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THE TWO-SEX SYSTEM: FACT OR FALLACY?CASE STUDY FOR AAC&U STIRS PROJECTAngela Bauer, Professor and Chair of Biology, High Point University, High Point, NC STUDENT CASE IntroductionPerhaps no other method of categorization permeates our culture so thoroughly as that of classifying according to sex (biological characteristics we associate with being male or female) and/or gender (social behaviors we associate with being masculine vs. feminine). The desire to categorize in this regard is so compelling, that typically the first words out of a person’s mouth upon hearing about the birth of a child are, “Is it a boy or a girl?” Likewise, the desire to categorize as male vs. female or masculine vs. feminine is far-reaching; names, hairstyles, clothing, bathrooms, athletic events, even shampoos—all are categorized within the context of the binary male/female framework. Yet is this binary view of sex and gender accurate? Does it reflect what exists within the natural world? Can everyone be placed into one of two “boxes” (male or female) with respect to their sex and gender? And why is the impulse to categorize in this regard so strong? While it is true that at times our culture and media attempt to celebrate the concept of androgyny, most people admit to reacting with discomfort when faced with an individual or situation that defies categorization by the sex/ gender binary. Consider the case of female athlete Caster Semenya, whose sex was investigated following her gold medal win in the 800-meter dash of the 2009 World Championship:“In August 2009, Caster Semenya, a young South African runner, won the women’s 800-meter race at the Berlin World Championships in Athletics by a margin of 2.45 seconds and immediately found herself at the center of international controversy amid a frenzy of speculation about whether she was ‘really’ a woman (Clarey 2009). The controversy was sparked by complaints from Semenya’s competitors; they pointed not to the large margin of her win, but to what one writer referred to as her ‘breathtakingly butch’ appearance (Levy 2009), remarking, ‘Just look at her’ and ‘These kinds of people should not run with us . . . For me, she is not a woman. She is a man’ (Adams 2009; Levy 2009). Shortly after the media reported these comments, a supposedly misdirected fax notified the press that the IAAF had actually required Semenya to undergo ‘sex testing’ shortly before her Berlin win (Levy 2009). The IAAF had ordered South African authorities to perform the tests after Semenya broke a national junior record at the African championships in Mauritius. Throughout the testing, Semenya had been under the impression she was undergoing standard doping tests owing to her win (BBC 2009). In a moment when she might have been celebrating her victory, Semenya endured a cruel and humiliating media spectacle; sports commentators ridiculed her appearance, called her names including ‘hermaphrodite,’ and cried out for her medal and prize money to be returned (Levy 2009; A.D. Smith 2009). Under a typical headline, trumpeted ‘Could This Women’s World Champ Be a Man?’ (Adams 2009). Semenya was reportedly subjected to a two-hour examination during which doctors put her legs in stirrups and photographed her genitalia (Levy 2009; A.D. Smith 2009). Afterward Semenya sent distraught messages to friends and family (Levy 2009; A.D. Smith 2009). Test results purportedly indicated that Semenya had an intersex condition that left her without a uterus or ovaries and with undescended testes producing androgens at three times the typical level for females (known as hyperandrogenism) (Hurst 2009). [Note that Semenya’s elevated androgen levels did not confer to her any athletic advantage, due to the fact that she lacks androgen receptors to mediate the hormone’s effects.] After these intensely intimate details about Semenya’s body became a topic for public debate and scrutiny, she went into hiding; she reportedly required trauma counseling in the wake of claims that sex tests confirmed she was a ‘hermaphrodite’ (Levy 2009; A. D. Smith 2009). The IAAF banned her from competitions while it completed its investigation. Eventually, after an 11-month investigation—a process that involved 10 months of negotiation with the IAAF involving legal representatives and a high-profile mediator known for his work on international disputes—the IAAF cleared Semenya for competition and her Berlin victory was allowed to stand (Dewey and LeBoeuf 2010).” [Excerpt taken from Karzakis et al. 2014]Of note regarding Semenya’s story is the fixation of her fellow athletes, the media, and the public on her androgynous appearance (more so than on any athletic advantage her intersex condition may have conferred; Karzakis et al. 2014). Significant discomfort (in some cases, ridicule) was elicited by her appearance, which didn’t fit neatly within the sex/gender binary. There existed so much discomfort in this regard that Semenya was actually pressured into having significant medical procedures performed to “feminize” her appearance, including surgery to reduce the size of her clitoris. Clitoral reduction surgery is a risky and complicated medical procedure, conducted for the sake of feminizing appearance. Furthermore, the surgery can cause scarring, pain, and numbness in the vulva, resulting in long-term impairment of one’s sexual response (Crouch et al. 2007; Piaggio 2014). In short, it is a surgery that is performed for the benefit of upholding the sex/gender binary, and not for the sexual health of the individual. And yet it is still a surgery that is widely used within the medical community to “treat” intersex individuals like Semenya (Fausto-Sterling 2000; Romao et al. 2012; Piaggio 2014).In this case study, you will engage in readings and activities that encourage you to consider the validity of society’s two-sex system. In addition to learning about the biologic factors that contribute to sexual phenotype (male, female, intersex), you will examine data sets that illustrate the significant variability in expression of secondary sex characteristics that exists within the natural world. You will consider the role that scientific texts have played in perpetuating the formation of the sex/gender binary. Finally, you will engage in debates with your peers, during which you will formulate arguments that are either in favor of or against the application of binary views and language pertaining to sex and gender on college campuses, particularly when making decisions pertaining to campus housing.Specific learning objectives for the case study—as well as the activities and assignments included to address each objective—include:Learning ObjectiveRelated Activities/Assignments1. To explain the biology of sexual development and the contributions of six key factors—chromosomes, gonads, hormones, external genitalia, internal genitalia, and secondary sex characteristics —to sexual phenotypeUnit OneReading assignment: “The Biology of Sex” (contained in this document)Designing a “Determinants of Sexual Phenotype” flowchart 2. To explain the causes of intersex conditions, their prevalence within the human population, and common approaches used within the medical community to “treat” themUnit TwoReading assignments: “Intersex Conditions: Causes, Prevalence, and the Medical Community’s Response” (contained in this document); “What If It’s (Sort of) a Boy and (Sort of) a Girl?,” completion of the “Predicting Sexual Phenotype” activity Viewing of “Hermaphrodites Speak,” . To analyze and interpret data sets illustrating variability in expression of common secondary sex characteristics Unit ThreeIn-class completion of “Distinct or Overlapping Populations?” Learning Objectives, cont’d.Related Activities/Assignments4. To evaluate the experiences of intersex individuals, in order to identify the challenges they face within the context of society’s two- sex systemUnit FourReading assignments: “A New Era for Intersex Rights,” ; “In Amerika They Call Us Intersex,” ; “A Girl Named Steve,” ; optional Pulitzer Prize-winning novel Middlesex, by Jeffrey EugenidesUnit Four discussion questions5. To describe how scientific texts have contributed to the perpetuation of the two-sex systemActivities and readings included in Units One to Three6. To formulate an argument that either defends or argues against application of the two-sex system on college campusesUnit FiveIn-class completion of a debate: “The Sex/Gender Continuum and The College Dorm”Unit One: The Biology of SexSuggested Supplemental ReadingsFausto-Sterling, A. 2012. Sex/Gender—Biology in a Social World [Chapter Three]. New York: Routledge.Jones, R. E., and K. H. Lopez. 2006. Human Reproductive Biology, 3rd edition [Chapter Five]. San Diego: Academic Press. Sex is often discussed—particularly in traditional science textbooks—as being a relatively straightforward issue, with clear categories of male and female. Yet a closer examination of sexual phenotype (observable characteristics)—particularly in the case of intersex individuals like Semenya—reveals that the physical expression of sex is much more complex. In reality, sexual phenotype is comprised of six different markers, and none of these is strictly binary. These markers include chromosomes, gonads, hormones, internal genitalia, external genitalia, and secondary sex characteristics. The role of each of these markers in contributing to sexual phenotype is the focus of Unit One of this case study. Of note is the fact that prior to masculinization or feminization of reproductive structures during human development, all embryos—regardless of sexual genotype (genetic makeup of an individual)—possess a neutral phenotype. In other words, the physical structures that initially comprise the reproductive system are identical, and include gonads (indifferent gonads or gonadal ridges) that are neither ovary- or testes-like, a set of internal tubes (the Mullerian ducts and Wolffian ducts) that in no way represent (but have the potential to form) masculine or feminine structures, and a collection of external tissues (including a phallus) that is undifferentiated (in other words, neither penis- nor clitoris-like). These neutral tissues—and the structures that they have the potential to form, depending on chromosomal and hormonal influences —are depicted in Figures 1 and 2 and summarized in Table 1.Figure 1. Development of Gonads and Internal Reproductive Structures[OpenStax College - Anatomy & Physiology, Connexions Web site. , Jun 19, 2013] Figure 2. Development of the External Genitalia*[Human Physiology, , 2011.]*Note that the perineum is the entire region that surrounds and includes all of the structures pictured above.Table 1. Potential Contributions of Embryonic Reproductive Structures to Sexual PhenotypeEmbryonic StructurePotential TriggerKey Factor(s) Influencing Differentiationgonadal ridgesGenesIf SRY gene is present and Rspo1 is absent/inhibited then, testes formIf Rspo1 is present and SRY gene is absent, then ovaries form Mullerian DuctsAnti-Mullerian Factor (AMF)If AMF and receptors are present, Mullerian ducts degenerate. If AMF or its receptors are absent, Mullerian ducts differentiate into oviducts, uterus, cervix, and the upper one-third of vaginaWolffian DuctsTestosteroneIf testosterone and its receptors are present, Wolffian ducts develop into epididymis, vas deferens, and seminal vesicles If testosterone or its receptors are absent, Wolffian ducts degenerategenital tubercle, urogenital folds, and labioscrotal swellings Dihydrotestosterone (DHT, produced by action of 5?-reductase on testosterone)If DHT and its receptors are present the glans (head) of penis enlarges, the urogenital folds fuse along perineal raphe to form shaft of penis, and the labioscrotal swellings form the scrotum In the absence of androgens and, possibly, the presence of estrogen, growth of the genital tubercle is limited and becomes the clitoris, urogenital folds become labia minora, and labioscrotal swellings become labiaSix Markers of Sexual PhenotypeChromosomes[For a review of chromosomes, DNA, and genes, visit this link: .] While much remains to be discovered regarding the genetic controls of sexual differentiation, two genes in particular seem to play key roles in pushing the process in either a masculine or feminine direction. These two genes are the SRY gene (the “sex determining region on the Y chromosome”) and the R-spondin gene (referred to as Rspo1 and found on chromosome 1). Both play a role in directing the maturation of the neutral gonads (the first step in sexual development). Rspo1 plays a key role in directing the neutral gonads to form ovaries in embryos that have an XX (female) genotype. When the SRY gene is present (in other words, in embryos that have an XY or male genotype), SRY inhibits Rspo1, thereby causing the neutral gonads to form testes. Recent research indicates that humans can develop testes for gonads even with an XX genotype (in other words, even with no Y chromosome or SRY gene) if they lack Rspo1 activity. In such cases, genetic testing reveals a feminine genotype (XX) in individuals that have a masculinized phenotype.Gonads and HormonesOnce the aforementioned genes (Rspo1, SRY) orchestrate gonadal differentiation, the mature gonads (ovaries or testes) then produce hormones that direct the differentiation of other reproductive structures (the internal and external genitalia). In XX embryos, the neutral gonads differentiate into ovaries between weeks eight through twelve. It is the estrogen (female sex hormone) produced by these ovaries—as well as estrogen produced first by the mother that causes the internal and external genitalia to feminize (as is described in the next section). In XY embryos (in other words, when SRY is present and inhibits Rspo1 activity), the neutral gonads form testes typically by week eight. These testes then produce two key hormones that play a role in directing the internal and external genitalia to masculinize. These two key hormones are testosterone (an androgen, or male sex hormone) and Anti-Mullerian Factor (AMF; this hormone is also referred to as Mullerian Inhibiting Substance, or MIS).An important caveat to the success of hormonal activity is the availability of receptors to mediate hormone actions. As Figure 3 illustrates, hormones exert effects on target cells only when they can bind to their receptors (found either on the surface of cells or inside cells). It is the hormone-receptor complex then that is able to alter the activities of a cell/tissue /organ. If an individual lacks the appropriate receptor(s) for a given hormone, that hormone—regardless of how much of it is present—will be unable to exert changes within the body.Figure 3. Hormones Exert Effects on Cells/Tissues/Organs by Acting through their ReceptorsInternal GenitaliaOnce the neutral gonads have developed into ovaries or testes, the hormones produced by the gonads then act to establish internal reproductive sex. In other words, they activate their receptors on the Wolffian ducts and/or Mullerian ducts to cause the formation of masculine or feminine internal genitalia, respectively (listed in Table 1 and illustrated in Figure 1). If testes have formed from the neutral gonadal ridges, the AMF that they produce will cause the Mullerian ducts to self-destruct, thereby eliminating the developmental option of feminized internal reproductive structures. Testosterone— also produced by the testes—will then act on the Wolffian ducts and cause them to form male internal genitalia (vas deferens, seminal vesicles, and epididymis). Conversely, if ovaries have formed from the neutral gonadal ridges, the Wolffian ducts degenerate. This is thought to be due to the absence of appreciable levels of testosterone or other androgens in embryos with feminized gonads. The Mullerian ducts then partially fuse and differentiate into female internal genitalia (fallopian tubes, uterus, cervix, and the upper one-third of the vagina). The process of Mullerian duct differentiation is thought to be stimulated by estrogen (coming first from the mother and then from the differentiated embryonic ovaries). External GenitaliaAt around the same time that gonadal hormones direct differentiation of internal reproductive structures, they begin to do the same to external reproductive structures. In their undifferentiated or neutral state, the external genitalia consist of a phallus (the genital tubercle), genital folds, and genital swellings (see Figure 2 and Table 1). If the external genitalia are to masculinize (in other words, if they are to form a penis or a scrotum), they must be acted upon by androgens (the male sex hormones). In order for androgens to masculinize the external genitalia, not only must androgen receptors be present, but testosterone (the primary type of androgen made by the testes) must be converted to a more physiologically active version of androgen called dihydrotestosterone (DHT). DHT is produced from testosterone due to the actions of the enzyme called 5-?-reductase, which is present in cells of the undifferentiated external genitalia. When DHT is produced, it acts via androgen receptors (the same ones that mediate testosterone actions) to cause the labioscrotal (genital) swellings to fuse along the midline and form the scrotum, the urethral (genital) folds to fuse to form the shaft of the penis, and the genital tubercle to form the tip of the penis (depicted in Figure 2). The extent of virilization (including phallus length) can vary quite significantly and is correlated with androgen concentration and sensitivity.Two factors seem to account for the feminization of the external genitalia in embryos that have ovaries for gonads. These factors include 1) the relative lack of gonadal androgens (which eliminates virilization of the external genitalia as an option; while the embryonic ovaries can produce some androgens, levels are minimal); and 2) the presence of estrogens. Since the mechanisms accounting for feminization of the external genitalia have not been studied as extensively as the process whereby the genitalia are masculinized, our understanding of the role that estrogen plays in the process of feminization is underdeveloped. Nonetheless, when these conditions are present, the genital tubercle forms a clitoris, the genital folds become the labia minora (the small labia of the vulva), and the genital swellings become the labia majora (the large labia of the vulva; see Figure 2 and Table 1). Secondary Sex CharacteristicsPhysical characteristics (other than reproductive structures) that we associate with being masculine or feminine are referred to as secondary sex characteristics. These characteristics appear most prominently at the time of puberty, when the gonads begin to secrete significant quantities of the sex hormones (androgens and estrogens). While both types of gonads (ovaries and testes) produce both types of sex hormones, the testes produce significantly higher levels of androgens than estrogens, and the ovaries produce greater levels of estrogens than androgens. It is the difference in the ratio of sex hormones that accounts for the expression of masculine vs. feminine secondary sex characteristics. When estrogen concentrations predominate in the bloodstream, female secondary sex characteristics are expressed. Some examples include breast development, deposition of fat in a female-specific pattern (in the region of the hips and buttocks), and widening of the pelvis. When androgen concentrations predominate in the bloodstream, male secondary sex characteristics are expressed. Examples of these masculine characteristics include facial hair growth, heavier skull and bone structure, and lengthening of the vocal folds of the larynx (which causes deepening of the voice). As Unit 3 of this case study will highlight, the expression of secondary sex characteristics is highly variable and correlates with levels of and sensitivity to sex hormones.Unit One Activity: Developing a “Determinants of Sexual Phenotype” FlowchartIn order to review, visualize, and summarize the process of sexual development, design a flowchart that has incorporated into it the six markers of sexual phenotype (chromosomes, gonads, hormones, internal genitalia, external genitalia, and secondary sex characteristics). Keep the following elements of design in mind as you construct your flowchart:a processing step is denoted with a rectangular box; anda decision is denoted with a diamond.See Figure 4 for an example starting point for your “Determinants of Sexual Phenotype” flowchart. Keep the flowchart handy for future reference, particularly when engaging in Unit Two’s activity (“Predicting Sexual Phenotype”)Figure 4. Suggested Beginning for a “Determinants of Sexual Phenotype” FlowchartUnit Two: Intersex Conditions: Causes, Prevalence, and the Medical Community’s ResponseCausesAs you learned in Unit One, a variety of different markers contribute to sexual phenotype. While scientific texts typically portray sexual development as a binary phenomenon (with all markers in a given individual being congruent—either feminine or masculine), a survey of the natural world reveals much greater complexity in the expression of sexual phenotype. Not only are the markers of sex not necessarily congruent within a given individual (resulting in intersex phenotypes, the focus of this unit), but there is also great variability in the expression of a particular marker (e.g., sex hormone levels) among individuals in whom all markers are congruent, and who “fit” within the sex/gender binary (the focus of Unit Three of this case study). So what does it mean to be intersex? A variety of definitions exist for the term intersex, ranging from those that convey acceptance of natural variation in the expression of sex (e.g., a sexual phenotype that doesn't fit the classic definitions of male or female or a unique physical state) to those that are medicalized and suggest the need or desire to “treat” or “fix” (e.g., “a disorder of sexual development” or DSD; Feder and Karzakis 2008). In the past, intersex individuals were referred to as hermaphrodites, and were divided into two categories: true hermaphrodites and pseudohermaphrodites. True hermaphrodites are individuals whose intersex state is due to genetic mosaicism (with some cells being XX and others XY). Pseudohermaphrodites, on the other hand, are individuals who have a genotype that is consistent from cell to cell (XX or XY, for example) but who have an individual gene (or chromosome) difference that alters the pathway of sexual differentiation. As a result, pseudohermaphrodites have both masculine and feminine characteristics.[Note that while this case study uses the term intersex to refer to individuals whose sexual phenotype doesn’t meet the classic definition of male or female, members of the medical community, psychologists, and advocacy groups have recently agreed to uniformly use the term DSD (“disorder of sexual development”) to refer to intersex states (Romao et al. 2012). This controversial decision will be a topic of discussion later in this case study.]Intersex states don’t fit neatly within the sex/gender binary, typically (but not always) due to the fact that some aspect of sexual phenotype isn’t congruent with sexual genotype. Consider the case of Caster Semenya, whose story is highlighted in the introduction to this case study. Semenya is intersex due to a condition known as androgen insensitivity syndrome or AIS. Intersex individuals like Semenya have an XY (masculine) genotype, and their sexual development proceeds through the initial steps of masculinization that were described in Unit One of this case study: namely, the SRY gene (present on the Y chromosome) suppresses Rspo1, which causes the neutral gonads to form testes. The testes then produce testosterone and AMF, as expected. While AMF is able to cause degeneration of the Mullerian ducts, testosterone (and DHT) are unable to fully act within the body due to the fact that individuals with AIS are either completely insensitive to androgen actions (due to a total lack of functional androgen receptors) or partially insensitive (due to a partial deficit in functional receptors). Thus, androgens are unable to fully masculinize the Wolffian ducts and external genitalia. As a result, individuals with AIS have the intersex phenotype described in Table 2, and certain aspects of their sexual phenotype are incongruent with sexual genotype.Table 2. Phenotype of Intersex Individuals with Complete or Partial Androgen Insensitivity Syndrome (AIS)Marker of SexDifferentiated PhenotypeChromosomesXY (masculine)Gonadstestes (masculine)Hormonestestosterone, AMF, DHT (masculine)Internal GenitaliaMullerian ducts degenerate; Wolffian ducts either completely degenerate (with complete AIS, or CAIS) or partially develop (with partial AIS, or PAIS)External Genitaliavulva and vaginal opening (feminized) with CAIS; ambiguous (partially masculinized) with PAISSecondary Sex Characteristicsfeminized (with CAIS); partially masculinized (with PAIS) [For an animation of sexual development in embryos with CAIS and PAIS, see . ]IncidenceCAIS and PAIS are just two of many intersex states that exist within the human population (see Table 3 for other examples). Accurate statistics regarding the frequency of occurrence of intersex states are difficult to obtain, for three distinct reasons: 1) there is much secrecy and shame surrounding the topic, causing intersex individuals and their families to hide their phenotype; 2) some examples of intersex states are undetectable without in-depth medical examination (and thus go undetected); and 3) there are no concrete guidelines for the definition of intersex. Nonetheless, of those statistical analyses that have been conducted, estimates for the incidence of intersex states range from 1 in 2,000 births to 1.7 per 100 births (Blackless et al. 2000). When reviewing Table 3, note the relative frequency of intersex states vs. other unique phenotypes (e.g., red hair) within the human population.Table 3. Estimated Frequency of Intersex* and Other Phenotypes in the Human PopulationPhenotypeEstimated Frequency/100 Live BirthsNon-XX or non-XY (except Turner or Klinefelter)0.0639Turner Syndrome0.0369Klinefelter Syndrome0.0922Complete Androgen Insensitivity Syndrome0.00760Partial Androgen Insensitivity Syndrome0.000760Classic Congenital Adrenal Hyperplasia (CAH)0.00770Late Onset CAH1.5Vaginal Agenesis0.0169True Hermaphrodites0.0012Idiopathic (unknown origin)0.0009Red hair**1–2Green eyes***2Albinism****0.00005882Males with height > 6’7”0.05Females with height > 6’1”0.05* Blackwell et al. 2000**Garreau 2002*** Sturm and Frudakis 2004****Gronskov et al. 2007Medical Community’s ResponseTypically, one of the first questions asked of new parents is, “Is your baby a boy or a girl?” This question can create a great deal of anxiety for parents of a newborn whose reproductive phenotype does not fit within the two-sex system. They envision the challenges that their child will face as they try to navigate a society that is entirely structured around a binary view of sex and gender (e.g., public restrooms, gym classes, college roommate assignments) and fear the social ostracism that will result if their child doesn’t fit in. In order to prevent their child the anguish of marginalization due to their intersex state, they—in consultation with their physician(s)—often take significant medical steps to help their child assimilate. When addressing intersex states in which the external genitalia are “ambiguous” (neither masculine nor feminine), the traditional approach of the medical community has been to strongly urge parents to choose a gender identity (male or female) for their child as soon as possible after birth. This is typically done in consultation with medical professionals, taking factors such as chromosomal sex, genital appearance, surgical options, potential for fertility, views of the family, and sometimes circumstances relating to cultural practices into consideration (Lee et al. 2006; Romao et al. 2012). After a sex is chosen, the medical team typically follows up with surgery (usually several surgeries over the span of years) to align the genitalia with the chosen sex. Given that surgically feminizing the genitalia is more easily accomplished than masculinizing the genitalia, sex assignment of intersex newborns has traditionally been skewed in the direction of feminization. While the physicians and parents who employ this traditional, medicalized approach to treating intersex conditions are well intentioned and certainly mean no harm, many intersex individuals who have undergone “normalizing” surgery report that the experience was damaging to both their emotional and sexual well being. From an emotional standpoint, intersex individuals report feeling traumatized by repeatedly having their genitals on “medical display,” as doctors, nurses, and medical students, examine, touch, and photograph them. The serial surgeries and post-op treatments involved with “normalizing” the genitalia can be painful and confusing for children. Proper healing of a surgically created vagina, for example, requires daily dilation with a hard instrument for months in order to prevent the vagina from closing up. Beyond the potential for emotional trauma, “normalizing” surgeries also have the potential to cause long-term damage to the sexual response. In particular, clitoral reduction surgery (clitoroplasty, as is often performed to feminize external genitalia that has been partially or fully masculinized during sexual development) can leave scar tissue and/or nerve damage that permanently reduces sensation and thereby interferes with the sexual response (Crouch et al. 2007; Piaggio 2014). While new surgical procedures are being developed and implemented in the hopes of minimizing the loss of sensation associated with clitoroplasty, the surgical community acknowledges that “no surgery will be less damaging [to clitoral sensation] than the best possible operation performed in a center of excellence” (Piaggio 2014). Listening to the firsthand accounts of intersex individuals is particularly helpful for understanding the negative effects (both physical and emotional) that can potentially result from medical treatment of intersex conditions. Such firsthand accounts are available in the film “Hermaphrodites Speak” (viewed within this unit of the case study) and will also be reviewed and discussed later in Unit Four. Unit Two Reading and Viewing AssignmentsWeil, E. “What if It’s (Sort of) a Boy and (Sort of) a Girl?” New York Times, September 24, 2006, Society of North America. 1996. “Hermaphrodites Speak,” YouTube video, 34:59, Two Activity: Predicting Sexual PhenotypeUse the flowchart developed during the Unit One activity to guide your reasoning as you predict the sexual phenotype of the following intersex states. Intersex StateDescriptionChromosomesHormones(androgens, estrogens, AMF?)Gonads(ovaries, testes)Internal genitaliaExternal genitaliaComplete Androgen Insensitivity Syndromeno functional androgen receptors are present (androgen insensitive)XYPartial Androgen Insensitivity Syndromereduced number or sensitivity of androgen receptorsXYCongenital Adrenal Hyperplasiaadrenal glands produce high levels of androgensXX5?-ReductaseDeficiency(“Guevedoces”)lacks enzyme that converts testosterone to DHTXYUnit Three: Secondary Sex Characteristics: Binary or Continuum?The phenotypes and experiences of intersex individuals (in whom not all markers of sex are congruent; addressed in Units Two and Four of this case study) call into question the adequacy of the two-sex system for capturing the variability that exists with respect to sex states in the natural world. The limitations of the system are also called into question when examining variability in the expression of a particular marker of sex (e.g., sex hormone levels) among individuals in whom all markers are congruent, and who theoretically “fit” within the sex/gender binary. While the two-sex system perpetuates the notion that sex differences in a given characteristic are obviously binary (masculine vs. feminine), a closer examination of the data—like the one you will conduct during Unit Three’s activity, “Distinct or Overlapping Populations?”—indicates that this is not always the case.Unit Three Activity: Distinct or Overlapping Populations?Part One: Examine the data illustrated in Tables 4 through 6. Then, answer the following questions:1.Select testosterone data from three of the methods of detection depicted in Table 4. Then, for each of the methods of testosterone measurement, construct a bar graph that illustrates the following: the mean levels + SD of testosterone detected in males vs. females; the median levels + SD of testosterone detected in males vs. females; and the range of testosterone levels depicted in each sex.2.Are the data obtained from the various methods of detection equivalent, or is there variability in levels of testosterone detected from method to method? If variability exists, what might this mean for cross-study comparisons of testosterone levels?3.Are the sex-specific ranges of testosterone levels distinct or overlapping within each method?4.If you were provided with a serum sample for testosterone measurement in an individual of unknown sex, would you be able to predict their sex based on the level of testosterone you measured? Explain.5.Using data illustrated in Tables 5 and 6, determine the following: mean lengths of the adult clitoris and penis; mean volumes of the adult clitoris and penis; and the range of phallus lengths identified in each sex.6.Do the ranges for phallus length (of the clitoris, penis) overlap? If not, how close do they come to overlapping?7.Discuss your impressions regarding the range of penis and clitoris lengths depicted in Tables 5 and 6. Are the lengths more or less variable than what you would have predicted?Part Two: Height is often cited as a sexually dimorphic characteristic, with males being taller, on average, than females. In order to examine the variability that exists within and between the sexes with respect to height, conduct the following experiment:8.While working in pairs, measure the height of each individual in the class. It is important to precisely measure each individual’s height (rather than relying on each individual to report their own height) since inaccuracies can result with self-reporting. Each individual should anonymously write their measured height on a piece of paper, along with the sex/gender they most closely identify with in their day-to-day life. Collect the slips of paper, and identify two students who will then enter the data into an excel spreadsheet.9.Post the data spreadsheet where it can be accessed by the entire class. Then, work in pairs to calculate the following with respect to class measurements: the mean height + SD of the class, of the females, and of the males; the median height of the class, of the females, and of the males; and the ranges of heights observed in the class, in females and in males. Conduct a t test to determine if the difference in mean height observed between the sexes is statistically significant. Graph your results.10.Discuss the results of your analyses. Were the ranges of heights observed in the two sexes overlapping? Were the mean differences in heights observed between the sexes statistically significant? If you were to know the height of an individual, would you be able to predict their sex based on this informatioTable 4. Testosterone Values in Men and Women Obtained from 10 Different Methods of MeasurementID/GC-MSArchitect i2000ACS-180Immuno-1VidasImmulite 2000Vitros ECiAutoDelfiaElecsys 2010RIA ImmunotechCoat-A-Count DPCMen (n = 50)?Samples, n5045505050505050505050?Median, nmol/L19.520.323.020.615.916.316.022.315.916.520.5?Mean, nmol/L21.219.523.721.716.518.817.821.916.417.020.7?SD, nmol/L10.87.311.211.28.29.710.09.08.89.39.3?Range, nmol/L8.2–57.65.5–38.88.6–69.45.5–68.23.0–38.56.2–53.44.5–56.77.6–54.43.4–49.62.9–45.86.2–52.7Women (n = 55)?Samples, n5554555551535555535451?Median, nmol/L2.13.14.02.51.75.02.04.91.22.52.6?Mean, nmol/L2.23.54.32.82.25.52.25.11.62.72.8?SD, nmol/L1.21.93.01.61.83.31.42.61.31.41.6?Range, nmol/L0.6–7.20.8–11.71.7–16.20.2–8.80.4–10.90.9–18.40.2–8.50.1–13.80.2–7.60.4–9.00.7–9.4Taieb, J., B. Mathian, F. Millot, M. C. Patricot, E. Mathieu, N. Queyrel, I. Lacroix, C. Somma-Delpero, and P. Boudou. 2003. “Testosterone Measured by 10 Immunoassays and by Isotope-Dilution Gas Chromatography–Mass Spectrometry in Sera from 116 Men, Women, and Children.” Clinical Chemistry, 49(8): 1381–1395 (Adapted from Table 1, with permission from the American Association for Clinical Chemistry).Table 5. Measurements of Adult Female Genitalia (n=50)?Mean [SD]RangeClitoral length (mm)19.1 + 8.75–35Clitoral glans width (mm)5.5 + 1.73–10Clitoris to urethra (mm)28.5 + 7.116–45Labia majora length (cm)9.3 + 1.37.0–12.0Labia minora length (mm)60.6 + 17.220–100Labia minora width (mm)21.8 + 9.47–50Perineum length (mm)31.3 + 8.515–55Vaginal length (cm)9.6 + 1.56.5–12.5Tanner stage (n)IV4V46Colour of genital area compared with surrounding skin (n)Same9Darker41Rugosity of labia (n)Smooth14Moderate34Marked2Reprinted from Lloyd, J., N. S. Crouch, C. L. Minto, L- M. Liao, and S. M. Creighton. 2004. “Female Genital Appearance: ‘Normality’ Unfolds.” International Journal of Obstetrics and Gynecology, 112: 643–646. Copyright ? 2004, John Wiley and Sons.Table 6. Measurements of Adult Male GenitaliaMean + SDRangePenile shaft length (cm)7.76 + 1.35.5–12Penile shaft volume (cm3)46.5 + 17.220–97Glans penis length (cm)4.4 + 0.43.5–5.5Total penis length (cm)12.18 + 1.79–17.5Reprinted from Spyropoulos, E., Borousas, D., Mavrikos, S., Dellis, A., Bourounis, M., and S. Athanasiadis. 2002. “Size of External Genital Organs and Somatometric Parameters among Physically Normal Men Younger than 40 Years of Age.” Urology, 60(3): 485–489. Copyright 2002, Elsevier. Unit Four: The Experiences of Intersex Individuals in a Binary WorldIn Unit Four, you will read the firsthand accounts of individuals who are intersex and navigating life within a binary world. These “anecdotal” accounts constitute a different type of evidence than is typically sought in biological science contexts. From a social science and policy perspective, however, these authentic voices provide a bridge for society to understand the negative repercussions of standard medical approaches to “treating” intersex states.As you read these narratives, make note of the unique challenges intersex individuals face within the context of society’s two-sex system. Then, during class, work within small discussion groups to answer the questions posed below.Reading AssignmentsGreenhouse, E. “A New Era for Intersex Rights,” New Yorker, December 2013, , L. S. “A Girl Named Steve,” Libido—The Journal of Sex and Sensibility, Retrieved June 9, 2014, , A. “In Amerika They Call Us Intersex,” Libido—The Journal of Sex and Sensibility, Retrieved June 9, 2014, , J. 2002. Middlesex. New York: Picador Paperback.Unit Four Discussion QuestionsPick two of the individuals highlighted in the readings and describe their reproductive phenotype. What is the biological basis of their intersex state? What aspects of their phenotype don’t allow them to “fit” within society’s two-sex system?Are there social challenges that these intersex individuals share in common? What are the challenges most frequently cited in these narratives?Based on the experiences of intersex individuals that were shared in the readings, what recommendations would you make to the parents of intersex children to eliminate (or lessen the severity of) these challenges? To physicians?Discuss the pros and cons of genital normalization surgeries/ procedures. Can you envision a world in which intersex states are as readily accepted as being male or female? Why or why not?Discuss the implications of labeling intersex phenotypes as “disorders of sexual development.” Unit Five: A Debate—“The Sex/Gender Continuum and The College Dorm”While many college campuses organize student housing along the binary of sex/ gender, some are beginning to address the inadequacy of sexed housing, since it fails to be a comfortable or safe environment for students who don't fit within the binary (e.g., intersex students). Yet offering gender neutral housing on college campuses has not come without controversy, with some arguing that it will promote sexual promiscuity and create a distracting environment, among other things (see Unit Five, you will work to formulate a case that either argues for or against gender neutral housing on college campuses. Prior to coming to class on the day on which the debate will take place, the class will be divided into teams of five. Work with your team to prepare written briefs on both sides of the issue, and come to class prepared to argue either side. On the day of the debate, your team will be matched up against another team in the class. Just before the debate, flip a coin to see which side your team will represent, and select an individual from your team to start the debate against another team. The debate itself will start with the pro side (in defense of gender neutral housing) presenting for five minutes. Then a person representing the con side (from the other team) will speak for five minutes. There is a five-minute rebuttal by a second speaker on the pro side, followed by a five-minute rebuttal on the con side. This is then followed by three-minute summaries by each side. Questions from the audience will be permitted in order to evaluate the content and presentation of the debate.ReferencesBlackwell, M., A. Charuvastra, A. Derryck, A. Fausto-Sterling, K. Lauzanne, and E. Lee. 2000. “How Sexually Dimorphic Are We? Review and Synthesis.” American Journal of Human Biology, 12: 151–166.Crouch, N. S., L- M. Liao, C. R. J. Woddhouse, G. S. Conway, and S. M. Creighton. 2007. “Sexual Function and Genital Sensitivity Following Female Genitoplasty for Congenital Adrenal Hyperplasia.” Journal of Urology, 179(2): 634–638.Eugenides, J. 2002. Middlesex. New York: Picador Paperback.Fausto-Sterling, A. 2000. Sexing the Body: Gender Politics and the Construction of Sexuality. New York: Basic Books.———. 2012. Sex/Gender—Biology in a Social World. New York: Routledge.Feder, E. K., and K. Karzakis. 2008. “What’s in a Name? The Controversy Over ‘Disorders of Sexual Development.’” The Hastings Center Report, 38(5): 33–36. Garreau, J. "Red Alert!," Washington Post, March 18, 2002, , E. “A New Era for Intersex Rights,” New Yorker, December 2013, , K., J. Ek, and K. Brondum-Nielsen. “Oculocutaneous Albinism.” Orphanet Journal of Rare Diseases, November 2, 2007, . Intersex Society of North America. 1996. “Hermaphrodites Speak,” YouTube video, 34:59, , R. E., and K. H. Lopez. 2006. Human Reproductive Biology, 3rd edition. San Diego: Academic Press.Karzakis, K., and R. Jordan-Young. 2014. “The Trouble With Too Much T.” New York Times, April 11, 2014, .Karzakis, K., R. Jordan-Young, G. Davis, and S. Camporesi. 2014. “Out of Bounds? A Critique of the New Policies on Hyperandrogenism in Elite Female Athletes.” American Journal of Bioethics, 12(7): 3–16.Lloyd, J., N. S. Crouch, C. L. Minto, L- M Liao, and S. M. Creighton. 2005. “Female Genital Appearance: ‘Normality’ Unfolds.” International Journal of Obstetrics and Gynecology, 112: 643–646.Long, L. S. “A Girl Named Steve.” Libido—The Journal of Sex and Sensibility, Retrieved June 9, 2014, , A. “In Amerika They Call Us Intersex.” Libido—The Journal of Sex and Sensibility, Retrieved June 9, 2014, Link! OpenStax College Anatomy and Physiology, Connexions Web site. 2013. 2915—Sexual Differentiation, , L.A. 2014. “Congenital Adrenal Hyperplasia: Review from a Surgeon’s Perspective in the Beginning of the Twenty-first Century.” Frontiers in Pediatrics, 1(50): 1–7. Romao, R. L., J. L. Salle, and D. K. Wherrett. 2012. “Update on the Management of Disorders of Sexual Development.” Pediatr Clin North Am, 59(4): 853–869.Spyropoulos, E., D. Borousas, S. Mavrikos, A. Dellis, M. Bourounis, and S. Athanasiadis. 2002. “Size of External Genital Organs and Somatometric Parameters among Physically Normal Men Younger than 40 Years of Age.” Urology, 60(3): 485–489.Sturm, R. A., and T. N. Frudakis. 2004. “Eye Colour: Portals into Pigmentation Genes and Ancestry.” Trends in Genetics, 20: 327–332.Svitek, P. “George Mason University to Offer Gender-Neutral Housing in Fall 2014.” Washington Post, February 16, 2014, , J., B. Mathian, F. Millot, M. C. Patricot, E. Mathieu, N. Queyrel, I. Lacroix, C. Somma-Delpero, and P. Boudou. 2003. “Testosterone Measured by 10 Immunoassays and by Isotope-Dilution Gas Chromatography–Mass Spectrometry in Sera from 116 Men, Women, and Children.” Clinical Chemistry, 49(8): 1381–1395.Weil, E. “What if It’s (Sort of) a Boy and (Sort of) a Girl?” New York Times, September 24, 2006, . 2011. Human Physiology, the AuthorAngela Bauer recently assumed the position of professor and chair of biology at High Point University, after spending sixteen years within the University of Wisconsin (UW) System, where she served as chair of human biology and special assistant to the provost (Institutional Assessment) at UW–Green Bay. In addition to conducting scientific research on the negative health effects of exposure to environmental endocrine disruptors, she also conducts research in the field of the Scholarship of Teaching and Learning (SoTL). Her specific SoTL interests include the impact of active learning strategies on academic performance and engagement within the science classroom (in both general education courses for non-majors and upper-level courses for majors), the benefits of the flipped classroom for providing opportunities that foster deep disciplinary learning within the sciences, and inclusive classroom practices that close the opportunity gap between majority and underrepresented students in the sciences. For her work on successfully closing the opportunity gap in an introductory biology course at UW–Green Bay, she was awarded the UW System Board of Regents Diversity Award (Individual Category) in February 2013. Both at UW–Green Bay and now at High Point University, she has served as co-director of a Teaching Scholars Program, which engages faculty in yearlong SoTL projects designed to foster teaching innovation and gather evidence regarding the impact of specific classroom strategies on student performance. ................
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