Are there records of monozygotic twins in which one experiences androgen insensitivity syndrome

Are there records of monozygotic twins in which one experiences androgen insensitivity syndrome

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I have given my high school biology students the thought experiment of "What would happen if a researcher induced twinning of a female zygote and then replaced one of the X Chromosomes with a copy of the father's Y chromosome". In theory you should get what would be about as close as possible to male/female identical (monozygotic twins). However, I don't believe it would be possible for this to occur in nature (feel free to correct this if I am wrong). The closest I am familiar with is "Semi-identical twins in which the egg is fertilized by two sperm and then twinning occurs. However this isn't really the same. However, I realized that Androgen Insensitivity Syndrome, in which a mutation leads to the body not responding to masculinizing hormones, leads to a male developing as female. Is anyone aware of this ever happening? I realize it would need to occur after the zyote/morula split.

Similarly if the SRY gene (essentially the master control switch for masculinizing an embryo) has ever been transferred on to an early embryo of a pair of female monozygotic twins, essentially inducing one twin to develop male.

In essence I'm asking for evidence of physical manifestations of (near)identical monozygotic twins. Has any of this ever been done in research on other species?

This is an important question to geneticists because monozygotic twins are the only ethically acceptable way to research genetically identical humans.

I'm sure the sort of non-symmetrical fission where specific DNA coding for genes are not present or are modified to completely different phenotype in the formation of the twins probably has happened, but it incredibly rare. In stem cells, asymmetric division has been observed frequently (warning: google doesn't like PlosOne right now). In development, unless its actively been activated as an asymmetric division, this would be incredibly rare- this would be akin to a birth defect in a single fetus - how many cases of mixed male and female cells in a single baby. I can't even find a reference for such a thing. Much more common are semi-identical twins, where two different sperm fertilize a single egg which may have split. Semi-twins are still vanishingly rare - the first report was in 2007).

Such twins are probably very rare. Their existence and discovery relies on three unusual, and possibly unlinked, events: first, that an egg fertilized by two sperm develops into a viable embryo; second, that this embryo splits to form twins; and third, that the children come to the attention of science.

This might be the case you are thinking of? In one case reported there was a gender difference.

Souter and her colleagues investigated the twins' genetic makeup because one was born with ambiguous genitalia. This twin turned out to be a 'true hermaphrodite', with both ovarian and testicular tissue. The other twin is anatomically male.

They weren't monozygotic though. Just others from the same mother ;)

Monozygotic twins are not completely identical, epigenetic fingerprinting - including DNA methylation and chromatin DNA binding patterns (pnas - paywall) change while the fetus develops and as the child and adult age. This can cause quite significant differences as the twins age. Epigenetic markers change the dynamics of brain development and can make a difference in the occurance of leukemia.

There are also modifications to the DNA sequences of cells, copy number variations (CNVs) are multiple (sometimes hundreds or thousands of times over) repeats of short (2+ base pairs) DNA sequences. These also occur as the cells differentiate and divide to form tissues and organs. Twins show significant differences there too as this is not a deterministic mechanism in development.

I can't find any references to twins showing asymmetric AIS. but the number of variants requiring this makes it sounds like its possible. If you have a reference post it and I can have a look?

note added: this paper shows that methylation profiles appear identical at least in utero.


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What's the difference between releasing hormones and tropic hormones?

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I've been reading my textbook and two terms have appeared that, after a bit of looking, I still can't seem to be able to distinguish. Here's what the textbook says (McGraw Hill Bio 12, 2011):

After receiving signals from various sensors in the body, the
hypothalamus secretes what are referred to as releasing hormones,
which often travel to the pituitary gland. The releasing hormones
stimulate the pituitary gland to secrete hormones that act on other
endocrine glands. Hormones that stimulate endocrine glands to release
other hormones are called tropic hormones. (pg. 394)

From the work I've done, it all seems to indicate that releasing hormones regulate the secretion of other hormones, and that tropic hormones target and stimulate other endocrine glands (to release hormones). And yet my textbook appears to use the terms separately later on as if they're related rather than identical (e.g.: "the pituitary gland is controlled by the hypothalamus via releasing hormones and it secretes tropic hormones" (pg. 396)). So are they identical? And if not, what distinguishes between them?

I've been reading my textbook and two terms have appeared that, after a bit of looking, I still can't seem to be able to distinguish. Here's what the textbook says (McGraw Hill Bio 12, 2011):

After receiving signals from various sensors in the body, the
hypothalamus secretes what are referred to as releasing hormones,
which often travel to the pituitary gland. The releasing hormones
stimulate the pituitary gland to secrete hormones that act on other
endocrine glands. Hormones that stimulate endocrine glands to release
other hormones are called tropic hormones. (pg. 394)

From the work I've done, it all seems to indicate that releasing hormones regulate the secretion of other hormones, and that tropic hormones target and stimulate other endocrine glands (to release hormones). And yet my textbook appears to use the terms separately later on as if they're related rather than identical (e.g.: "the pituitary gland is controlled by the hypothalamus via releasing hormones and it secretes tropic hormones" (pg. 396)). So are they identical? And if not, what distinguishes between them?

I've been reading my textbook and two terms have appeared that, after a bit of looking, I still can't seem to be able to distinguish. Here's what the textbook says (McGraw Hill Bio 12, 2011):

After receiving signals from various sensors in the body, the
hypothalamus secretes what are referred to as releasing hormones,
which often travel to the pituitary gland. The releasing hormones
stimulate the pituitary gland to secrete hormones that act on other
endocrine glands. Hormones that stimulate endocrine glands to release
other hormones are called tropic hormones. (pg. 394)

From the work I've done, it all seems to indicate that releasing hormones regulate the secretion of other hormones, and that tropic hormones target and stimulate other endocrine glands (to release hormones). And yet my textbook appears to use the terms separately later on as if they're related rather than identical (e.g.: "the pituitary gland is controlled by the hypothalamus via releasing hormones and it secretes tropic hormones" (pg. 396)). So are they identical? And if not, what distinguishes between them?

I've been reading my textbook and two terms have appeared that, after a bit of looking, I still can't seem to be able to distinguish. Here's what the textbook says (McGraw Hill Bio 12, 2011):

After receiving signals from various sensors in the body, the
hypothalamus secretes what are referred to as releasing hormones,
which often travel to the pituitary gland. The releasing hormones
stimulate the pituitary gland to secrete hormones that act on other
endocrine glands. Hormones that stimulate endocrine glands to release
other hormones are called tropic hormones. (pg. 394)

From the work I've done, it all seems to indicate that releasing hormones regulate the secretion of other hormones, and that tropic hormones target and stimulate other endocrine glands (to release hormones). And yet my textbook appears to use the terms separately later on as if they're related rather than identical (e.g.: "the pituitary gland is controlled by the hypothalamus via releasing hormones and it secretes tropic hormones" (pg. 396)). So are they identical? And if not, what distinguishes between them?

1 Answer 1

The releasing hormones could also be considered tropic hormones, and indeed they fit the definition as you noticed, but aren't usually named as such.

The special thing about the ones your textbook is specifically highlighting as releasing hormones is that they communicate from the hypothalamus to the pituitary through the hypophyseal portal system, vessels that travel directly from the hypothalamus to the anterior pituitary.

Therefore, they aren't really released into the broader circulation (they can get there, but they'd be in too low a concentration). They are easily identified in a list of hormone because they all share a naming convention where they are called "____-releasing hormone" and their primary function is to cause the pituitary to release whatever is in the "_____".

In terms of overall neuroendocrine function, the "releasing" hormones all cause release of tropic hormones, which in turn cause release of hormones that affect other tissues.

Therefore, the sequence is releasing -> tropic -> non-tropic. They could have been named something else, like "primary tropic" and "secondary tropic" but this terminology keeps them separate as "tropic hormones that cause release of other tropic hormones."

E3: L4+5 = Sexual Orientation

- most of them are exclusively heterosexual
- bimodal curve: declines from "only opposite sex" and slight increase at "only same sex"
- may be attracted to other members of same sex but they interpret not acting on it as not being homosexual

• More men than women describe themselves as exclusively homosexual

- Young people who attend single-sex boarding schools are no more likely to be gay in adulthood! [however, did find that they have more homosexual experiences but that does not define orientation]

- The case of Bruce Reimer, who was raised as Brenda Reimer, and then identified as David Reimer(Ch 7): Heterosexual orientation never changed!

• Bonobos - very closely related to human
- Nearly all bonobos are bisexual
- Females have been seen to engage in homosexual act' almost every hour

• Flower beetles - 2 males
- Mount each other and deposit sperm
- If male that has been deposited on --> then copulates with a female --> so the other male may fertilize a female without even coming in contact with her (increasing his fitness unknowingly!)

- Testosterone levels during a "critical period" before the time of birth influence an animal's preference for female or male sex partners after puberty!
>> EX: Pregnant rats placed under repeated stress can give birth to male rats that show sexual preference for other male rats!

- Something similar might operate in humans

• Consequently: Higher-than-normal levels of androgens

• Result in females: More likely to show more male-typical traits

• Sexual orientation: Shifted in the homosexual direction

Testosterone status: Higher than usual in XX individuals

Prenatal testosterone status: Exposed to higher than typical amounts of prenatal testosterone

Androgen Insensitivity Syndrome (AIS)

• Mutation in gene coding for the androgen receptor, poor or not functioning
• Usually attracted to men
• Implication: Testosterone is a key biological player in the development of sexual orientation and gender in both men & women

Testosterone status: Lower than usual in XY individuals

Prenatal testosterone status: Exposed to LOWER than typical amounts of prenatal testosterone

Finger-length studies:
• How are CAH studies relevant to healthy people?
• To answer this question: Search for anatomical/functional "markers"
>> Candidate: Finger-length influenced by prenatal testosterone
>> Index finger tends to be slightly LONGER in females than males
>> 2D:4D ratio used as an index
>> 2D:4D ratio is LOWER in MALES than females

Finger-length studies
• What about gay/straight differences?

• Gay Women: Lower ratios [normal is longer 4 women]
>> Another study found a difference between "masculine" and "feminine" lesbians

• Gay Men: evidence LESS CLEAR conflicting data
>> Results from remarkably large study: Difference found ONLY between WHITE GAY and straight men (not other ethnicities)

Otoacoustic Emissions (OAEs)

• Women generate more and louder SOAEs than men

• Spontaneous (SOAEs) & click-evoked (COAEs)

• Women generate more and louder SOAEs than men louderCOAEs
>> Appears to result from exposure to androgens during prenatal life
>> Difference also exist in monkeys & sheep

Visuospatial Abilities = Mental Rotation Task
• Straight men tend to score more correct answers than straight women

• Gay men score LESS correct answers than straight men [female-shifted]
• Lesbians score more correct answers than straight women [male-shifted]

• Verbal tasks such as "List as many words as you can that begin with 'd'"
• Generally, women tend to list more words than men (W >> M)

• Gay men list more words than straight men [female-shifted]
• Lesbians list less words than straight women [male-shifted]

• Gay men recall more items than straight men [female-shifted]

Typically larger in straight men than straight women (M >> W)
* Study: Found to be SMALLER in GAY men than straight men
- No difference found between its size in gay men and women in sample
* 1 replication attempt (2001):
- Confirmed sexual dimorphism of INAH3 found size to be intermediate between the average sizes for straight men and women

• Women tend to have SHORTER sleep durations than men on average

[Female-shifts of Suprachiasmatic Nucleus found in GAY MEN]:

Observations from Family Studies:

• Concordance rate: The probability that a pair of individuals will both have a certain characteristic
-- Compare monozygotic (MZ) twins & dizygotic (DZ) twins
• MZ twins: About 52% (male) about 48% (female)
• DZ twins: About 22% (male) about 16% (female)
-- Other studies have suggested even higher rates
• Suggests a large genetic contribution: Homosexuality seems significantly heritable in both sexes

On which chromosome is the gene for male homosexuality believed to be?

X-linkage Studies:
Male homosexuality observed to be maternally loaded
- Prompted research on the X-chromosome

2nd Study (2009): Nonlinear effect
- 1st & 2nd brother have only small effects, but effect grows rapidly with 3 or more brothers

» Male fetuses produce antigens that are specific to male fetuses!
» In response, mothers produce antibodies AGAINST those antigens
» So next fetus, mom already has antibodies that will bind to antigens so ---> If antigens guide psychosexual development towards male-typical direction, antibodies will COUNTER those functions in this next fetus!
» The more male fetuses the mother has had => the stronger the immunological reaction

1. SO there is HY antigens (Minor histocompatibility antigens) coded by Y-chromosome (so only in males)

2. Every fetus (M or F) produces antigens but normally,
mechanisms in mothers exist that "TOLERATE" these antigens
3. Fraternal Birth Order Effect could result from immunological reactions to H-Y antigens
» EX: Rh disease = something analagous could cause the fraternal birth order effect

- maybe H-Y antibodies only one side of equation: every single fetus has a DIFF genotype so that's why genes also play role!

Are there records of monozygotic twins in which one experiences androgen insensitivity syndrome - Biology

Objective: Imperforate hymen is an uncommon anomaly of the reproductive tract, occurring in approximately 0.1% of newborn females. The familial occurrence of imperforate hymen in a child, her mother, and her mother’s monozygotic twin is reported.

Setting: Academic medical center.

Patient(s): Three affected family members.

Main Outcome Measure(s): Karyotype and pedigree analysis.

Result(s): The proband, presenting with peritonitis, was evaluated at age 12 for imperforate hymen because this condition was diagnosed in her mother at age 14. At age 14, the mother’s monozygotic twin was asymptomatic except for primary amenorrhea and was also demonstrated to have imperforate hymen. No other reproductive system abnormalities were known to be present in the remaining family members. Chromosomal structural analysis confirmed that the mother of the proband had no chromosomal abnormalities.

Conclusion(s): The occurrence of imperforate hymen in two consecutive generations of a family is consistent with a dominant mode of transmission, either sex-linked or autosomal. Previously reported examples of siblings with imperforate hymen suggested a recessive mode of inheritance. Taken together, these cases suggest that imperforate hymen can be caused by mutations in several genes. This case highlights the importance of evaluating all family members of affected patients. Familial examples of other developmental anomalies of the female reproductive tract also suggest a multifactorial genetic etiology.


Etymology and definitions Edit

In 1917, Richard Goldschmidt created the term "intersexuality" to refer to a variety of physical sex ambiguities. [13] However, it wasn't until Anne Fausto Sterling published an article in 1993 that the term reached popularity. [37]

According to the UN Office of the High Commissioner for Human Rights:

Intersex people are born with sex characteristics (including genitals, gonads and chromosome patterns) that do not fit typical binary notions of male or female bodies. Intersex is an umbrella term used to describe a wide range of natural bodily variations. In some cases, intersex traits are visible at birth while in others, they are not apparent until puberty. Some chromosomal intersex variations may not be physically apparent at all. [2]

According to World Health Organization: Intersex is defined as a congenital anomaly of the reproductive and sexual system.

Attitudes towards the term Edit

Some intersex organizations reference "intersex people" and "intersex variations or traits" [38] while others use more medicalized language such as "people with intersex conditions", [39] or people "with intersex conditions or DSDs (differences of sex development)" and "children born with variations of sex anatomy". [40] In May 2016, interACT published a statement recognizing "increasing general understanding and acceptance of the term 'intersex'". [41]

Australian sociological research on 272 "people born with atypical sex characteristics", published in 2016, found that 60% of respondents used the term "intersex" to self-describe their sex characteristics, including people identifying themselves as intersex, describing themselves as having an intersex variation or, in smaller numbers, having an intersex condition. Respondents also commonly used diagnostic labels and referred to their sex chromosomes, with word choices depending on audience. [10] [42]

Research on 202 respondents by the Lurie Children's Hospital, Chicago, and the AIS-DSD Support Group (now known as InterConnect Support Group) [43] published in 2017 found that 80% of Support Group respondents "strongly liked, liked or felt neutral about intersex" as a term, while caregivers were less supportive. [44] The hospital reported that "disorders of sex development" may negatively affect care. [45]

Another study by a group of children's hospitals in the United States found that 53% of 133 parent and adolescent participants recruited at five clinics did not like the term intersex. [46] Participants who were members of support groups were more likely to dislike the term. [46] A "dsd-LIFE" study in 2020 found that around 43% of 179 participants thought the term "intersex" was bad, 20% felt neutral about the term, while the rest thought the term was good. [47]

The term 'hermaphrodite' Edit

Historically, the term hermaphrodite was used in law to refer to people whose sex was in doubt. The 12th-century Decretum Gratiani states that "Whether an hermaphrodite may witness a testament, depends on which sex prevails" ("Hermafroditus an ad testamentum adhiberi possit, qualitas sexus incalescentis ostendit."). [48] [49] Similarly, the 17th-century English jurist and judge Edward Coke (Lord Coke), wrote in his Institutes of the Lawes of England on laws of succession stating, "Every heire is either a male, a female, or an hermaphrodite, that is both male and female. And an hermaphrodite (which is also called Androgynus) shall be heire, either as male or female, according to that kind of sexe which doth prevaile." [50] [51]

During the Victorian era, medical authors attempted to ascertain whether or not humans could be hermaphrodites, adopting a precise biological definition for the term, [52] and making distinctions between "male pseudohermaphrodite", "female pseudohermaphrodite" and especially "true hermaphrodite". [53] These terms, which reflected histology (microscopic appearance) of the gonads, are no longer used. [54] [55] [56] Until the mid-20th century, "hermaphrodite" was used synonymously with "intersex". [57] Medical terminology shifted in the early 21st century, not only due to concerns about language, but also a shift to understandings based on genetics. [ citation needed ]

The Intersex Society of North America has stated that hermaphrodites should not be confused with intersex people and that using "hermaphrodite" to refer to intersex individuals is considered to be stigmatizing and misleading. [58]

Disorders of sex development Edit

"Disorders of sex development" (DSD) is a contested term, [20] [21] defined to include congenital conditions in which development of chromosomal, gonadal, or anatomical sex is atypical. Members of the Lawson Wilkins Pediatric Endocrine Society and the European Society for Paediatric Endocrinology adopted this term in their "Consensus statement on management of intersex disorders". [19] [59] While it adopted the term, to open "many more doors", the now defunct Intersex Society of North America itself remarked that intersex is not a disorder. [60] Other intersex people, activists, supporters, and academics have contested the adoption of the terminology and its implied status as a "disorder", seeing this as offensive to intersex individuals who do not feel that there is something wrong with them, regard the DSD consensus paper as reinforcing the normativity of early surgical interventions, and criticize the treatment protocols associated with the new taxonomy. [61]

Sociological research in Australia on 272 "people born with atypical sex characteristics," published in 2016, found that 3% of respondents used the term "disorders of sex development" or "DSD" to define their sex characteristics, while 21% use the term when accessing medical services. In contrast, 60% used the term "intersex" in some form to self-describe their sex characteristics. [42] U.S. research by the Lurie Children's Hospital, Chicago, and the AIS-DSD Support Group (now InterConnect Support Group) published in 2017 found that "disorders of sex development" terminology may negatively affect care, give offense, and result in lower attendance at medical clinics. [45] [44]

Alternatives to categorizing intersex conditions as "disorders" have been suggested, including "variations of sex development". [22] Tony Briffa at Intersex Human Rights Australia questions a disease/disability approach, argues for deferral of intervention unless medically necessary, when fully informed consent of the individual involved is possible, and self-determination of sex/gender orientation and identity. [62] In May 2016, interACT also published a statement opposing pathologizing language to describe people born with intersex traits, recognizing "increasing general understanding and acceptance of the term 'intersex'". [41]

In May 2019, more than 50 intersex-led organizations signed a multilingual joint statement condemning the introduction of "disorders of sex development" language into the International Classification of Diseases, stating that this causes "harm" and facilitates human rights violations, calling on the World Health Organization to publish clear policy to ensure that intersex medical interventions are "fully compatible with human rights norms". [63] [64] [65] [66] [67]

Endosex Edit

Endosex is an antonym to the term intersex, first coined by Heike Bödeker in 1999. [68] According to the National Academies of Sciences, Engineering, and Medicine, "some advocates and providers are increasingly using the term". [69]

Estimates of the number of people who are intersex vary, depending on which conditions are counted as intersex. [4] The now-defunct Intersex Society of North America stated that:

If you ask experts at medical centers how often a child is born so noticeably atypical in terms of genitalia that a specialist in sex differentiation is called in, the number comes out to about 1 in 1500 to 1 in 2000 births [0.07–0.05%]. But a lot more people than that are born with subtler forms of sex anatomy variations, some of which won't show up until later in life. [70]

Anne Fausto-Sterling and her co-authors said in two articles in 2000 that 1.7 percent of human births (1 in 60) might be intersex, including variations that may not become apparent until, for example, puberty, or until attempting to conceive. [71] [72] Their publications have been widely quoted by intersex activists. [73] [74] [75]

Of the 1.7%, 1.5 percentage points (88% of those considered intersex in this figure) consist of individuals with late onset congenital adrenal hyperplasia (LOCAH). In response to Fausto-Sterling, Leonard Sax estimated that the prevalence of intersex was about 0.018% of the world's population. [4] A 2018 review reported that the number of births with ambiguous genitals is in the range of 0.02% to 0.05%. [7] Sax stated that "[f]rom a clinician's perspective, however, LOCAH is not an intersex condition." [4] He also states that Klinefelter syndrome (47,XXY), Turner syndrome (45,X), the chromosomal variants of 47,XYY and 47,XXX, and vaginal agenesis are not intersex conditions. [4] The impact of milder 'non classic' CAH varies across individuals, may be asymptomatic in some cases or a cause of infertility, and has not been extensively studied. [76]

The figure of 1.7% is still maintained by Intersex Human Rights Australia "despite its flaws", stating both that the estimate "encapsulates the entire population of people who are stigmatized – or risk stigmatization – due to innate sex characteristics," and that Sax's definitions exclude individuals who experience such stigma and who have helped to establish the intersex movement. [77]

The following summarizes prevalences of traits that have been called intersex:

Prevalences of various conditions that have been called intersex
Intersex condition Sex specificity Approximate prevalence
Late onset congenital adrenal hyperplasia (nonclassical forms) Female (males are generally asymptomatic) [78] One in 50–1000 births (0.1–0.2% up to 1–2% depending on population) [79]
Hypospadias Male One in 200–10,000 male births (0.01%–0.5%), prevalence estimates vary considerably [80]
Klinefelter syndrome Male One in 500–1,000 male births (0.1–0.2%) [81]
47, XXX genotype Female One in 1,000 female births (0.10%) [82]
Turner syndrome Female One in 2,500 female births (0.04%) [83]
Müllerian agenesis (of vagina, i.e., MRKH Syndrome) Female One in 4,500 female births (0.022%) [84]
Vaginal atresia/agenesis Female One in 5,000 female births (0.02%) [85]
Congenital adrenal hyperplasia (classical forms) None (but virilization of female infants) [79] [76] One in 10,000–20,000 births (0.01–0.02%) [76]
45,X/46,XY chromosomal mosaicism Male One in 6666 births (0.015%) [86]
XYY genotype Male One in 7000 male births (0.0142%) [87]
XXYY genotype Male One in 18,000–40,000 male births (0.0025%–0.0055%) [88]
XX genotype (male) Male One in 20,000 male births (0.005%) [89]
Ovotesticular disorder of sex development None One in 20,000 births (0.005%) [90]
46, XY Complete gonadal dysgenesis Phenotypic female [91] One in 80,000 births (0.0013%) [92]
Androgen insensitivity syndrome (complete and partial phenotypes) Genetic male [93] One in 99,000 births (0.001%) [94]
Idiopathic (no discernable medical cause) None One in 110,000 births (0.0009%) [95]
Iatrogenic (caused by medical treatment, e.g., progestin administered to pregnant mother) None No estimate
5-alpha-reductase deficiency Male No estimate
Mixed gonadal dysgenesis None No estimate
Anorchia Male No estimate
Persistent Müllerian duct syndrome Male No estimate

Prevalences of specific conditions can vary across regions. In the Dominican Republic, 5-alpha-reductase deficiency is not uncommon in the town of Las Salinas, resulting in social acceptance of the intersex trait. [96] Men with the trait are called "güevedoces" (Spanish for "eggs at twelve"). 12 out of 13 families had one or more male family members that carried the gene. The overall incidence for the town was 1 in every 90 males were carriers, with other males either non-carriers or non-affected carriers. [97]

From early history, societies have been aware of intersex people. Some of the earliest evidence is found in mythology: the Greek historian Diodorus Siculus wrote of the mythological Hermaphroditus in the first century BC, who was "born with a physical body which is a combination of that of a man and that of a woman", and reputedly possessed supernatural properties. [98] Ardhanarishvara, an androgynous composite form of male deity Shiva and female deity Parvati, originated in Kushan culture as far back as the first century AD. [99] A statue depicting Ardhanarishvara is included in India's Meenakshi Temple this statue clearly shows both male and female bodily elements. [100]

Hippocrates (c. 460 – c. 370 BC Greek physician) and Galen (129 – c. 200/216 AD Roman physician, surgeon and philosopher) both viewed sex as a spectrum between men and women, with "many shades in between, including hermaphrodites, a perfect balance of male and female". [101] Pliny the Elder (AD 23/24–79) the Roman naturalist described "those who are born of both sexes, whom we call hermaphrodites, at one time androgyni" (from the Greek andr-, "man," and gyn-, "woman"). [102] Augustine (354 – 28 August 430 AD) the influential Catholic theologian wrote in The Literal Meaning of Genesis that humans were created in two sexes, despite "as happens in some births, in the case of what we call androgynes". [101]

In medieval and early modern European societies, Roman law, post-classical canon law, and later common law, referred to a person's sex as male, female or hermaphrodite, with legal rights as male or female depending on the characteristics that appeared most dominant. [103] The 12th century Decretum Gratiani states that "Whether an hermaphrodite may witness a testament, depends on which sex prevails". [104] [105] [106] The foundation of common law, the 17th Century Institutes of the Lawes of England described how a hermaphrodite could inherit "either as male or female, according to that kind of sexe which doth prevaile." [107] [51] Legal cases have been described in canon law and elsewhere over the centuries.

Some non-European societies have sex or gender systems that recognize more than the two categories of male/man and female/woman. Some of these cultures, for instance the South-Asian Hijra communities, may include intersex people in a third gender category. [108] [109] Although–according to Morgan Holmes–early Western anthropologists categorized such cultures "primitive," Holmes has argued that analyses of these cultures have been simplistic or romanticized and fail to take account of the ways that subjects of all categories are treated. [110]

During the Victorian era, medical authors introduced the terms "true hermaphrodite" for an individual who has both ovarian and testicular tissue, "male pseudo-hermaphrodite" for a person with testicular tissue, but either female or ambiguous sexual anatomy, and "female pseudo-hermaphrodite" for a person with ovarian tissue, but either male or ambiguous sexual anatomy. Some later shifts in terminology have reflected advances in genetics, while other shifts are suggested to be due to pejorative associations. [111]

The term "intersexuality" was coined by Richard Goldschmidt in 1917. [112] The first suggestion to replace the term 'hermaphrodite' with 'intersex' was made by Cawadias in the 1940s. [57]

Since the rise of modern medical science, some intersex people with ambiguous external genitalia have had their genitalia surgically modified to resemble either female or male genitals. Surgeons pinpointed intersex babies as a "social emergency" when born. [113] An 'optimal gender policy', initially developed by John Money, stated that early intervention helped avoid gender identity confusion, but this lacks evidence. [59] Early interventions have adverse consequences for psychological and physical health. [32] Since advances in surgery have made it possible for intersex conditions to be concealed, many people are not aware of how frequently intersex conditions arise in human beings or that they occur at all. [114]

Dialogue between what were once antagonistic groups of activists and clinicians has led to only slight changes in medical policies and how intersex patients and their families are treated in some locations. [115] In 2011, Christiane Völling became the first intersex person known to have successfully sued for damages in a case brought for non-consensual surgical intervention. [34] In April 2015, Malta became the first country to outlaw non-consensual medical interventions to modify sex anatomy, including that of intersex people. [35] Many civil society organizations and human rights institutions now call for an end to unnecessary "normalizing" interventions, including in the Malta declaration. [116] [1]

Human rights institutions are placing increasing scrutiny on harmful practices and issues of discrimination against intersex people. These issues have been addressed by a rapidly increasing number of international institutions including, in 2015, the Council of Europe, the United Nations Office of the United Nations High Commissioner for Human Rights and the World Health Organization (WHO). These developments have been accompanied by International Intersex Forums and increased cooperation amongst civil society organizations. However, the implementation, codification, and enforcement of intersex human rights in national legal systems remains slow.

Physical integrity and bodily autonomy Edit

Stigmatization and discrimination from birth may include infanticide, abandonment, and the stigmatization of families. As noted in the "Intersex human rights" page, the birth of an intersex child was often viewed as a curse or a sign of a witch mother, especially in parts of Africa. [23] [24] Abandonments and infanticides have been reported in Uganda, [23] Kenya, [117] South Asia, [118] and China. [25]

Infants, children and adolescents also experience "normalising" interventions on intersex persons that are medically unnecessary and the pathologisation of variations in sex characteristics. In countries where the human rights of intersex people have been studied, medical interventions to modify the sex characteristics of intersex people have still taken place without the consent of the intersex person. [119] [120] Interventions have been described by human rights defenders as a violation of many rights, including (but not limited to) bodily integrity, non-discrimination, privacy, and experimentation. [121] These interventions have frequently been performed with the consent of the intersex person's parents, when the person is legally too young to consent. Such interventions have been criticized by the WHO, other UN bodies such as the Office of the High Commissioner for Human Rights, and an increasing number of regional and national institutions due to their adverse consequences, including trauma, impact on sexual function and sensation, and violation of rights to physical and mental integrity. [1] The UN organizations decided that infant intervention should not be allowed, in favor of waiting for the child to mature enough to be a part of the decision-making – this allows for a decision to be made with total consent. [122] In April 2015, Malta became the first country to outlaw surgical intervention without consent. [35] [36] In the same year, the Council of Europe became the first institution to state that intersex people have the right not to undergo sex affirmation interventions. [35] [36] [73] [123] [124]

Anti-discrimination and equal treatment Edit

People born with intersex bodies are seen as different. Intersex infants, children, adolescents and adults "are often stigmatized and subjected to multiple human rights violations", including discrimination in education, healthcare, employment, sport, and public services. [2] [1] [125] Several countries have so far explicitly protected intersex people from discrimination, with landmarks including South Africa, [36] [126] Australia, [127] [128] and, most comprehensively, Malta. [129] [130] [131] [132] [133]

Remedies and claims for compensation Edit

Claims for compensation and remedies for human rights abuses include the 2011 case of Christiane Völling in Germany. [34] [134] A second case was adjudicated in Chile in 2012, involving a child and his parents. [135] [136] A further successful case in Germany, taken by Michaela Raab, was reported in 2015. [137] In the United States, the Minor Child (M.C. v Aaronson) lawsuit was "a medical malpractice case related to the informed consent for a surgery performed on the Crawford's adopted child (known as M.C.) at [Medical University of South Carolina] in April 2006". [138] The case was one of the first lawsuit of its kind to challenge "legal, ethical, and medical issues regarding genital-normalizing surgery" in minors, and was eventually settled out of court by the Medical University of South Carolina for $440,000 in 2017. [139]

Information and support Edit

Access to information, medical records, peer and other counselling and support. With the rise of modern medical science in Western societies, a secrecy-based model was also adopted, in the belief that this was necessary to ensure normal physical and psychosocial development. [31] [32] [140] [141] [142] [143]

Legal recognition Edit

The Asia Pacific Forum of National Human Rights Institutions states that legal recognition is firstly "about intersex people who have been issued a male or a female birth certificate being able to enjoy the same legal rights as other men and women." [33] In some regions, obtaining any form of birth certification may be an issue. A Kenyan court case in 2014 established the right of an intersex boy, "Baby A", to a birth certificate. [144]

Like all individuals, some intersex individuals may be raised as a certain sex (male or female) but then identify with another later in life, while most do not. [145] [9] [146] [147] Recognition of third sex or gender classifications occurs in several countries, [148] [149] [150] [151] However, it is controversial when it becomes assumed or coercive, as is the case with some German infants. [152] [153] Sociological research in Australia, a country with a third 'X' sex classification, shows that 19% of people born with atypical sex characteristics selected an "X" or "other" option, while 75% of survey respondents self-described as male or female (52% as women, 23% as men), and 6% as unsure. [10] [42]

Intersex conditions can be contrasted with transgender gender identities and the attached gender dysphoria a transgender person may feel, wherein their gender identity does not match their assigned sex. [154] [155] [156] However, some people are both intersex and transgender though intersex people by definition have variable sex characteristics that do not align with either typically male or female, this may be considered separate to an individual's assigned gender, the way they are raised and perceived, and their internal gender identity. [157] A 2012 clinical review paper found that between 8.5% and 20% of people with intersex variations experienced gender dysphoria. [146] In an analysis of the use of preimplantation genetic diagnosis to eliminate intersex traits, Behrmann and Ravitsky state: "Parental choice against intersex may . conceal biases against same-sex attractedness and gender nonconformity." [158]

The relationship of intersex people and communities to LGBTQ communities is complex, [159] but intersex people are often added to the LGBT acronym, resulting in the acronym LGBTI. Emi Koyama describes how inclusion of intersex in LGBTI can fail to address intersex-specific human rights issues, including creating false impressions "that intersex people's rights are protected" by laws protecting LGBT people, and failing to acknowledge that many intersex people are not LGBT. [160] Organisation Intersex International Australia states that some intersex individuals are homosexual, and some are heterosexual, but "LGBTI activism has fought for the rights of people who fall outside of expected binary sex and gender norms." [161] [162] Julius Kaggwa of SIPD Uganda has written that, while the gay community "offers us a place of relative safety, it is also oblivious to our specific needs". [163] Mauro Cabral has written that transgender people and organizations "need to stop approaching intersex issues as if they were trans issues", including use of intersex conditions and people as a means of explaining being transgender "we can collaborate a lot with the intersex movement by making it clear how wrong that approach is". [164]

Fiction, literature and media Edit

An intersex character is the narrator in Jeffrey Eugenides' Pulitzer Prize-winning novel Middlesex.

The memoir, Born Both: An Intersex Life (Hachette Books, 2017), by intersex author and activist Hida Viloria, received strong praise from The New York Times Book Review, The Washington Post, Rolling Stone, People Magazine, and Psychology Today, was one of School Library Journal's 2017 Top Ten Adult Books for Teens, and was a 2018 Lambda Literary Award nominee.

Television works about intersex and films about intersex are scarce. The Spanish-language film XXY won the Critics' Week grand prize at the 2007 Cannes Film Festival and the ACID/CCAS Support Award. [165] Faking It is notable for providing both the first intersex main character in a television show, [166] and television's first intersex character played by an intersex actor. [167]

Civil society institutions Edit

Intersex peer support and advocacy organizations have existed since at least 1985, with the establishment of the Androgen Insensitivity Syndrome Support Group Australia in 1985. [168] The Androgen Insensitivity Syndrome Support Group (UK) was established in 1988. [169] The Intersex Society of North America (ISNA) may have been one of the first intersex civil society organizations to have been open to people regardless of diagnosis it was active from 1993 to 2008. [170]

Events Edit

Intersex Awareness Day is an internationally observed civil awareness day designed to highlight the challenges faced by intersex people, occurring annually on 26 October. It marks the first public demonstration by intersex people, which took place in Boston on 26 October 1996, outside a venue where the American Academy of Pediatrics was holding its annual conference. [171]

Intersex Day of Remembrance, also known as Intersex Solidarity Day, is an internationally observed civil awareness day designed to highlight issues faced by intersex people, occurring annually on 8 November. It marks the birthday of Herculine Barbin , a French intersex person whose memoirs were later published by Michel Foucault in Herculine Barbin: Being the Recently Discovered Memoirs of a Nineteenth-century French Hermaphrodite.

Flag Edit

The intersex flag was created in July 2013 by Morgan Carpenter of Intersex Human Rights Australia to create a flag "that is not derivative, but is yet firmly grounded in meaning". The circle is described as "unbroken and unornamented, symbolising wholeness and completeness, and our potentialities. We are still fighting for bodily autonomy and genital integrity, and this symbolises the right to be who and how we want to be." [172]

Religion Edit

In Judaism, the Talmud contains extensive discussion concerning the status of two types of intersex people in Jewish law namely, the androgynous, who exhibit both male and female external sexual organs, and the tumtum, who exhibit neither. In the 1970s and 1980s, the treatment of intersex babies started to be discussed in Orthodox Jewish medical halacha by prominent rabbinic leaders, such as Eliezer Waldenberg and Moshe Feinstein. [173]

Sport Edit

Erik Schinegger, Foekje Dillema, Maria José Martínez-Patiño and Santhi Soundarajan were subject to adverse sex verification testing resulting in ineligibility to compete in organised competitive competition. Stanisława Walasiewicz was posthumously ruled ineligible to have competed. [174]

The South African middle-distance runner Caster Semenya won gold at the World Championships in the women's 800 metres and won silver in the 2012 Summer Olympics. When Semenya won gold in the World Championships, the International Association of Athletics Federations (IAAF) requested sex verification tests. The results were not released. Semenya was ruled eligible to compete. [175]

Katrina Karkazis, Rebecca Jordan-Young, Georgiann Davis and Silvia Camporesi have claimed that IAAF policies on "hyperandrogenism" in female athletes are "significantly flawed", arguing that the policy does not protect against breaches of privacy, requires athletes to undergo unnecessary treatment in order to compete, and intensifies "gender policing", and recommended that athletes be able to compete in accordance with their legally-recognised gender. [176]

In April 2014, the BMJ reported that four elite women athletes with XY chromosomes and 5-ARD were subjected to sterilization and "partial clitoridectomies" in order to compete in sport. The authors noted that partial clitoridectomy was "not medically indicated" and "does not relate to real or perceived athletic 'advantage'." [27] Intersex advocates [ who? ] regarded this intervention as "a clearly coercive process". [177] In 2016, the United Nations Special Rapporteur on health, Dainius Pūras, criticized "current and historic" sex verification policies, describing how "a number of athletes have undergone gonadectomy (removal of reproductive organs) and partial clitoridectomy (a form of female genital mutilation) in the absence of symptoms or health issues warranting those procedures." [178]

The notion of intersex individuals can be understood in the context of sexual system biology that varies across different types of organisms. Most animal species (

95%, including humans) are gonochoric, in which individuals are of either a female or male sex. [179] Hermaphroditic species (some animals and most flowering plants [180] ) are represented by individuals that can express both sexes simultaneously or sequentially across their lifetime. [181] Intersex individuals in a number of gonochoric species, who express both female and male phenotypic characters to some degree, [182] are known to exist at very low prevalences. Although "hermaphrodite" and "intersex" have been used synonymously in humans, [183] a hermaphrodite is specifically an individual capable of producing female and male gametes. [184] While there are reports of individuals that seemed to have the potential to produce both types of gamete, [185] more comprehensive sources state that there is no known case of a human hermaphrodite since both female and male reproduction have not been observed in the same individual. [186]

In other species Edit

Intersex has been reported in gonochoric crustaceans as early as 1729. A large amount of literature exists on intersexuality for isopoda and amphipoda, with there being reports of both intersex males and intersex females. [187]

Gonadal intersex also occurs in fishes, where the individual has both ovarian and testicular tissue. Although it is a rare anomaly among gonochoric fishes, it is a transitional state in fishes that are protandric or protogynous. [188]

Intersex can also occur in non-human mammals such as pigs, with it being estimated that 0.1% to 1.4% of pigs are intersex. [189]

Research in the late 20th century led to a growing medical consensus that diverse intersex bodies are normal, but relatively rare, forms of human biology. [9] [190] [191] [192] Clinician and researcher Milton Diamond stresses the importance of care in the selection of language related to intersex people:

Foremost, we advocate use of the terms "typical", "usual", or "most frequent" where it is more common to use the term "normal." When possible avoid expressions like maldeveloped or undeveloped, errors of development, defective genitals, abnormal, or mistakes of nature. Emphasize that all of these conditions are biologically understandable while they are statistically uncommon. [193]

Medical classifications Edit

Sexual differentiation Edit

The common pathway of sexual differentiation, where a productive human female has an XX chromosome pair, and a productive male has an XY pair, is relevant to the development of intersex conditions.

During fertilization, the sperm adds either an X (female) or a Y (male) chromosome to the X in the ovum. This determines the genetic sex of the embryo. During the first weeks of development, genetic male and female fetuses are "anatomically indistinguishable", with primitive gonads beginning to develop during approximately the sixth week of gestation. The gonads, in a bipotential state, may develop into either testes (the male gonads) or ovaries (the female gonads), depending on the consequent events. [194] Through the seventh week, genetically female and genetically male fetuses appear identical.

At around eight weeks of gestation, the gonads of an XY embryo differentiate into functional testes, secreting testosterone. Ovarian differentiation, for XX embryos, does not occur until approximately week 12 of gestation. In typical female differentiation, the Müllerian duct system develops into the uterus, Fallopian tubes, and inner third of the vagina. In males, the Müllerian duct-inhibiting hormone MIH causes this duct system to regress. Next, androgens cause the development of the Wolffian duct system, which develops into the vas deferens, seminal vesicles, and ejaculatory ducts. [194] By birth, the typical fetus has been completely sexed male or female, meaning that the genetic sex (XY-male or XX-female) corresponds with the phenotypical sex that is to say, genetic sex corresponds with internal and external gonads, and external appearance of the genitals.

Signs Edit

There are a variety of symptoms that can occur. Ambiguous genitalia is the most common sign. There can be micropenis, clitoromegaly, partial labial fusion, electrolyte abnormalities, delayed or absent puberty, unexpected changes at puberty, hypospadias, labial or inguinal (groin) masses (which may turn out to be testes) in girls and undescended testes (which may turn out to be ovaries) in boys. [195]

Ambiguous genitalia Edit

Ambiguous genitalia may appear as a large clitoris or as a small penis.

Because there is variation in all of the processes of the development of the sex organs, a child can be born with a sexual anatomy that is typically female or feminine in appearance with a larger-than-average clitoris (clitoral hypertrophy) or typically male or masculine in appearance with a smaller-than-average penis that is open along the underside. The appearance may be quite ambiguous, describable as female genitals with a very large clitoris and partially fused labia, or as male genitals with a very small penis, completely open along the midline ("hypospadic"), and empty scrotum. Fertility is variable. [ citation needed ]

Measurement systems for ambiguous genitalia Edit

The orchidometer is a medical instrument to measure the volume of the testicles. It was developed by Swiss pediatric endocrinologist Andrea Prader. The Prader scale [196] and Quigley scale are visual rating systems that measure genital appearance. These measurement systems were satirized in the Phall-O-Meter, created by the (now defunct) Intersex Society of North America. [197] [198] [199]

Other signs Edit

In order to help in classification, methods other than a genitalia inspection can be performed. For instance, a karyotype display of a tissue sample may determine which of the causes of intersex is prevalent in the case. Additionally, electrolyte tests, endoscopic exam, ultrasound and hormone stimulation tests can be done. [200]

Causes Edit

Intersex can be divided into four categories which are: 46, XX intersex 46, XY intersex true gonadal intersex and complex or undetermined intersex. [195]

46, XX intersex Edit

This condition used to be called "female pseudohermaphroditism". Persons with this condition have female internal genitalia and karyotype (XX) and various degree of external genitalia virilization. [201] External genitalia is masculinized congenitally when female fetus is exposed to excess androgenic environment. [195] Hence, the chromosome of the person is of a woman, the ovaries of a woman, but external genitals that appear like a male. The labia fuse, and the clitoris enlarges to appear like a penis. The causes of this can be male hormones taken during pregnancy, congenital adrenal hyperplasia, male-hormone-producing tumors in the mother and aromatase deficiency. [195]

46, XY intersex Edit

This condition used to be called "male pseudohermaphroditism". This is defined as incomplete masculinization of the external genitalia. [202] Thus, the person has the chromosomes of a man, but the external genitals are incompletely formed, ambiguous, or clearly female. [195] [203] This condition is also called 46, XY with undervirilization. [195] 46, XY intersex has many possible causes, which can be problems with the testes and testosterone formation. [195] Also, there can be problems with using testosterone. Some people lack the enzyme needed to convert testosterone to dihydrotestosterone, which is a cause of 5-alpha-reductase deficiency. [195] Androgen insensitivity syndrome is the most common cause of 46, XY intersex. [195]

True gonadal intersex Edit

This condition used to be called "true hermaphroditism". This is defined as having asymmetrical gonads with ovarian and testicular differentiation on either sides separately or combined as ovotestis. [204] In most cases, the cause of this condition is unknown.

Complex or undetermined intersex Edit

This is the condition of having any chromosome configurations rather than 46, XX or 46, XY intersex. This condition does not result in an imbalance between internal and external genitalia. However, there may be problems with sex hormone levels, overall sexual development, and altered numbers of sex chromosomes. [195]

Conditions Edit

There are a variety of opinions on what conditions or traits are and are not intersex, dependent on the definition of intersex that is used. Current human rights based definitions stress a broad diversity of sex characteristics that differ from expectations for male or female bodies. [2] During 2015, the Council of Europe, [73] the European Union Agency for Fundamental Rights [205] and Inter-American Commission on Human Rights [206] have called for a review of medical classifications on the basis that they presently impede enjoyment of the right to health the Council of Europe expressed concern that "the gap between the expectations of human rights organisations of intersex people and the development of medical classifications has possibly widened over the past decade". [73] [205] [206]

Medical interventions Edit

Rationales Edit

Medical interventions take place to address physical health concerns and psychosocial risks. Both types of rationale are the subject of debate, particularly as the consequences of surgical (and many hormonal) interventions are lifelong and irreversible. Questions regarding physical health include accurately assessing risk levels, necessity, and timing. Psychosocial rationales are particularly susceptible to questions of necessity as they reflect social and cultural concerns.

There remains no clinical consensus about an evidence base, surgical timing, necessity, type of surgical intervention, and degree of difference warranting intervention. [207] [208] [209] Such surgeries are the subject of significant contention due to consequences that include trauma, impact on sexual function and sensation, and violation of rights to physical and mental integrity. [1] This includes community activism, [111] and multiple reports by international human rights [29] [73] [33] [210] and health [143] institutions and national ethics bodies. [32] [211]

In the cases where gonads may pose a cancer risk, as in some cases of androgen insensitivity syndrome, [212] concern has been expressed that treatment rationales and decision-making regarding cancer risk may encapsulate decisions around a desire for surgical "normalization". [31]

Types Edit

  • Feminizing and masculinizing surgeries: Surgical procedures depend on the diagnosis, and there is often a concern as to whether surgery should be performed at all. Typically, surgery is performed shortly after birth. Defenders of the practice argue that individuals must be clearly identified as male or female for them to function socially and develop "normally". Psychosocial reasons are often stated. [19] This is criticised by many human rights institutions, and authors. Unlike other aesthetic surgical procedures performed on infants, such as corrective surgery for a cleft lip, genital surgery may lead to negative consequences for sexual functioning in later life, or feelings of freakishness and unacceptability. [213]
  • Hormone treatment: There is widespread evidence of prenatal testing and hormone treatment to prevent or eliminate intersex traits, [214] associated also with the problematization of sexual orientation and gender non-conformity. [214][215]
  • Psychosocial support: All stakeholders support psychosocial support. A joint international statement by participants at the Third International Intersex Forum in 2013 sought, amongst other demands: "Recognition that medicalization and stigmatisation of intersex people result in significant trauma and mental health concerns. In view of ensuring the bodily integrity and well-being of intersex people, autonomous non-pathologising psycho-social and peer support be available to intersex people throughout their life (as self-required), as well as to parents and/or care providers." [This quote needs a citation]
  • Genetic selection and terminations: The ethics of preimplantation genetic diagnosis to select against intersex traits was the subject of 11 papers in the October 2013 issue of the American Journal of Bioethics. [216] There is widespread evidence of pregnancy terminations arising from prenatal testing, as well as prenatal hormone treatment to prevent intersex traits. Behrmann and Ravitsky find social concepts of sex, gender and sexual orientation to be "intertwined on many levels. Parental choice against intersex may thus conceal biases against same-sex attractedness and gender nonconformity." [158]
  • Medical display. Photographs of intersex children's genitalia are circulated in medical communities for documentary purposes, and individuals with intersex traits may be subjected to repeated genital examinations and display to medical teams. Problems associated with experiences of medical photography of intersex children have been discussed [217] along with their ethics, control and usage. [218][219] "The experience of being photographed has exemplified for many people with intersex conditions the powerlessness and humiliation felt during medical investigations and interventions". [218]
  • Gender dysphoria: The DSM-5 included a change from using gender identity disorder to gender dysphoria. This revised code now specifically includes intersex people who do not identify with their sex assigned at birth and experience clinically significant distress or impairment, using the language of disorders of sex development. [220]
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  346. Krob, G. Braun, A. Kuhnle, U. (January 1994). "True hermaphroditism: Geographical distribution, clinical findings, chromosomes and gonadal histology". European Journal of Pediatrics. 153 (1): 2–10. doi:10.1007/BF02000779.
  347. ^
  348. Rosenfield, Kevin A. (2018), "Hermaphrodite", in Vonk, Jennifer Shackelford, Todd (eds.), Encyclopedia of Animal Cognition and Behavior, Cham: Springer International Publishing, pp. 1–2, doi:10.1007/978-3-319-47829-6_329-1, ISBN978-3-319-47829-6 , retrieved 27 April 2021

The term "hermaphrodite" has sometimes been used to refer to humans whose biological sex is ambiguous. This usage has fallen out of favor and in any case was technically incorrect. The essential characteristic of hermaphrodites is the ability to reproduce as both male and female. No such case has been identified in any human

Any experts on Twins out there?

So both of our boys along with their wife/girlfriend told us that they were expecting in November. How exciting. They're only 13 days apart between both due dates.

Anyhow, our youngest son and his girlfriend are having TWINS. We can't wait. We don't know the gender yet but the doctor has told them that they are identical. Here's where my question is. people have been asking if they're having twin boys/twin girls or one of each. Is it even possible to have identical twins that are of different genders? I dont have the slightest clue when it comes to twins so I did some reading up on it and they say its VERY rare but identical twins CAN be two different genders.

How. I'm sure it has to do with actual DNA and genetics and whatnot, but to me, identical means identical (meaning they both have the same "nether regions", no?)

Can someone with more brain cells explain it more? Thanks LOL


Loosing Boo Boo


DIS Veteran

Mom of twins. It is a common question!

No, boy and girl twins cannot be identical (or, at least they aren’t usually). Congratulations!

ETA: I think this explains your question pretty well, and has a good diagram.

It’s “exceedingly rare” to have “semi-identical” twins that are male and female, with only two documented cases, ever.


DIS Veteran


Dis Veteran

Kitty 34

Hums in her sleep


DIS Veteran

No it’s not possible to have identical twins with different genders..

They are from one fertilized egg.


Ok all you A cattle, get in .


DIS Veteran

Boy/Girl twins here. As Pea said you’d be amazed how often it’s asked and mine don’t even look alike, lol. They’ll argue with you too.

Congrats to them! Have them practice the polite nod and moving on because every other person will stop them and want to tell you about all the twins they have every known.


WDW PreTrip and Trip Moderator

To answer your questions, there can be 4 different ways that twins are conceived. Identical can only be one gender. One egg is split into two. We were reading though, how they can have some different traits. Like Adler, is very laid back and Owen, smiles a lot, but he is the grump of the two.

My daughter had identical twins in January. They found out last July, that they could develope twin/to/twin syndrom. She had to be checked by a specialist and have an ultra sound done every 2 weeks. The boys were born in January 3 weeks early and weight 6.5 each. I saw her the day before she went into Labor and I literally did not recognize her. Anyways, I actually took Family Leave to help and I still am helping to this day. The advice is to keep them on the same feeding schedule, but, but babies can purse their little lips and turn their heads and refuse to eat. I swear Owen still wonders why he has to eat sometimes. They will be 4 months Saturday and they slept through the night for the first time last night. It truly is a luck of the draw on when babies sleep through the night.

I watch the twins on Monday, Thursdays and Friday. I swear sometimes they tag team me. As soon as I get one to sleep for a nap, the other one will wake up. There is no down time.

My advice, get a exercise bouncy ball, pacifiers are a Godsend, if they will take them. The twins mostly refuse, which makes it hard. Keep a changing table right in the living room. I swear, they will go through 3 outfits a day. We started stocking up on Costco diapers, 1 & 2's. It is amazing how many diapers 2 babies will go through.

It is funny, how many twin stories I have heard. Never knew, so many people have had a set of twins. My daughter ordered me Insomonia Cookies, which is in Oshkosh Wisconsin and the delivery guy told me, his twins are 21.

Did I mention I had 2 other grandsons, born a week before these 2 and the other 6 months. Plus I have 4 more, all born 3 years ago. I have 8 grandchildren in 3 years. My 4 kids all got married within 9 months of each other, and now they are all having babies. And yes, I do help out with the others, and work 30 hours a week. Thank goodness, I mostly do my work on my phone and lap top.

Title: Pediatric Management of Ambiguous and Traumatized Genitalia

Updates of Clinical and Educational Sexology are intended to provide state-of-the-art education for AASECT members and other professionals on matters relevant to the practice of sexuality education, counseling and therapy. At the direction of AASECT&rsquos Professional Education Committee, and with the oversight of AASECT&rsquos president, executive director and Board of Directors, these Updates will offer readers who fulfill certain designated criteria an opportunity to receive AASECT Continuing Education credits relevant to AASECT certification procedures. We anticipate publishing Updates on a bi-monthly basis as a special feature of Contemporary Sexuality.

Milton Diamond, Ph.D., has training in Anatomy, Psychology and basic medicine and identifies as a sexologist. He has been on the faculty of the University of Hawaii, John A. Burns School of Medicine, for almost 40 years. He has done much in the field of sex education and teaching but is recognized mostly for his research and publications that include more than 100 articles and 10 books.

This article is adapted from: Diamond M. (2004). Sex, gender, and identity over the years: A changing perspective. Child and Adolescent Psychiatric Clinics: Sex and Gender 13 (3): 591-607 and Diamond, M. (1999). Pediatric management of ambiguous and traumatized genitalia. The Journal of Urology 162: 1021-1028.

Please refer to the latter article for the full list of references available online at PCSS/articles/1961to1999/1999-pediatric-management.html.

Intersexed persons have a biologic/medical condition that is not uncommon. It is a diagnosis that is shared by as many as 1 percent of the population. 1 It has been estimated that in the United States, the incidence of intersex conditions with ambiguous genitalia is about 1 in 2000 overall, when including those who have typical looking genitalia the incidence approximates 1 in 100 (Fausto-Sterling, 2000). Only those conditions that are accompanied by ambiguous genitalia are detected routinely at birth.

Over the last 40 years there have been a significant number of articles and chapters written about how to manage cases of ambiguous genitalia. Almost all of them offer advice that is based on the work of John Money and, at first, John and Joan Hampson, then later with Anke Ehrhardt. These investigators, studying intersexed individuals, basically had extrapolated from their clinical research several concepts that they thought would lead to better management. While not using these exact words, the following precepts developed.

1. Individuals are psychosexually neutral at birth.

2. Since the appearance of the genitalia is considered crucial, surgery should reduce genital ambiguity. For females. any large clitoris is to be reduced or removed for males with less than an adequate penis, since it is easier to make a vulva and vagina than a functional penis, the preferred surgical approach is sex reassignment.

3. These basic rules should hold regardless of etiology of the genital ambiguity (or trauma).

4. There should be no change of gender after 2 years of age.

Over time the limits to what constituted a large clitoris came arbitrarily to be one greater than 0.9 cm and a small penis sufficient to warrant surgery was one smaller than 2.5 cm. These guidelines can still be found in contemporary texts despite their underlying rationale having been challenged starting as early as 1959 by Cappon and colleagues (Cappon, Ezrin & Lynes, 1959). They have basically held, with few modifications, until they were most strongly challenged in the 1990s (Diamond & Sigmundson, 1997 Diamond, 1999).

The principles of Money and colleagues were particularly reinforced by the publication, in the 1970s, of a string of papers reporting on a set of healthy monozygotic male twins whose genitals were unambiguous. One needed attention after his penis was accidentally burned off when an electric cautery was used for phimosis repair. It was recommended that the traumatized child be castrated, have a vulva and vagina fashioned and be reared as a girl. This treatment was seen also as an unparalleled opportunity to confirm the theory of sexual neutrality at birth which was being challenged (Diamond, 1965). This sexual neutrality theory might be considered a simplistic &ldquoblue room / pink room&rdquo construct of sex identity which holds, in essence, that if a child is raised in a &ldquoblue room&rdquo environment the child will develop into a boy and man and, if raised in a &ldquopink room&rdquo environment, the child will develop into a girl and woman.

The twins were evaluated regularly at The Johns Hopkins Hospital and, in a series of celebrated publications (Money & Ehrhardt, 1972 Money, 1973 & 1975 Money & Tucker, 1975), their psychosexual development was described to about the onset of puberty: the one surgically reassigned as a girl and the other identical twin, in effect, a control. Glowingly relating remarkable results, Money wrote in 1975: &ldquoNo one . would ever conjecture [that Joan was born a boy]. Her behavior is so normally that of an active little girl, and so clearly different by contrast from the boyish ways of her twin brother, that it offers nothing to stimulate one&rsquos conjectures (Money 1975).&rdquo Reported in professional publications and the national media. these writings dramatically confirmed the plasticity of gender: an infant, born as an unambiguous male, had been surgically reassigned as female and successfully reared as a normal girl.

Drawing on this research and theory of psychosexual development, pediatricians caring for infants with ambiguous genitalia inferred that genetic makeup and prenatal endocrinology could be ignored in the clinical assignment of sex. The reported success of the &ldquotwin case&rdquo substantiated for clinicians the earlier reasoning that the penis had to be plainly absent or present from infancy on, and that these children could be raised as girls or boys with no hint of abnormality. Accordingly pediatric surgeons would strive to benefit these patients by &ldquonormalizing&rdquo ambiguous genitalia: reducing enlarged clitorises (eliminating visible penis-like structures in babies assigned as females) and, because of the technical difficulty creating functional and cosmetically believable male genitals, refashioning anomalous male genitalia as female. This became the standard of practice to the extent that, in 1996, the American Academy of Pediatrics published:

&ldquoResearch on children with ambiguous genitalia has shown that sexual identity is a function of social learning through differential responses of multiple individuals in the environment. For example, children whose genetic sexes are not clearly reflected in external genitalia (i.e., hermaphroditism) can be raised successfully as members of either sex if the process begins before the age of 2 years. Therefore, a person&rsquos sexual body image is largely a function of socialization (American Academy of Pediatrics, 1996).&rdquo

The only references cited to bolster this supposition were those of John Money and colleagues. Some of these publications were more than 40 years old (e.g., Money, Hampson & Hampson, 1957). In essence, no long-term, large-scale follow-up had been done in all those years to substantiate the claim. Indeed, evidence had been accumulating which refutes it.

At least three major types of evidence against the postulates were apparent. These three factors were most important in challenging the standard of practice (or at least should have been). The First type of evidence was the visible appearance, also in the 1950s and 1960s, of the phenomenon and recognition of transsexualism. Here were obviously a large number of individuals with unambiguous genitalia and unambiguous rearing who were denying both. Social rearing was obviously not having the intended effect even among these seemingly anatomically normal persons. They were certainly saying that the genitals they had were not the ones they thought they should have.

The Second factor was the developing of intersex support groups in the 1990s. These were groups like those for Androgen Insensitivity Syndrome (AIS), Klinefelter&rsquos syndrome, Turner&rsquos syndrome, and patients with congenital adrenal hyperplasia (CAH). In particular, the formation of the Intersex Society of North America (ISNA), as a sort of umbrella organization that was comprised of intersexed individuals of all categories, was critical. Group membership in ISNA includes adults who were surgically &ldquonormalized&rdquo as children, generally without being told, and others with intersex conditions who have not had surgery. Having unsuccessfully attempted to dialogue with medical organizations about their treatment, some persons from these groups had taken to picketing hospitals and conferences. Unlike those with neonatally surgically corrected cleft palates, for instance, these intersex patients were condemning physicians for their surgeries and for withholding the truth about their medical condition and treatment.

A Third factor was a chorus of dissenting voices such as mine starting in the 1960s (Diamond, 1965, 1976, 1979, and 1996) and others like Zuger (1970, 1975), Dewhurst & Gordan (1963, 1969), and Armstrong (1964), and others reporting on cases of sex reassignment that didn&rsquot work (Burns, Segaloff & Carrera, 1960 Dicks & Childers, 1934 Ghabrial & Girgis, 1962 Khupisco, 1995). These cases were typically individual reports in the literature that told of XY individuals who were somehow reared as girls, usually due to some hypospadic condition leading to a mis-assignment as females or to being assigned as females due to micropenis or traumatic loss of the penis. Despite such rearing these individuals then found their &ldquotrue feelings&rdquo were those of males, which forced them to switch their gender. Most often these switches occurred at puberty. That is the time it would be most anticipated to occur since it is then that the neural behavioral biases organized by prenatal genetic-endocrine (androgenic) influences are most strongly activated.

Probably the most notable report of such a case is that of John/Joan, the twin who was reported to have been a successful sex reassignment. Early indications that Joan was not doing well as a female (Diamond, 1982) preceded a long-term follow-up (Diamond & Sigmundson, 1997a), that eventually led to changed recommendations for surgery. Instead of supporting the original claims that a typical boy could have his gender successfully reassigned to that of a girl, the new report documented the opposite. At the age of 14 years, despite being reared as a girl and undergoing psychiatric counseling and an estrogen regimen to reinforce a female identity, Joan reassigned himself to live as a boy. He never had accepted his original gender reassignment. Other cases where the sex reassignment of intersexed children was rejected also were reported (Ghabrial & Girgis, 1962 Reimer, 1996). These new findings (Diamond & Sigmundson, 1997a), with their implications for general and typical gender development, were reported immediately on the front page of the New York Times and in the pages of other major popular and medical media. 2

The new findings in this case indicated that people were psychosexually biased and predisposed at birth. The belief that one&rsquos sexual identity could be modified easily by rearing and that individuals were psychosexually neutral at birth lost its footing and a dramatic shift in thinking about the management of intersex conditions gained momentum. New principles for the management of intersexuality were provided (Diamond & Sigmundson, 1997a).

The most basic recommendation was that the intersexed infants should be assigned a gender that is not based on the appearance of the genitalia and chance of good cosmetic surgery, but on a specific diagnosis of the exact condition and the best prediction of the child&rsquos future choice of identity. It was also recommended that any cosmetic, nonmedically essential surgery be postponed. and that intersexed children and adolescents should be allowed to make their own decisions as to how they want to live and be treated. Other recommendations were that male infants who had a micropenis should be reared as boys, unless evidence for managing them otherwise was presented. This had been successful in the past (Reilly & Woodhouse, 1989) and subsequently was also found to be successful (Wisniewski et al., 2001). The secrecy that most often was recommended to accompany genital surgery and sex reassignment was rejected. Honesty and information was to be provided and it was also recommended that, whenever possible, intersexed persons were to be put into contact with others who have the same condition. It also was recommended that the child and parents be given ongoing counseling.

Other Types of Ambiguous Genitalia

Findings from large groups of individuals with ambiguous genitalia caused by reductase deficiency are particularly revealing. Intersexed individuals with 5-alpha reductase deficiency have been studied in the Dominican Republic, Brazil and elsewhere while individuals with 17-beta dehydrogenase deficiency have been researched in Israel and Gaza as well as elsewhere. These individuals, although reared as girls due to their female appearing genitalia at birth, almost always switched to living as males if the culture allowed (e.g., see Imperato-McGinley, Peterson et al. 1979a Imperato-McGinley, Peterson et al, 1979b).

I have worked in Israel and Gaza with Ariel Rösler, Ronny Shtarkshall, Rhagda El-Shawa and others. This intersex condition is common particularly among certain Arab groups there is a great deal of intermarriage among cousins and this is a known genetic trait that frequently reappears. Male individuals with this condition are born with female-looking external genitalia and are raised accordingly. Some 50% of the babies born in Gaza are born at home and the births are attended by a midwife. Close examination of the genitalia is not usual even in communities where intersexuality is not uncommon. This society, as most Islamic ones, is quite sex segregated, and nudity is rare and discouraged. Discussion of any sexual matters, even medical conditions, is considered inappropriate. Modesty is a goal.

Children with a 17-beta dehydrogenase deficiency can look completely female as infants. They masculinize as they mature to puberty. Intersexed individuals living in Gaza, Palestinian National Authority, of different ages, were interviewed. Among these were persons that switched to living as males as well as several adults still living as females. Also interviewed were parents. siblings, professionals of different specialties, and others in Gaza familiar and unfamiliar with this condition.

Intersexed persons who were interviewed claimed to be aware of not being girls/female from early age. This was often verbally expressed even before genital masculinization was recognized. Demonstrated male behaviors by an intersexed child were often the reason for the parents to first become aware of the condition. Those older individuals who remained living as women did so due to cultural conditions that prevented their switching. They were aware they were male but considered themselves socially restrained from switching to live as men and believed they were thus also fulfilling the will of Allah.

Admittedly, there are advantages to living as male in a culture such as that of Gaza. The switch from female to male living, however, seems more due to behavioral and psychological affinities and identity with males as males rather than due to rejection of females or the female condition. Following the switch such individuals seek surgical assistance in reconstruction of their genitalia to remove the chordae, closure of any perineal cleft, and refashioning of the genitalia to look more masculine.

Another condition is deserving of mention: cloacal exstrophy. This is a non-intersex condition in which genetic males have a pelvic field defect resulting in the absence of typical genitalia. Although usually castrated and assigned and raised as girls from birth these children generally declare themselves to be boys and elect to switch from their gender of rearing to live as males. Reiner (2004) has written, &ldquoMales who were born with cloacal exstrophy, whether raised as male or castrated at birth and raised as female, demonstrate psychosocially and psychosexually dominant male-typical tendencies. It seems that prenatal androgen exposure (and perhaps sex chromosome-specific neuronal properties) influences gender role, and at least sometimes, creates male sexual identity.

Shift in Stigma: Atypical Versus Disorder

Intersex conditions are no longer seen universally as disorders or errors of development but are increasingly being seen as &ldquovariations&rdquo of life. This change occurred rapidly among those who are themselves intersexed, but is ongoing among the medical community. It has been advocated that intersexuality be considered and labeled with a more neutral term and seen as a condition without stigma rather than as a disorder (Diamond & Sigmundson 1997b). Humiliation and shame need not accompany and taint the medical or social circumstances - especially where such humiliation and shame result in the need for psychiatric care. Seeing intersexuality as a common variation - rather than as a stigmatizing condition - is an ongoing process, but one that should prove easy for clinicians to eventually adopt and foster. (See also Diamond & Watson, 2004.)

Change in Medical Practices: Standards

Standards of care for intersex conditions have changed markedly. In 2000, the American Academy of Pediatrics modified their standards in recognition of the new evidence (American Academy of Pediatrics, 2000). Similarly, in 2001 the British Association of Pediatric Surgeons modified their standard of care for intersexed children (Rangecroft et al., 2001).

Legal Considerations: Recent Developments

In 1998, the Constitutional Court of Colombia, South America, ruled that sex reassignment of individuals would no longer be legal in that country. The Court&rsquos purported goal was, &ldquoforcing parents to put the child&rsquos best interest ahead of their own fears and concerns about sexual ambiguity&rdquo(Greenberg & Chase, 2003). The Columbian Constitution guarantees free development of one&rsquos own personality, which implies a right to define one&rsquos own sexual identity.

Early in 2000, a North American Task Force on Intersex was formed. With a broad interdisciplinary board as consultants, their goal is to gather follow-up data from clinics and physicians about their treatments and results regarding intersex management. In 2002, a meeting was held in Phoenix, Arizona, with the specific hope that sufficient new data might be reported. Some new findings were gathered and presented. It was acknowledged, however, that anecdotal reports were still the norm.

Where Are We Now?

Many physicians who formerly reassigned the sex of males who had traumatic early loss of the penis or were born with a micropenis are now more likely to believe that if there were no accompanying intersex condition, such procedures would be a thing of the past. The evidence indicates that past infant cosmetic surgery may not succeed. Procedures exist that can provide a phallus for the affected boy should he desire one. Surgeons also are less likely to reduce an enlarged clitoris in a girl who has CAH. Many others are critically examining how the new and old research regarding intersex treatment should be evaluated. Increasingly, consultation from medical ethicists is being sought. This is a marked step forward.

Two other gender-related matters pertain to psychological management and deserve discussion. One involves dealing with homosexuality. In individuals who are diagnosed as having an intersexed condition, considerations of sexual orientation exist at a different level. This factor deserves discussion with the adolescent. A parallel issue in management is how intersexed individuals are treated when, and if, they present for gender reassignment. These patients often complain that they are not given credit for their own feelings. When they seek reassignment, the attitude with which they are met and the treatment they receive is often similar to that of transsexuals they feel as if they are made to prove themselves.

Clinical Advice and Summary

The area of intersex syndromes is one of intense activity and transformation. Change is rapid among the intersex populations themselves. Many have come out of their closets in a way that was unheard of only a few years ago and they operate with a new degree of activism. Instead of seeing themselves as men or women, some are identifying openly as intersexed or are willing to mix and match gender and sex.

Clinicians should be open to what their young patients tell them and help them probe their questions and doubts about identities and preferred behaviors. The medical communities are changing markedly. Physicians should be aware of the shifting attitudes and needs of their patients and be aware that one&rsquos sexual profile is complex and is not made up only of what gender-typical or -atypical behaviors are manifest, or what type of sexual orientation is professed. One&rsquos sexual profile is a constellation of a host of factors that should be explored to get a full appreciation of the patient&rsquos feelings and understandings. 3 This is not intrusive and usually will be welcomed by those patients who want their therapist to be able to truly understand them. Lastly, it should be kept in mind that all patients, regardless of age, need to be dealt with as individuals, not as a &ldquocondition.&rdquo


1 Much depends upon how intersex is defined. The narrow definition holds that intersex is a condition that is marked by genital ambiguity. Obvious cases are those with congenital adrenal hyperplasia (CAH) or partial androgen insensitivity syndrome (PAIS). A broad definition includes any individual whose biology includes an identifiable mixture of male and female characteristics, regardless of the appearance of the genitalia at birth. Examples here are persons who have the complete androgen insensitivity syndrome or Klinefelter&rsquos syndrome.

2 The case justified such coverage because the reported success of John&rsquos reassignment to Joan had become one of the most frequently cited clinical cases, not only in medicine but also in psychology, women&rsquos studies, political science, and other disciplines.

3 The mnemonic PRIMO is convenient for recalling those five areas that most need probing to get a broad and accurate profile of any individual: gender Patterns. Reproduction, sexual and gender Identity, sexual Mechanisms, and sexual Orientation.


Several national and international organizations now exist to provide support and information to individuals with interests in intersexuality [Details correct as at 2004]:

Intersex Society of North America (ISNA)
979 Golf Course Drive, #282, Pohnert Park, CA 94928

The ISNA is a leading advocate for reform of the present standards of treatment of intersexed individuals. The organization produces excellent resources useful to both educators and therapists.

Androgen Insensitivity Syndrome Support Groups (AISSG)

P.O. Box 429, Oldham, Lancs, OL4 4ZT, United Kingdom

P.O. Box 2148, Duncan, OK 73534-2148, USA
[email protected]

P.O. Box 1089, Victoria 3028, Australia

This organization offers support and information to individuals and parents concerning androgen insensitivity syndrome as well as a variety of other conditions related to ambiguous genitalia. The organization&rsquos Web site contains a wealth of useful information and is extensively linked to resources throughout Europe and North America.

North American Task Force on Intersex (NATFI)

A multidisciplinary task force organized to examine the current treatment of intersexuals.

Intersex Support Group International

A support group concerned with faith-based acceptance of intersexuality.

The UK Intersex Association (UKIA)
An organization in the UK providing support and information for all intersex conditions


Diamond, M. & Yates, A. (Eds.) (2004) Child and adolescent clinics of North America: Sex and gender Philadelphia: Elsevier

Dreger, A. (1998) Hermaphrodites and the medical invention of sex. Cambridge, MA: Harvard University Press.

Dreger, A. (1999). Intersex in the age of ethics. University Publishing Group.

Colapinto, J. (2000). As nature made him. New York, NY: Harper Collins.

Eugenidis, J. (2002). Middlesex. New York: Picadon.

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

Kessler, S. (1998). Lessons from the intersexed. New Brunswick, NJ: Rutgers University Press.

Preves, S. E. (2003). Intersex and identity: The contested self. New Brunswick, NJ: Rugers University Press.


Boy or Girl? When Doctors Choose a Child&rsquos Sex
The Third Sex
Films for the Humanities & Sciences
P.O. Box 2053, Princeton, NJ 08543-2053

Hermaphrodites Speak
Redefining Sex

Is it a Boy a Girl?
The Discover Channel

Sex Unknown
NOVA 2001 (PBS)
WGBH-TV (Boston)

The Child with an Intersex Condition: Total Patient Care
ISNA $50


American Academy of Pediatrics (1996). Timing of elective surgery on the genitalia of male children with particular reference to the risks, benefits, and psychological effects of surgery and anesthesia. Pediatric, 97, 590.

American Academy of Pediatrics (2000). Evaluation of the newborn with developmental anomalies of the external genitalia. Pediatrics, 106(1), 138-42.

Armstrong, C. N. (1964). Intersexuality in man. In C. N. Armstrong & A. J. Marshall (Eds.), Intersexuality in Vertebrates including Man (pp. 349-393). London: Academic Press.

Burns, E., Segaloff, A., & Carrera, G. M. (1960). Reassignment of sex: Report of 3 cases. Journal of Urology, 84, 124.

Cappon, D., Ezrin, C., & Lynes, P. (1959). Psychosexual identification (psychogender) in the intersexed. Journal of the Canadian Psychiatric Association, 4, 90.

Dewhurst, C. J., & Gordan, R. R. (1963). Change of Sex. Lancet, 309, 1213.

Dewhurst, C. J., & Gordan, R. R. (1969). Case histories involving re-registration of sex: The intersexual disorder London: Ballieri, Tindall, & Cassall.

Diamond, M. (1965). A critical evaluation of the ontogeny of human sexual behavior. Quarterly Reviews in Biology, 40, 147.

Diamond, M. (1976). Human sexual development: Biological foundation for social development. In F. A. Beach (Ed.), Human Sexuality in Four Perspectives (pp. 22-61). New Jersey: The John Hopkins University Press.

Diamond. M. (1979). Sexual identity and sex roles. In V. Bullough (Ed.), The Frontiers of Sex Research (pp. 33-56). Buffalo, N.Y.: Prometheus.

Diamond, M. (1982). Sexual identity, monozygotic twins reared in discordant sex roles and a BBC follow-up. Archives of Sexual Behavior 11, 181.

Diamond, M. (1996). Prenatal predisposition and the clinical management of some pediatric conditions. Journal of Sex and Marital Therapy, 22(3), 139-147.

Diamond, M. (1999). Pediatric management of ambiguous and traumatized genitalia. The Journal of Urology, 162, 1021-1028.

Diamond, M., & Sigmundson, H. K. (1997a). Sex reassignment at birth: Long term review and clinical implications. Archives of Pediatric and Adolescent Medicine, 151, 298.

Diamond, M., & Sigmundson, H. K. (1997b). Management of intersexuality: Guidelines for dealing with persons with ambiguous genitalia. Archives of Pediatric and Adolescent Medicine, 151, 1046-50.

Diamond, M., & Watson, L. A. (2004). Androgen Insensitivity Syndrome and Klinefelter&rsquos Syndrome. In M. Diamond M. & A. Yates (Eds.), Child and adolescent psychiatric clinics of North America: Sex & gender (pp. 623-640). Philadelphia: W.B. Saunders / Elsevier Science.

Dicks, G. H.. & Childers, A. T. (1934). The social transformation of a boy who had lived his first fourteen years as a girl: A case history. American Journal of Orthopsychology, 4, 508.

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

Ghabrial, F., & Girgis, S. M. (1962). Reorientation of sex: Report of two cases. International Journal of Fertility, 7: 249.

Greenberg J. A, & Chase C. Columbia high court limits surgery on intersexed infants. Volume 2003. Available at:

Imperato-McGinley, J., R. E. Peterson, et al. (1979). Male pseudohermaphroditism secondary to 5 alpha-reductase deficiency: A model for the role of androgens in both the development of the male phenotype and the evolution of a male gender identity. Journal of Steroid Biochemistry and Molecular Biology, 11(1B), 637-45.

Imperato-McGinley, J., R. E. Peterson, et al. (1979). Male pseudohermaphroditism secondary to 17B-hydroxysteroid dehydrogenase deficiency: Gender role change with puberty. Journal of Clinical Endocrinology and Metabolism, 49, 391-395.

Khupisco, V. (1995). The tragic boy who refuses to be turned into a girl. Sunday Tunes of Johannesburg. 21, May. A-1.

Money, J., & Ehrhardt, A. A. (1972). Rearing of a sex-reassigned normal male infant after traumatic loss of the penis. Man & woman/Boy & girl. Baltimore: The John Hopkins University Press.

Money, J. (1973). Prenatal hormones and postnatal socialization in gender identity differentiation. Nebraska Symposium on Motivation, 21, 221.

Money, J. (1975). Ablatio penis: Normal male infant sex-reassignment as a girl. Archives of Sexual Behavior 4, 65.

Money, J., & Tucker, P. (1975). Sexual signatures: On being a man or woman. Boston: Little, Brown.

Rangecroft. L. et al. (2001). Statement of the British Association of Paediatric Surgeons Working Party on the Surgical Management of Children Born with Ambiguous Genitalia.

Reilly, J. M., & Woodhouse, C. R. J. (1989). Small penis and the male sexual role. Journal of Urology, 142, 569-572.

Reiner, W. G. (1996). Case study: Sex reassignment in a teenage girl. Journal of the American Academy of Child and Adolescent Psychiatry, 35(6), 799-803.

Reiner W. G. (2004). Psychosexual development in genetic males assigned female: The cloacal exstrophy experience. In M. Diamond & A. Yates A. (Eds.), Child and adolescent psychiatric clinics of North America: Sex & gender Volume 13 (pp. 657-674). Philadelphia: Elsevier.

Wisniewski, A. B., Migeon, C. J., Gearhart, J. P., Rock, J. A., Berkovitz, G.D., Plotnik, L. P. et al. (2001). Congenital micropenis: Long-term medical, surgical and psychosexual follow-up of individuals raised male or female. Hormone Research, 56: 3-11.

Zuger. B. (1970). Gender role determination: A critical review of the evidence from hermaphroditism. Psychosomatic Medicine, 32, 449.

Zuger, B. (1975). Comments on &ldquoGender role differentiation in hermaphrodites.&rdquo Archives of Sexual Behavior 4: 579.

# mosaicism involving "sex" chromosomes

First, some background: A karyotype is a picture of the chromosomes in a cell. A karyotype is used to see what kinds of chromosomes a person has. It is created by taking a blood or tissue sample from a person, and then staining the chromosomes with dye and photographing them through a microscope. The photograph is then cut up and rearranged so that the chromosomes are lined up into corresponding pairs. The result is usually reported as the number and type of a person’s chromosomes, such as 45,X (the individual has 22 pairs of matched chromosomes and one X chromosome, also known as "Turner Syndrome":/faq/conditions/turner) 46,XX (the individual has 22 pairs of matched chromosomes and two X chromosomes) 46,XY (the individual has 22 pairs of matched chromosomes, one X chromosome and one Y chromosome) 47, XXY. A person is said to have a “mosaic karyotype” when he or she has one kind of karyotype in some of his or her cells, and a different karyotype in other cells. An example is when a person is said to have a 45,X/46,XX karyotype that means he or she has 46,X in some cells, and 46,XX in other cells. Mosaicism happens because sometimes cells divide incorrectly early in the life of an embryo. For instance a woman with Mosaic Turner Syndrome may have some cells that are XO (typical Turner Syndrome karyotype) and some cells that are XX (typical female karyotype). Mosaicism also occurs in milder forms of "Klinefelter Syndrome":/faq/conditions/klinefelter called 46/47 XY/XXY mosaic. In this case, the XY cells would have 46 chromosomes (a typical number of chromosomes) and the XXY cells would have 47 chromosomes.

Title: Transsexualism as an Intersex Condition

In "Transsexualität in Theologie und Neurowissenschaften: Ergebnisse, Kontroversen, Perspektiven" (translated title: "Transsexuality in Theology and Neuroscience: Findings, Controversies and Perspectives" contains articles both in German and in English), ed. by Gerhard Schreiber, Berlin and Boston: De Gruyter 2016.

This paper attempts to demonstrate that there are significant natural in-born sex differences found between the brains of those called transsexual people and others. It does so by showing the differences are due to normal genetic, hormonal and environmental forces that lead eventually to differences in the transsexual person&rsquos brain. This development brings with it feelings of dysphoria regarding one&rsquos gender identity. It is such feelings that lead to a desire for sex/gender change. These brain differences are sufficient enough to conclude that persons with a transsexual condition are intersexed. Simultaneously it is recognized that many intersexed persons will switch from their assigned gender, yet many will not.

Transsexual people are persons now also commonly referred to as trans persons or transgender persons. Those not transgender are commonly referred to as cisgender individuals. In an attempt to explain themselves trans persons often say they are convinced that they were born &ldquoin the wrong body.&rdquo They believe they have the anatomy of one sex but identity and the emotional awareness of the opposite sex. Transsexual persons are so convinced of this feeling that they desire to forego any advantages they think associated with their birth sex and seek transition to their opposite sex. And many are willing to attain the goal of transfer even at great expense financially, emotionally and socially as evidenced by divorce, separation from friends and family, and other such losses ( The natural question arises &ndash how does this feeling come about, what causes it?

The initial factor in the development of transsexualism involves genetics. Coolidge, Theda and Young, in 2002, reported, finding a strong heritable component to the condition they called Gender Identity Disorder (GID) symptomatology (Coolidge, Theda, & Young, 2002). With this they implied that gender identity was much less a matter of choice and much more a natural matter of biology. In 2013 a large study among trans persons found one third of monozygotic (identical) male twins, and approximately one quarter of female monozygotic twins, were concordant in transitioning essentially no dizygotic (familial) twins were concordant in transitioning (Diamond, 2013). And in 2014 it was reported that concordance in transition had occurred even among a trans twin pair that were reared and lived apart (Segal & Diamond, 2014). In sum these findings support a basic biological underpinning of the trans condition.

Another feature of transsexual development needs understanding. This too points to its natural biological nature. It is known that the genitals and brain develop at different times. The genitals develop early prenatally during the first 6 &ndash 12th week and they may develop in masculine or feminine form. If the genitals develop under the influence of the androgen testosterone they are masculinized. If they are not, female genitals develop. In comparison, the brain, it is believed, develops during the latter period of pregnancy and also is subject to the influence of androgen. If there is significant androgen present at that time there will be brain masculinization, if not, there will be brain feminization. It thus is clear that the brain and genitals can develop independently and under different forces (Bao & Swaab, 2011 Savik, Garcia-Falguera, & Swaab, 2010). As Reiner has said &ldquoThe etiology of gender identity may be neither obvious nor easily conceptualized. Yet what is obvious is that the presence of androgen is critical. It is the determining factor in the development of . behavioral dimorphism in humans&mdashgenital structure, . male-typical behaviors, masculinization of the brain &hellip&ldquo (Reiner, 2002).

Thus, transsexuality could develop with the genitals indicating one sex while the brain indicates the other. In cases of ambiguous genitalia the degree of masculinization of the brain may differ from that of the genitals. A strict dichotomy between male and female may not occur the shift between the sexes/genders may be partial and the individual left with feeling somewhat both male and female. This same individual might also feel female or male under different circumstances or at different times.

It is appropriate to state some generally accepted definitions. In general male and female maintaintheir usual meanings. A male has within the nucleus of each of his cells 22 pairs of thread-like structures called chromosomes. These particular chromosomes are called autosomes in recognition of a common appearance. The male also possesses a 23rd pair of chromosomes distinguished as sex chromosomes. These consist of a relatively uniform X appearing chromosome and a much smaller Y chromosome. The typical male also has two testicles, a penis, prostate and other usual features of male reproductive anatomy. A female, in contrast, has within her cells 22 pairs of autosomes and a 23rd pair of sex chromosomes with two X chromosomes. The typical female also has a vagina, two ovaries, a clitoris, uterus, oviducts and other features of female reproductive anatomy. Intersexed persons have, in the same body, both male and female biological characteristics that are typically found only separately in each sex. Often a person&rsquos sex is determined by reference to that person&rsquos chromosomal status with XY indicating male and XX indicating female. However, intersex features with their many conditions, often confound this.

Those with transsexual characteristics are defined and classified in different ways. Basically, they are those individuals who aspire to change their sex from male to female or female to male and all want to be so accepted in the gender they select going from man to woman or woman to man. Typically, such persons are said to be dysphoric in regard to their gender a condition that used to be known as Gender Identity Disorder (GID) but is currently known as Gender Dysphoria (DSM-V, 2015). This gender dysphoria refers to the impression that trans persons have that they live with a disturbing and troubling feeling of &ldquoliving in the wrong body.&rdquo Despite being assigned male at birth because of their male genitalia they think they are female and should live socially as girls or woman. If they were assigned female at birth because of their female genitalia they think they should be male and socially live as boys or men. Inherently they believe the easiest way for them to solve their dilemma is to change their sexual characteristics. While it is obvious that, in general, males can live socially as girls or women, and females can live socially as boys or men, this is not without a heavy cost. Many think it is easier and more appropriate to have what has been called sex-reassignment surgery (SRS), which they prefer to consider genital confirmation surgery or genital reconstruction surgery. Such surgery had historically been, in many countries, a requirement for legal sex/gender change recognition. Such restrictions are increasingly being removed in many jurisdictions.

Those who did change from male-to-female were commonly designated as MtF, those who switched female-to-male were designated FtM. As a group they had historically been identified as having Harry Benjamin syndrome named after the physician that first popularized the condition (Benjamin, 1966). They were considered as Women Born Transsexual (WBT) or Men Born Transsexual (MBT). Today the terms have been simplified so that the common terms used are trans women or trans men 1 .

In 2006 a consortium of physicians met to consider the evaluation and treatment of the many intersex varieties and different associated nomenclature such as hermaphrodite and pseudohermaphrodite. They agreedto designate intersex conditions as Disorders of Sex Development (DSD) (Hughes, Houk, Ahmed, & Lee, 2006) 2 .

While there are many varieties of intersex conditions, two basic types are considered. The first type, usually recognized as ambiguous at birth, is due to the infant showing no clear distinction between male and female, boy and girl. A second type of individual has typical-looking genitals but has internal intersexed features that are not apparent. These are occult intersex conditions. A person with an occult condition might, for instance, be born with both one ovary and one testis, or a gonad with combined ovarian and testicular features.

One common genetic intersex condition where the syndrome is not recognized at birth is the so-called Klinefelter syndrome (KS). Such persons have 23 pairs of typical autosomes with an additional set of sex chromosomes consisting of two or more X chromosomes and one or more Y chromosome. It is the complement of sex chromosomes that are unusual in having a variant number of Xs or Ys, e.g., XXY, XXXYY, XXYY, etc. The most common form is known as 47XXY. This condition is not usually recognized at birth because, at that time, the genitals look acceptably male and that is the way the child is generally raised. This can lead to problems, however, because persons with KS occasionally wished they were treated as girls. And typically those with the 47XXY condition, or one of its variants, develop female type breasts at puberty and come to live as women. Another common intersex situation occurs when a person has both prominent breasts simultaneously with male XY sex chromosomes, hidden testes and a vagina. This is the complete Androgen Insensitivity Syndrome (cAIS). This condition also is usually not recognized at birth because the person looks like a typical female infant to be raised as a girl.

The most common intersex variety is called congenital adrenal hyperplasia (CAH). These individuals have XX sex chromosomes, ovaries, and a hypertrophied clitoris that looks like a small penis. This condition is a natural result of an adrenal problem that results in excess androgen production and subsequent masculinization both of the body and behavior.

Less common are conditions in which persons appear to be female at birth and are raised as girls but after puberty develop as males. These are conditions where the person, congenitally, lacks crucial testosterone modifying enzymes but produces them at puberty. And when these enzymes come available they convert testosterone to the androgen dihydrotestosterone needed to masculinize the genitals. These conditions are distinguished in name by the deficiency of the enzyme involved, either 5-alpha reductase (5-alpha) or 17-beta-hydroxysteroid dehydrogenase (17-beta).

The 5-alpha condition is known to be prevalent in the Dominican Republic and the 17-beta condition relatively common among Arab populations in the Middle East. As genetic conditions they persist in groups that intermarry.

Even less common are mosaic situations in which the same individual possesses both XX and XY cell types. Such a person might have an arm considered male because its cells are all XY while the same person&rsquos leg might be considered female because its cells are all XX.

The intersex condition might manifest by differences in several of these organs or functions simultaneously, e.g., by differences in the nature of the chromosomes, gonads, genitals, or elsewhere. Since most intersex phenomena are occult, the majority of individuals with such are often unaware of their condition. For trans persons it is the brain that is intersexed in a non-apparent way.

How has the intersexuality of the transsexual brain been revealed? Early findings of sex difference were reported in the rat brain by Gorski et al. in 1978 (Gorski, Gordon, Shrayne, & Southam, 1978 ). They termed this area with the sex difference the medial preoptic nucleus (MPON). This was followed some years later by an analogous report for the human brain that the anterior commissure and massa intermedia were found sexually different. The search for sex differences in the brain became an active topic for research.

Neuroanatomical sex differences were observed in the midsagittal area of both the anterior commissure and the massa intermedia in humans. This analysis was from postmortem tissue from 100 age-matched adult males and females. While not present in all individuals, when present the anterior commissure, was an average of 12%, larger in females than in males and the massa intermedia, was an average of 53% larger in females than in males. These sex differences were found even though the brains of males were larger than those of females. Previously, these investigators had also found differences in the shape of the splenium (more bulbous) of the corpus callosum but not in the area covered (Allen & Gorski, 1991).

This same laboratory team identified other sexually dimorphic cell groups in the preoptic area of the human hypothalamus (PO-AHA) and collectively termed them the Interstitial Nucleus of the Hypothalamus with four subregions named INAH 1, 2, 3 and 4 (Allen, Hines, Shryne, & Gorski, 1989). Of these, the volume of INAH-3 was found almost three times (2.8x) as large in men as in women, and contained more than twice as many cells. Between the ages of 10 and 93 years, the nucleus decreases greatly in volume and in cell number. It had been suggested that this region was related to sexual orientation (LeVay, 1991). It is located within an area that is essential for gonadotropin release and sexual behavior in mammals. Another cell group (INAH-2) was twice as large in the male brain, but also appeared to be related in women to circulating steroid hormone levels. Since the preoptic-anterior hypothalamic area influences gonadotropin secretion, maternal behavior, and sexual behavior in several mammalian species, these results suggest that functional sex differences in the hypothalamus are related to significant sex differences in neural structure (Allen et al., 1989).

As with the Allen et al. 1989 findings, Hofman and Swaab also researched the comparable area in the human. They reported the sexually dimorphic nucleus of the preoptic anterior region of the hypothalamus (SDN-POA) in the human was markedly sexually dimorphic in volume, number of cells contained and in its structural organization. They reported finding that the volume of a putative homologue of the area originally reported for the rat brain by Gorski et al. as sexually dimorphic, was also sexually dimorphic in the adult human hypothalamus. It was more than twice as large in men as in women and contained about twice as many cells (Hofman & Swaab, 1989). Among the most significant brain differences found were those of Zhou and colleagues (Zhou, Hofman, Gooren, & Swaab, 1995). They reported finding that in males the central division of the bed nucleus of the stria terminalis (BSTc) was significantly larger than in females.

Now consider neuroanatomical features found in the brains of transsexual peoples. In 1995 Zhou et al. were the first to report finding a female brain structure in genetically male trans persons. They hypothesized these findings supported the theory that gender identity develops as a result of a normal interaction between the developing brain and sex hormones (Zhou, M. A. Hofman, Gooren, & Swaab, 1995). The area implicated was the bed nucleus of the stria terminalis (BSTc) of the hypothalamus that is sexually dimorphic in size and number of cells contained. Kruijver et al. subsequently expanded upon this finding. They found the number of neurons in the BSTc of trans women was similar to that of the females among cisgender women. In contrast, the neuron number of a FtM transsexual was found to be in the male range (Kruijver et al., 2000). This work supports the paradigm that, for transsexual persons, sexual differentiation of the brain and genitals may go in opposite directions and points to a neurobiological basis of transsexualism and the accompanying gender dysphoria.

Subsequent studies continued to substantiate these findings. Garcia-Falgueras and Swaab in 2008, using three different staining techniques, reported finding that INAH3 volume and number of neurons in the brains of those who went male-to-female (trans women) is similar to that of control females (Garcia-Falguera & Swaab, 2008). They proposed that the sex reversal of the INAH3 in trans persons is at least partly a marker of an early atypical sexual differentiation of the brain and that the changes in INAH3 and the BSTc may belong to a complex network that may structurally and functionally be related to gender identity.

Others continued this line of research. Bao & Swaab reviewed all sorts of potential influence on the sexual behavior of the developing child and found little evidence the exhibited sex differences were due to rearing (Bao & Swaab, 2011). Others did find, however, in regard to play behaviors and personality characteristics a strong influence of prenatal androgen (Mathews, Fane, Conway, Brook, & Hines, 2009 Nordenstrom, Servin, Bohlin, Larsson, & Wedell, 2002).

Work from other groups also found significant sex differences relative to trans persons that followed the proposal that a testosterone surge masculinizes the fetal brain and the absence of such a surge results in a feminine one. Gizewski et al., using fMRI, tested the cerebral activation patterns of trans women during their viewing of erotic film clips. The responses of these trans persons were more like cisfemale than cismale controls (Gizewski et al., 2009). Simon et al., using a neural-imaging technique called voxel based morphometry (VBM) measured brain components from both trans women and trans men. This VBM is a procedure using statistical methods of analysis that allows one area to be compared with another. They found many brain areas in which the gray matter structure differed from that of controls, e.g. the cerebellum, the left angular gyrus and left inferior parietal lobe. They concluded that structural brain differences exist between the brains of trans persons and control subjects dependent upon the gender expressed by the trans persons (Simon, Kozak, & Simon, 2013). The comparison agreed more with the gender expressed contemporarily than the genitals present at birth.

Transsexual people were found to have sex differences in the corpus callosum, the largest white tract in the brain. While measures of this structure have, over the years been controversial, these current authors, using Fourier descriptors of callosal contours reported finding the value of their measures for those who had gender dysphoria more strongly reflected their mental sex of gender, than their genital sex. Yokota, Kawamura, and Kameya claim the differences large enough to use as objective measures for clinical diagnosis (Yokota, Kawamura, & Kameya, 2005).

Giuseppina Rametti et al., using diffusion tensor imaging, also studied the white matter structure in the brains of trans persons. They concluded that the white matter microstructure pattern in untreated trans men is closer to the pattern of subjects who share their gender identity (males) than those who share their biological sex (females) (Rametti, Carrillo, Gómez-Gil, & Junque C, 2011).

Thickness in the cortex of the brain of trans persons has also been found significantly different. Zubiarre-Elorza et al. showed that trans men showed a subcortical brain masculinization, while the brains of trans women showed feminization particularly in regions of the right hemisphere (Zubiarre-Elorza et al., 2013). Luders et al. in 2012 also found regions of cortical thickness that differed in the brains of transsexual persons. Their results revealed thicker cortices in the brains of trans women, both within regions of the left hemisphere (i.e., frontal and orbito-frontal cortex, central sulcus, perisylvian regions, paracentral gyrus) and right hemisphere (i.e., pre-/post-central gyrus, parietal cortex, temporal cortex, precuneus, fusiform, lingual, and orbito-frontal gyrus). These findings provide further evidence that brain anatomy is associated with gender identity, where measures in trans women appear to be shifted away from gender-congruent men (Luders et al., 2012).

One last comment here is appropriate. Very recent research has reported that kisspeptin, a peptide crucial to reproduction by stimulating GnRH, has been shown to exhibit sex-reversal in persons who transitioned from male to female. This was considered to possibly reflect, at least partially, an atypical brain sexual differentiation associated with transsexualism (Taziaux et al., 2016).

Supporting these findings are many other reports documenting human male—female sex differences that show the brains of trans persons are more in keeping with their gender than their sex. It has been found, for instance, that male-to-females show sex-atypical hypothalamus activation when smelling odorous steroids. Their sense of smell is more in keeping with their gender expression than their birth sex assigned (Berglund, Lindstrom, Dhejne-Helmy, & Savic, 2008). Tests of hearing also reveal significant differences. Tests of dichotic listening, the ability to distinguish similar but different sounds, e.g. tic and toc, when simultaneously presented to each ear, have also revealed actual brain &ldquohard-wired&rdquo differences among trans women when compared with typical males. In regard to hearing their dichotic performance is more in keeping with their female gender than with their male sex (Govier, Diamond, Wolowiec, & Slade, 2010). And Burke et al. have reported finding differences in response to click-evoked otoacoustic emissions (CEOAEs). These are sounds experienced within the inner ear after an initial stimulus click is presented. Trans girls, those males with gender dysphoria, were found to have more female-typical responses than boy-typical responses. And these differences were even found in neonates (Burke, Menks, Cohen-Ketteinis, Klink, & Bakker, 2014).

Before leaving this topic of brain differences it is pertinent to remark that a difference between the brain functioning of adults and that of young children has been noted. Reiner, for example, who has a great deal of experience with both transsexual and intersex children has commented that &ldquomy own clinical experience would have to be interpreted as implying strongly that the brain states of the children (or of the adolescents, when they become adolescents) is quite different than the brain states of the adults.&rdquo (Reiner, personal communication, 2016).

Significant dental differences have even been found that differentiate trans persons. Antoszewski et al. found the metric features of teeth from trans men have an intermediate pattern between cisgender men and women (Antoszewski, Zadzińska, & Foczpański, 2009).

While more conclusive experimental data in support of the thesis presented is desirable, two recent publications have appeared that amplify and review much of the material discussed above, a paper entitled &ldquoEvidence Supporting the Biologic Nature of Gender Identity&rdquo and Bevan&rsquos book with the title &ldquoThe Psychobiology of Transsexualism and Transgenderism&rdquo (Bevan, 2015 Saraswat, Weinand, & Safer, 2015). To this investigator there seems evidence enough to consider trans persons as individuals intersexed in their brains and scant evidence to think their gender transition is a simple and unwarranted social choice.

Components and aspects of the material presented here, within a much broader context, have previously been introduced (Kraus, 2011).

My many thanks and much appreciation is due to those colleagues who have assisted me in the writing and review of this chapter. I take responsibility for any faults within, however. All faults are my own.


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Allen, L. S., Hines, M., Shryne, J. E., & Gorski, R. A. (1989). Two sexually dimorphic cell groups in the human brain. The Journal of Neuroscience, 9(2), 497-506.

Antoszewski, B., Zadzińska, E., & Foczpański, J. (2009). The metric features of teeth in female-to-male transsexuals. Archives of Sexual Behavior, 38(3), 351-358.

Bakker, F., & Vanwesenbeeck, I. (Eds.). (2006). Seksuele gezondheid in Nederland 2006 (Sexual Health in the Netherlands 2006). Delft, The Netherlands: Eburon.

Bao, A.-M., & Swaab, D. F. (2011). Sexual differentiation of the human brain: Relation to gender identity, sexual orientation and neuropsychiatric disorders. Frontiers in Neuroendocrinology, 32 214&ndash226.

Beh, H. G., & Diamond, M. (2006). Variations of Sex Development Instead of Disorders of Sex Development. Archives of Diseases of Children (26 July 2006).

Benjamin, H. (1966). The Transsexual Phenomenon. New York: The Julian Press, Inc.

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1 Transsexual people and trans women or trans >men and other designations like these, as well as others, are those suggested and preferred by WPATH, the World Professional Association for Transgender Health. They are controversial and considered differently in various cultures. Some consider it wrong to identify people as a diagnosis or with a diagnosis. Some differ in using the expressions as adjectives or nouns. Many think it is best to identify each person as they wish simply as man or woman with the pronouns he and she. Others claim it best to identify as &ldquoone with gender dysphoria.&rdquo The terms used will probably remain in a state of flux in many cultures and for many years.

Transvestites are a distinctly different group. These are persons who enjoy cross-dressing and finding relaxation and reduced anxiety in the clothes of the opposite sex. It is not clear how many of those who cross dress aspire to change their sex with surgery or modify their lives in any other way. About 0.5% of the Dutch population claimed in a large-scale representative study by the Rutgers-Nisso Group of the Netherlands that they identify more as the other sex than the gender assigned at birth. Almost 3% of the male population of the Netherlands identify as cross-dressers (Bakker & Vanwesenbeeck, 2006).

2 When the term DSD is used, it is recognized that by consensus of many physicians, it stands for "Disorders of Sex Development." See: Consensus Statement on Management of Intersex Disorders, (Lee, Houk, Ahmed, & Hughes, 2006). However, identifying these conditions as disorders is stigmatizing. Others and I prefer to see the definition as Differences (DSD) or Varieties of Sex Development rather than Disorders. See Beh & Diamond, 2006 Tamar-Mattis & Diamond, 2007 Diamond & Beh, 2008.