolic, cardiovascular, bone health) and patient education. 

• Gender-affirming surgery (e.g., chest reconstruction, vaginoplasty, phalloplasty) is associated with high satisfaction and reduced dysphoria; complication profiles vary by procedure; regret rates are low in the literature. Access is often limited by policy and insurance hurdles—where advocacy matters.

Transition is personal and flexible there is no single “right” order or required set of steps. People typically begin by exploring gender identity through self-reflection, community support, and (when helpful) work with a gender-competent therapist; this phase can take months to years. Health systems should validate identities without imposing unnecessary gatekeeping. 

Common Components (Mix & Match, up to the individual) 

1) Social transition 

• Presenting part- or full-time in one’s affirmed gender (clothing, hair, name, pronouns). 

• Techniques and tools some people use: packing, tucking, binding, breast/hip/buttock prostheses. 

• Coming out to family, friends, school/work, and updating day-to-day communication. 

2) Legal transition 

• Updating identity documents (name, gender marker) to reduce mismatch-related stress and barriers in daily life. 

3) Medical transition (individualized, not required) 

• Hormone therapy (estrogen or testosterone) using informed-consent or referral pathways; ongoing monitoring of risks/benefits  

• Hair removal, speech/voice therapy, and other supportive services  

• Fertility preservation (sperm/egg/embryo banking) before hormones or surgeries that may affect fertility 

• Gender-affirming surgeries (e.g., chest reconstruction/augmentation; vaginoplasty; phalloplasty/metoidioplasty) for those who want them. Programs follow WPATH SOC-8 assessment standards; satisfaction and quality-of-life generally improve after surgery  

Key clinical point: Screening and preventive care should be organ-based and trauma-informed (e.g., cervical screening if a cervix is present; discuss alternatives like self-swabs when appropriate). 

• Assessment focuses on capacity and preparedness (e.g., expectations, aftercare plan, support for transport/pharmacy/visits), aligned with WPATH SOC-8. Some procedures may require a behavioral health evaluation and/or a period of living in affirmed gender, with flexibility for medical or contextual reasons. 

Multiple longitudinal and prospective studies link access to gender-affirming medical care (puberty blockers/hormones) with lower odds of depression and suicidality among transgender and nonbinary youth; adult studies also associate gender-affirming surgeries with improved mental health outcomes. Evidence for youth continues to evolve; leading guidelines (WPATH SOC-8) emphasize individualized, multidisciplinary care and ongoing research.  

By the end of this class, we will have learned that sex and gender are more complex than simple binaries. We will understand that biology, brain science, and lived experiences all work together to shape identity. Most importantly, we will recognize the importance of respect, affirmation, and inclusion in supporting the well-being of all people, especially those who are transgender and gender-diverse.  

Aulette, J. R., Wittner, J., & Blakeley, K. (2009). Gendered worlds. Oxford University Press. 

Blackless, M., Charuvastra, A., Derryck, A., Fausto-Sterling, A., Lauzanne, K., & Lee, E. (2000). How sexually dimorphic are we? Review and synthesis. American Journal of Human Biology, 12(2), 151–166. https://doi.org/10.1002/(SICI)1520-6300(200003/04)12:2<151::AID-AJHB3>3.0.CO;2-F 

Davies, S. G. (2007). Gender diversity in Bugis society. Indonesia and the Malay World, 35(102), 289–305. https://doi.org/10.1080/13639810701569414 

Fausto-Sterling, A. (2000). Sexing the body: Gender politics and the construction of sexuality. Basic Books. 

Fausto-Sterling, A. (2019, October 25). Why sex is not binary. The New York Times. https://www.nytimes.com/2018/10/25/opinion/sex-biology-binary.html 

Intersex Society of North America. (n.d.). What is intersex? https://isna.org/faq/what_is_intersex/ 

Laumann, E. O., Gagnon, J. H., Michael, R. T., & Michaels, S. (1994). The social organization of sexuality. University of Chicago Press. 

Lindsey, L. L. (2011). Gender roles: A sociological perspective (5th ed.). Pearson. 

Mayo Clinic. (2023a). Transgender facts. Mayo Foundation for Medical Education and Research. https://www.mayoclinic.org/healthy-lifestyle/adult-health/in-depth/transgender-facts/art-20044745 

Mayo Clinic. (2023b). Gender dysphoria. Mayo Foundation for Medical Education and Research. https://www.mayoclinic.org/diseases-conditions/gender-dysphoria 

Nanda, S. (1986). The hijras of India. Journal of Homosexuality, 11(3–4), 35–54. https://doi.org/10.1300/J082v11n03_03 

National Center for Transgender Equality. (n.d.). Frequently asked questions about transgender people. https://transequality.org/issues/resources/frequently-asked-questions-about-transgender-people 

Ramey, C. (n.d.). Intersex fact sheet. Accord Alliance. 

Ramey, H. L. (n.d.). Understanding gender identity. The Jed Foundation. https://jedfoundation.org/resource/understanding-gender-identity/ 

Ramey, J. B. (n.d.). SOGIE terms and tips. Chatham University Women’s Institute. 

Tannen, D. (2001). You just don’t understand: Women and men in conversation. Quill. 

Tran, N., Lunn, M., Obedin-Maliver, J., et al. (2024). Conversion practices and mental health outcomes among LGBTQIA+ people in the United States. The Lancet Psychiatry. Stanford Medicine. https://med.stanford.edu 

Yale School of Medicine. (2023). What do we mean by sex and gender? https://medicine.yale.edu/news-article/what-do-we-mean-by-sex-and-gender/ 

Bhatt, N., Cannella, J., & Gentile, J. P. (2022). Gender-affirming care for transgender patients. Psychiatry (Edgmont) / The Primary Care Companion for CNS Disorders. PMCID: PMC9341318; PMID: 35958971. 

(Tip: If you’d like, I can append your existing course bibliography—Mayo Clinic, NCTE, WPATH/Endocrine guidance—under a “Further Reading” section.) 

UCSF Gender Affirming Health Program. (n.d.-a). Transition roadmap. https://transcare.ucsf.edu/transition-roadmapTranscare UCSF 

UCSF Gender Affirming Health Program. (n.d.-b). Preoperative assessment process. https://transcare.ucsf.edu/preoperative-assessment-process Transcare UCSF 

UCSF Gender Affirming Health Program. (n.d.-c). Surgery referral assessment requirements. https://transcare.ucsf.edu/surgery-referral-assessment-requirements Transcare UCSF 

UCSF Gender Affirming Health Program. (n.d.-d). Overview of gender-affirming treatments and procedures. https://transcare.ucsf.edu/guidelines/overview Transcare UCSF 

UCSF Gender Affirming Health Program. (2016a). Initiating hormone therapy. https://transcare.ucsf.edu/guidelines/initiating-hormone-therapy Transcare UCSF 

UCSF Benioff Children’s Hospitals – Child & Adolescent Gender Center (CAGC). (n.d.). Child & Adolescent Gender Center. https://www.ucsfbenioffchildrens.org/clinics/child-and-adolescent-gender-center UCSF Benioff Children's Hospitals 

World Professional Association for Transgender Health. (2022). Standards of Care for the Health of Transgender and Gender Diverse People, Version 8. https://pmc.ncbi.nlm.nih.gov/articles/PMC9553112/ PMC