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INTERSEX PEOPLE - Who Are They?
1. INTERSEX PEOPLE:
Who Are They?
Presented By
Veronica Drantz, PhD
And Intersex Spokespersons Alex & Chrixs
Prepared for
Argosy University
A2Z
March 23, 2013
2. Famous Intersex People
Carolyn Cossey XXXY (Klinefelter’s)
Julia Child XY (CAIS)
Caster Semenya (CAIS?)
3. Intersex People Are Natural
"There is a spectrum of sexual
identity and intersex people
bridge this spectrum. We have a
unique vision to offer the world
and we have existed since the
dawn of humanity."
Hida Viloria – intersex activist
XX (CAH)
4. The Myth: “The Gender Binary”
Gametes are binary (eggs or sperm)
Organisms that make the gametes are not binary!
5. 23 Pairs Human Chromosomes
XX (Female), XY (Male)
Figure 25-2 Karyotype of chromosomes from a normal male. The chromosomes have
been stained with Giemsa's stain, which produces a characteristic banding pattern.
6.
7. Genetic Sex Determination
• Typical male
has Y
chromosome
• Typical
female has
no Y
chromosome
Figure 25-1 Basis of genetic sex determination. In the two-stage meiotic division in the female, only one cell survives as the
mature ovum. In the male, the meiotic division results in the formation of four sperms, two containing the X and two the Y
chromosome. Fertilization thus produces a male zygote with 22 pairs of autosomes plus an X and a Y or a female zygote with
22 pairs of autosomes and two X chromosomes. Note that for clarity, this figure and Figures 25–6 and 25–7 differ from the
current international nomenclature for karyotypes, which lists the total number of chromosomes followed by the sex
chromosome pattern. Thus, XO is 45, X; XY is 46, XY; XXY is 47, XXY, and so on.
8. Y Chromosome Has Testis-
determining Region (Gene)
Is a sex-determining gene on the Y chromosome
in placental mammals and marsupials
(Y chromosome evolved from X chromosome)
Initiates male sex determination
Located near tip of short arm of Y chromosome
Codes for SRY protein
– SRY = Sex-determining region Y
– aka testis determining factor = TDF
– Causes gonad to differentiate into testis
SRY protein is DNA-binding regulatory protein
Acts as transcription factor
Initiates transcription of cascade of genes necessary for
testicular differentiation
9. Multiple Genes Determine
Gonad Differentiation
MALES: SRY upregulates SOX9 activating expression of steroid genesis factor 1 (SF1) and
other genes responsible for testes differentiation and INHIBITING expression of WNT4
FEMALES: WNT upregulates DAX1 (when inhibited); DAX inhibits SOX9 expression and
upregulates downstream target genes that induce ovarian differentiation
http://quizlet.com/3597081/x-and-y-chromosomes-flash-cards/
10. Genes on Sex Chromosomes Are
Expressed in Brain of Embryo
XX and XY embryonic rodent brains
develop differently before gonads
develop (so hormone influence is not a
factor)
Laura L. Carruth, Ingrid Reisert & Arthur P. Arnold. Sex chromosome genes directly affect brain sexual differentiation NATURE NEUROSCIENCE 5, 933
- 934 (2002)
Phoebe Dewing, Tao Shi, Steve Horvath, Eric Vilain Sexually dimorphic gene expression in mouse brain precedes gonadal Differentiation MOLECULAR
BRAIN RESEARCH 118 (2003) http://www.shb-info.org/sitebuildercontent/sitebuilderfiles/4_vilain_et_al.pdf
11. “Organization – Activation”
Mechanism
“Prenatal hormone theory”
– Organization before birth
– Activation at puberty
12. Sexual
Differentiation
of
Internal
Genitalia
Figure 25-4 Embryonic
differentiation of male and
female internal genitalia
(genital ducts) from
wolffian (male) and
müllerian (female)
primordia.
14. Sexual Development in Mammals
Figure 25-6 Diagrammatic summary of normal sex determination, differentiation, and
development in humans. MIS, müllerian inhibiting substance; T, testosterone; DHT,
Dihydrotestosterone
15. Androgen Hormones Are Made
in Adrenal Glands and Gonads
http://www.carolguze.com/text/442-6-sexual_differentiation.shtml 17β-HSD=17-beta hydroxysteroid dehydrogenase
17. Mechanism of Steroid
Hormone Action Brain
Figure 25-18 Schematic diagram of the actions of testosterone (solid arrows) and dihydrotestosterone (dashed arrows).
18. T versus DHT effects
Sexual differentiation due to Testosterone
Seminal vesicles
Vasa deferentia
Wolffian Duct
Epidymides
Ejaculatory ducts
Sexual differentiation due to 5α reductase type 2
Urogenital sinus Prostate gland
Urogenital tubercle Penis
Labioscrotal swellings Scrotum
Urogenital folds Urethra
19. Puberty = “Activation”
Female Secondary Sex Characteristic Cause
Genitalia Enlargement of breasts, uterus, vagina Estrogen
Voice larynx retains prepubertal proportions; Lack of
high-pitched voice testicular
androgens
Hair less body hair, more scalp hair, flat- Lack of
topped pubic hair pattern testicular
androgens
Pubic and axillary hair Androgen
Mental Interest in sex Androgen
Body Narrow shoulders, broad hips, thighs Lack of
Conformation that converge, arms that diverge (wide testicular
carrying angle), female distribution of androgens
fat in breasts & buttocks
Skin Sebaceous glands more fluid (inhibit Estrogen
acne)
Alteration in typical women
20. Activation at Puberty
Tanner scales
http://upload.wikimedia.org/wikipedia/commons/thumb/0/0c/Tanner_scale-female.svg/240px-Tanner_scale-female.svg.png
http://upload.wikimedia.org/wikipedia/commons/8/8f/Tanner_scale-male.png
21. Male Is Altered Female !!!
Mammalian body plan is inherently female
Every individual’s body plan is a variation on the
female theme
– Default (female)
– Fully altered (male)
– Partly altered (intersex)
Everyone falls on some point of the continuum from
female (gynemorphic) to male (andromorphic)
This sexual body plan is organized by presence or
absence of steroid hormones during the critical
period of development
Sexual systems are activated later by steroid
hormones during puberty
22. What Is a Female? A Male?
Primary sex characteristic
– Type of gonads
Female gonad is ovary – produces eggs
Male gonad is testis – produces sperm
– Develop in fetus
– Testosterone & its derivatives are “directional”
Secondary sex characteristics
– Produced by gonadal hormones
Androgens
Estrogens
– Develop during puberty
– Hormones are “activational”
23. Sexual Identity & Orientation –
Nature or Nurture?
The genitalia are obviously organized before birth,
and we obviously do not learn or choose our genetic
sex, gonadal sex, hormonal sex, or somatic sex
But what about sexual behavior? Sexual identity?
Sexual orientation? Innate or learned/chosen?
Is the brain, like the body, organized by the
presence or absence of sex hormones before birth?
Evidence for Organization-Activation Mechanism
– David Reimer story
– Intersex people (AIS, CAH, cloacal exstrophy)
– Brain work (nonhuman mammals, humans)
24. John Money
"Neutrality-at-Birth“
Theory
“Sexual behavior and orientation as Psychologist
male or female does not have an
innate, instinctive basis”
Money, J. Hermaphroditism, gender and precocity in hyperadrenocorticism: Psychologic findings. BULLETIN OF THE JOHNS HOPKINS HOSPITAL
96:253-264 (1955)
– Postulate 1: Individuals are psychosexually neutral
at birth
– Postulate 2: Healthy psychosexual development is
intimately related to the appearance of the genitals
No evidence to support this theory (serious
flaws in Money’s statistical and research methods)
*Cappon D, Ezrin C, Lynes P. Psychosexual identification (psychogender) in the intersexed THE CANADIAN PSYCHIATRIC ASSOCIATION JOURNAL 4:90-106 (1959)
25. Milton Diamond
“Sexuality-at-Birth"
Theory
Prenatal genetic and hormonal Biologist
influences predispose at birth to a male or
female sexual identity
Inherent sexuality provides built-in "bias“ with
which the individual interacts with environment;
sexual behavior and thus gender role, are not
neutral and without initial direction at birth
Organization – Activation Mechanism
Evolutionary view
26. 1959 – Breakthrough at
University of Kansas
Phoenix CH, Goy RW, Gerall AA, Young WC.
Organizing action of prenatally administered
testosterone propionate on the tissues
mediating mating behavior in the female guinea
pig. ENDOCRINOLOGY 65:369-382 (1959)
Milton Diamond
– Felt that fellow scientists were too cautious failing to
link their animal findings to human situation
– Decided to write essay challenging psychosexual
neutrality theory
27. Diamond Versus Money
• Diamond challenges Money - 1965
• Diamond, Milton. A critical evaluation of the ontogeny
of human sexual behavior. QUARTERLY REVIEW OF
BIOLOGY 40:147 – 175 (1965)
• Over the years, animal work accumulated showing
“determining influence” of prenatal hormones
• Money responds to challenge - December 28,
1972
• Symposium of American Association for the
Advancement of Science “Sex Role Learning in
Childhood and Adolescence”
• Man & Woman, Boy & Girl: the differentiation and
dimorphism of gender identity from conception to
maturity. Baltimore, MD: John Hopkins University
Press, 1972. 311 p. (Depts Psychiatry and Pediatrics, John Hopkins Univ. Sch. Med., Baltimore, MD)
28. The David Reimer Story
“John/Joan Case”
“Nature-Nurture Experiment” involving
an identical twin
– Circumcision accident destroyed John’s penis
– Dr. Money consulted: John was “assigned” as Joan
(castration, feminizing genitoplasty, raised as girl)
John Money reported (falsely) that “Joan”
was growing up as a happy girl
John-Joan case became the foundation of standard care
– Certain intersex conditions
– Micropenis
– Accidental penile amputation in infancy
Deception of patient about their medical history is necessary
for “Optimal Gender of Rearing” process
Medical records were often falsified or destroyed
Many intersex people still do not know their medical history or
their intersex status
29. David Reimer
Story
“Joan’s turning point occurred at
the age of 14, when she, on her
own initiative, began living as a
boy, John. John recalls how
soon thereafter he finally
learned the truth, “In a tearful
episode following John’s
prodding, his father told him of
the history of what had
transpired as an infant and why.
John recalls: ‘All of a sudden
everything clicked. For the first
time things made sense and I
Colapinto, John. As Nature Made Him - The Boy Who Was
Raised As A Girl HarperCollins (2000)
understood who and what I
was.’”
Beh HG, Diamond M. An Emerging Ethical and
Medical Dilemma: Should Physicians Perform
Sex Assignment on Infants with Ambiguous
Genitalia? MICHIGAN JOURNAL OF GENDER
& LAW 7: 1-63 (2000)
30. David Reimer (1965-2004)
John Money continued to tell medical community that Joan/Brenda
was a happy girl/woman and then claims to lose track of her
Milton Diamond finds “Joan” living as David!
When David discovered his case was medically famous and that
thousands of intersex babies had suffered his plight, he cooperated
with Milton Diamond and “went public”
Milton Diamond, Ph.D. & H. Keith Sigmundson, M.D. Sex Reassignment at Birth: A Long Term Review and Clinical Implications. ARCHIVES OF
PEDIATRIC & ADOLESCENT MEDICINE 151:298-304 (1997)
Money’s view is now discredited!
31. Intersex People
Curtis Hinkle - Founder
Organization Intersex International
32. Intersexuality
Incidence: 1.7%*- 2.5% ???
Intersexual people are as natural as the rest of us
They are nature’s experiments providing
information about sexual development
Only in recent years have we been able to track
intersexual people over their lifetime and find out
about their sexual identity and orientation
They illustrate how no definition of female or male
is always “satisfying”
*Fausto-Sterling, Anne. SEXING THE BODY: GENDER POLITICS AND THE CONSTRUCTION OF SEXUALITY. Basic Books (2000)
33.
34. Sex Has Many Levels
Primary sex
characteristic
GeneticSex – Chromosomes (X & Y in mammals only)
Gonadal Sex – Ovaries/Testis
Hormonal Sex – Estrogen/Testosterone
Somatic Sex – Body anatomy/physiology
Psychological Sex - Sexual identity
and then there is
Sexual orientation
35. Translocation of SRY
Unequal gene from Y to X
Crossing-over chromosome
– XY Female
Between X and Y Swyer syndrome
During Paternal Absence or mutation of
SRY on Y produces
Meiosis females with gonadal
dysgenesis
– XX Male
XX male syndrome
SRY gene in one or
both X chromosomes,
produces infertile males
36. Variations of
Genetic Sexes
Nondisjunction of
chromosomes during
meiosis in parent’s gonad
http://www.genetic-diseases.net/down-syndrome/
– XO Female (Turner
Female)
– XXX Female
(Superfemale)
– XXY, XXXY etc. Male
(Klinefelter Male)
– XYY Male (Jacob’s
Syndrome)
– 48XYXY
37. Turner’s Syndrome
Karyotype is 44
autosomes plus XO
Ovarian agenesis or
gonadal dysgenesis
– Gonads rudimentary or
absent
– Female external genitalia
– Short stature, other
congenital abnormalities
Luria, Z., Friedman, S., and
Rose, M.D. HUMAN SEXUALITY.
New York: John Wiley & Sons
– No maturation at puberty
(1987)
38. Klinefelter Syndrome
Karyotype 47XXY
Most common sex chromosome
disorder (1 or 2 cases/1000)
Male phenotype
Hypogonadism
http://www.aurorahealt Seminiferous tubule dysgenesis
hcare.org/yourhealth/h
ealthgate/images/si555
51770.jpg – Reduced or absent spermatogenesis
– Variability in presentation is related
mainly to the timing and amount of
androgen deficiency
– Increased FSH levels (indicates low inhibin B from Sertoli cells)
– The more supernumerary sex chromosomes that exist, the more likely are detrimental physical and
mental findings
– Cryptorchidism 3X more frequent
– Taller, greater leg growth (5 and 8 years)
– Tendency for central obesity
– Minority born with small penises; testosterone cream caused penis growth; however, normal size
penis in only 77% by end of puberty; in contrast, testes normal size at birth but fail to grow normally
– Gynecomastia 30% to 90% of cases
– May have diminished body and facial hair, female pubic hair pattern, small phallus, poor muscular
development, and progressive disproportion in leg and body length, feminine fat distribution
– Fertility becomes increasingly doubtful as age advances; however, before infertility is predicted,
sperm analysis is required because paternity has been documented
Forbes, C.D. and Jackson, W.F. A COLOUR ATLAS AND TEXT OF CLINICAL MEDICINE. England: Mosby-Wolfe
(1993)
39. Klinefelter Syndrome
& Gender Expression
Infrequently discussed in medical descriptions of KS are
individuals’ concerns with gender expressions and feelings
An unknown percentage of persons who have KS experience
androgynous or feminine feelings that can develop at an
early age
Some people who have KS consider themselves to be
transgendered, others intersexed, and others transsexual; in
one study, investigators concluded that all of their KS
patients viewed their personalities as dual male and female
– A host of investigators similarly reported cases of men who had KS
who transitioned to live as women or who harbored aspects of gender
dysphoria
– Carolyn Cossey, a “James Bond girl,” was raised as boy, but changed
to live as a girl at young age, and became a famous model; her
karyotype was found to be XXXY
Shirley Ratcliffe Arch Dis Child 1999;80:192–195
40. Sex Chromosome Mosaics
A genetic mosaic is a
creature whose body is built
of a mixture of cells of two or
more different genotypes
– Fusion of different embryos to
form chimera
– Nondisjunction or mutation in
stem cell undergoing mitosis in
early embryo creating two
genetic kinds of cells
Mosaic intersex types
– 46XY/47XXY
– 46X/46XY
41. Brain
Androgen
Insensitivity
Syndrome
Caused by mutations in the gene for the androgen receptor
Recessive X-linked single gene syndrome (mother is carrier)
Genetic males - 46 XY
Testes (abdominal or inguinal) secrete testosterone
No uterus or other internal female genitalia (MIS worked)
Male internal genitalia undeveloped (Testosterone did not
work)
Female secondary sex characteristics develop (eg, breasts)
– At puberty testosterone from testes is turned into estrogen by enzyme (aromatase)
in peripheral tissues
– Often discover their condition when they fail to menstruate (No uterus)
(Julia Child – CAIS)
42.
43. Forbes, C.D. and Jackson, W.F. A COLOUR ATLAS AND TEXT OF CLINICAL MEDICINE. England: Mosby-Wolfe (1993)
CAIS People Feel Like Women!
Luria, Z., Friedman, S., and Rose, M.D. HUMAN SEXUALITY. New York: John Wiley & Sons, 1987.
44. Partial AIS (2-5): Grade 1:
normal masculinization in utero
Cannot Predict Grade 2:
male phenotype with mild defect
in masculinization (eg, isolated
Sexual Identity
hypospadias)
Grade 3:
male phenotype with severe
defect in masculinization—small
penis, perineoscrotal
hypospadias, bifid scrotum or
cryptorchidism
Grade 4:
severe genital ambiguity—
clitoral-like phallus, labioscrotal
folds, single perineal orifice
Grade 5: female phenotype with
posterior labial fusion and
clitoromegaly
Grade 6/7
Numbered I through 7 in order of increasing severity female phenotype (grade 6 if
(more defective masculinization) pubic hair present in adulthood,
Adapted from Quigley CA, DeBellis A, Marschke KB, El-Awady MK, Wilson EM, French FS. Androgen
Receptor Defects: Historical, Clinical, And Molecular Perspectives. ENDOCRINE REV, 1
6:282; (1995) with permission.
grade 7 if no pubic hair in
In: Diamond, Milton and Watson, Linda Ann. Androgen Insensitivity Syndrome And Klinefelter’s adulthood)
Syndrome: Sex And Gender Considerations. CHILD ADOLESC PSYCHIATRIC CLIN N AM 13: 623
—640 (2004)
45. Complete AIS & Gender Identity
39 subjects:
• 100% lived as women and believed that it was the best decision for them; however, this was not a
simple solution for all
• “Acceptance of assignment does not mean that assignment has been correct. It just means that
most are able to adapt and live with the handicap; however, they might have preferred other
options”
published statements from ALIAS, Agree Disagree
an AIS newsletter.
“I don’t think I am any different in 82%* 18%
feeling than if I were born XX, feel
very female.”
“All my efforts over the years in 10% 90%
presenting a female persona have
left me completely exhausted. I
might just as well have had a
mastectomy, cut my hair short and
lived as a celibate man. It would
actually have been easier I think.”
I have to “work at being a woman” 56% (dressing in a feminine way 44%
or using cosmetics or hair styles in
a way to signal “female”
unambiguously, altering selection
of clothes;
30% did above much of the time)
Considered suicide 62% 38%
Attempted suicide 23% 77%
*Indicates to me that androgen receptor is required for “alteration” of human gender identity brain region(s).
Diamond, Milton and Watson, Linda Ann. “Androgen insensitivity syndrome and Klinefelter’s syndrome: sex and gender considerations”
Child Adolesc Psychiatric Clin N Am 13 (2004) 623—640
46. Partial AIS & Gender Identity
18 subjects:
•Often ambivalent about assigned gender
•67% believed that the gender in which they were raised was best for them, whereas the
others voiced reservations
• “Gender switch” occurred at mean age of 33, range 18-46)
PARTIAL AIS
8 raised as boys 4 live as women
10 raised as girls 2 live as men*
Considered suicide 61%
Attempted suicide 17%
*Now angry about castration, vaginal reconstructions surgery, and somatic feminization by estrogen treatment since
puberty
**Attempted before switching
Diamond, Milton and Watson, Linda Ann. “Androgen insensitivity syndrome and Klinefelter’s syndrome: sex
and gender considerations” Child Adolesc Psychiatric Clin N Am 13 (2004) 623—640
48. Five Degrees of Virilization Affecting
the Urogenital Sinus and
External Genitalia in Females
Hines M, Brook C., Conway, G.S. Androgen And Psychosexual Development Core Gender Identity, Sexual Orientation And
Recalled Childhood Gender Role Behavior In Women And Men With Congenital Adrenal Hyperplasia (CAH). J SEX RES, 41: 75-81
(2004)
49. Congenital Adrenal Hyperplasia
(CAH)
Luria, Z., Friedman, S., and Rose, M.D. HUMAN SEXUALITY. New York: John Wiley & Forbes, C.D. and Jackson, W.F. A COLOUR ATLAS AND TEXT OF CLINICAL
Sons (1987) MEDICINE. England: Mosby-Wolfe (1993)
50. Frequency of CAH
Figure 4. Frequency of nonclassical and classical 21-hydroxylase deficiency in comparison with other
autosomal recessive disease incidences
Hines M, Brook C., Conway, G.S. Androgen And Psychosexual Development Core Gender Identity, Sexual Orientation And Recalled
Childhood Gender Role Behavior In Women And Men With Congenital Adrenal Hyperplasiz (CAH). J SEX RES, 41: 75-81 (2004)
51. CAH (Adrenogenital Syndrome)
Luria, Z., Friedman, S., and Rose, M.D. HUMAN
SEXUALITY. New York: John Wiley & Sons (1987)
52. Sexuality of CAH Women
More male-typical play behavior as children*
Less satisfaction with the female sex of assignment and less
heterosexual interest*
CAH girls who show the greatest alterations in childhood play
behavior may be the most likely to develop a bisexual or
homosexual orientation as adults and to be dissatisfied with
the female sex of assignment*
“The finding of greater same-sex fantasy … is consistent with
the prenatal hormonal hypothesis”**
“…excess prenatal androgens predispose some women to the
development of same-gender sexual orientation”***
“Dose-response relationship of androgens with sexual
orientation” - a study of women with various forms of CAH****
*Hines M, Brook C., Conway, G.S. Androgen And Psychosexual Development Core Gender Identity, Sexual Orientation And Recalled Childhood Gender Role Behavior In Women And Men With
Congenital Adrenal Hyperplasia (CAH). J SEX RES, 41: 75-81 (2004)
**Veniegas, Rosemary C. Biological Research on Women's Sexual Orientations: Evaluating the Scientific Evidence. J SOCIAL ISSUES, (2000)
***Pattatucci, A. M. L., & Hamer, D. H. Development And Familiality Of Sexual Orientation In Females. BEHAVIOR GENETICS, 25: 407-420 (1995)
****Meyer-Bahlburg HF, Dolezal C, Baker SE, New MI. “Sexual Orientation in Women with Classical or Non-Classical Congenital Adrenal Hyperplasia as a Function of
Degree of Prenatal Androgen Excess” ARCHIVES OF SEXUAL BEHAVIOR 1: 85-99 (2008),
53. Hypospadias
These common
conditions are
often not regarded
as intersex
condition.
But they are!
54. Figure 4.
Metabolism of Testosterone to 5_-Dihydrotestosterone
by the enzyme 5alpha-Reductase type 2 (SDR5A2).
Figure 11. Mutations in the
human 5_-reductase type 2
5_
gene (SDR5A2) reported in
patients with the syndrome
of 5_-reductase deficiency.
5_
The 5_-reductase type 2
5_
enzyme is encoded by 5
different exons and
mutations have been
reported in all 5 exons, as
well as a complete gene
deletion, small deletions of
nucleotides and splice site
mutations.
Brinkmann A. O., Androgen Physiology: Receptor and MetabolicDisorders. Nov 2009.
http://www.endotext.org/male/male3/maleframe3.htm
55. Cloacal Exstrophy
Rare, complex defect
of the entire pelvis
and its contents
Associated with
severe phallic
inadequacy or phallic
absence in genetic
males
For about 25 years,
Bladder Extrophy and absence
of the penis neonatal assignment
green arrows: everted bladder; to female sex has
blue arrows: the scrotum; been advocated for
yellow arrows: umbilcal cord affected males
56. Prenatal Androgen - Major Factor
in Development of Sexual Identity
Genetically and
hormonally
male-born
children may
identify as
males despite
being raised as
females and
undergoing
feminizing
genitoplasty at
birth
Kayla’s story
Reiner, William G. and Gearhart, John P. Discordant
Sexual Identity in Some Genetic Males with
Cloacal Exstrophy Assigned to Female Sex at
Birth. THE NEW ENGLAND JOURNAL OF
MEDICINE, 350:333-341 (2004)
57. The Sexual
Brain
Amygdala
– Part of Limbic System
– Genesis of emotions
& emotional
expression
Hypothalamus
– Homeostasis
– Neuroendocrine Control
– Instinctive Drives &
Behavior
Hunger
Thirst
Sleep
Body Rhythms
Sex
Netter, Frank H. The CIBA COLLECTION OF MEDICAL
ILLUSTRATIONS. Vol I. Nervous System. Part I. Anatomy &
Physiology. New York: CIBA (1983)
58. Sexual Behavior and Gonadal
Function Controlled by Different
Regions of Hypothalamus in
Mammals
Figure 25-28 Loci where implantations of estrogen in the hypothalamus
affect ovarian weight and sexual behavior in rats, projected on a
sagittal section of the hypothalamus. The implants that stimulate
sex behavior are located in the suprachiasmatic area above the
optic chiasm (blue area), whereas ovarian atrophy is produced by
implants in the arcuate nucleus and surrounding ventral
hypothalamus (red). MB, mamillary body
59. Biology of Sexual Identity
Fa'afafine
A broadly accepted social class in Samoa
60. Bed Nucleus of the Stria Terminalis
Figure 2: Representative sections of the BSTc innervated by vasoactive intestinal polypeptide (VIP). A:
heterosexual man; B: heterosexual woman; C: homosexual man; D: male-to-female transsexual. Bar=0.5
mm. LV: lateral ventricle. Note there are two parts of the BST in A and B: small sized medial subdivision
(BSTm), and large oval-sized central subdivision (BSTc)
Zhou, J.N. Hofman, M.A. Gooren, L.J. and Swaab, D.F.. A Sex Difference in the Human Brain and its
Relation to Transsexuality. NATURE, 378: 68-70 (1995)
BSTc is sexually dimorphic and necessary for sexual behavior in animals
Note the sex difference regardless of sexual orientation
MtF Transsexual has same BSTc volume as typical female
Size of BSTc is not influenced by sex hormones in adulthood
End point: VIP-secreting presynaptic nerve endings carrying “emotional
info” from amygdala to this nucleus of anterior hypothalamus
61. 2nd Study on BSTc
The male-to-female transsexual has a
BSTc in the female range
– S7: male, lifelong female identity, never “treated”-
within female range
FMT: number of neurons is fully within the
male range
End point: somatostatin-secreting postsynaptic
neurons in nucleus receiving VIP input from amygdala
(a) a reference man
(b) reference woman
(c) homosexual man
(d) male-to-female transsexual
Kruijver, Frank P. M., Zhou, Jiang-Ning, Pool, Chris W. Hofman, Michel A.,. Gooren, Louis
J. G And Swaab, Dick F. Male-To-Female Transsexuals Have Female Neuron
Numbers In A Limbic Nucleus. J CLIN ENDOCRINOL METAB, 85: 2034-2041 (2000)
62. Genetics of Transsexuality
MtF transsexualism
– Significant link with a longer version of the
androgen receptor gene associated with
weaker signaling
Hare L, Bernard P, Sanchez FJ, Baird PN, Vilain E, Kennedy T, Harley VR. Androgen Receptor Repeat Length Polymorphism
Associated with Male-to-Female Transsexualism BIOLOGICAL PSYCHIATRY 65 (1): 93-96 (2009)
FtM transsexualism
– Gene variant for 17 α-Hydroxylase* causes
higher concentrations of androgens and
estrogen hormones in developing brain
*Also called cytochrome P17
Bentz, Eva-Katrin; Hefler, Lukas A.; Kaufmann, Ulrike; Huber, Johannes C.; Kolbus, Andrea; Tempfer, Clemens B. A Polymorphism of
the CYP17 Gene Related to Sex Steroid Metabolism is Associated With Female-to-Male But Not Male-to-Female Transsexualism
OBSTETRICAL & GYNECOLOGICAL SURVEY 63 (12) 775-777 (2008)
63. Biology of Sexual Orientation
Anthropological evidence - gay
people everywhere
“Gay people have a different
sensibility”
Sandra Witelson, PhD
Same-sex behavior in nearly all
animals
– Homosexuality & other sexually
variant behaviors in animals is
widespread
Bruce Bagemihl, BIOLOGICAL EXUBERANCE: ANIMAL
HOMOSEXUALITY AND NATURAL DIVERSITY, New York: St.
Martin's Press (1999)
– Examples of same-sex behavior can
be found in almost all species in the
animal kingdom — from worms to
frogs to birds — making the practice
nearly universal among animals
Bailey N, Zuk M. Same-sex sexual behavior and evolution TRENDS IN
ECOLOGY AND EVOLUTION 24:439-446 (2009)
64. Sexual Orientation & INAH3
• Volume of INAH3 in homosexual male did
not differ significantly from that of females
and was significantly smaller than in
typical males
• Other hypothalamic nuclei same in gay
and typical males
LeVay, S. A Difference In Hypothalamic Structure Between Heterosexual And Homosexual Men.
SCIENCE, 253: 1034–1037 (1991)
65. More Evidence For “Gay Brain”
Follow up study in humans confirms LeVay’s
finding that INAH3 volume (presynaptic nerve
endings) is related to sexual orientation
New finding: no difference in the INAH3
neuron number (postsynaptic neurons) based
on sexual orientation
Byne, William, Tobel, Stuart, Mattiace, Linda A., Lasco, Mitchell S., Kemether, Eileen, Edgar, Mark A., Morgello, Susan, Buchsbaum, Monte S., and Jones,
Liesl B. The Interstitial Nuclei of the Human Anterior Hypothalamus: An Investigation of Variation with Sex, Sexual Orientation, and HIV Status.
HORMONES AND BEHAVIOR, 40: 86-92 (2001)
INAH3 neuron number correlates with gender
identity while INAH3 volume correlates with
sexual orientation
Garcia-Falgueras & Swaab, D.F. A sex difference in the hypothalamic uncinate nucleus: relationship to gender identity. BRAIN 131:(12) 3115-7 (2008)
Gay sheep brains
– About 8% of rams are exclusively homosexual
– “Duplicated” LeVay’s work on INAH3 of humans
Roselli CE, Larkin K, Resko JA, Stellflug JN, Stormshak F. The volume of a sexually dimorphic nucleus in the ovine medial preoptic area/anterior
hypothalamus varies with sexual partner preference. ENDOCRINOLOGY 145:489-483 (2004)
66. Brain Has Neuronal Network For
Sexual Identity and Sexual Orientation
“The sex reversals in INAH3 and the
BSTc, that are at least partly independent
of adult sex hormone changes, may be
part of a complex neuronal network that is
structurally and functionally related to
gender identity and sexual orientation.”
Garcia-Falgueras & Swaab, D.F. A sex difference in the hypothalamic uncinate nucleus: relationship to gender
identity. BRAIN 131:(12) 3115-7 (2008)
67. Anterior Hypothalamus Is
Activated by Sex Pheromones
Activation of
Positron emission tomography Subject anterior
(PET scans) of anterior hypothalamus
hypothalamus while subjects
smell sex pheromones Heterosexual
EST
males
Heterosexual – activated by sex
pheromones of other sex
Homosexual
Homosexual – activated by sex males
AND
pheromones of same sex
Heterosexual
AND
AND = progesterone derivative 4,16-androstadien-3-one females
EST = estrogen-like steroid estra-1,3,5(10),16-tetraen-3-ol
Berglund H, Lindström P, Savic I. Brain response to putative pheromones in lesbian Homosexual
EST
women. PNAS 103:8269-8274 (2006) females
68. Genetics of Gayness/Lesbianism
Evidence for genetic markers* for gay men and
their gay brothers in the Xq28 region on the X
chromosome
*Markers are regions or sections of DNA that are the same among family members, suggesting the presence of a gene
Hamer, D. H., Hu, S., Magnuson, V. L., Hu, N., & Pattatucci, A. M. A. Linkage Between DNA Markers On The X Chromosome And Male Sexual
Orientation. SCIENCE, 261: 321-327 (1993)
Hu, S., Pattatucci, A. M., Patterson, C., Li, L., Fulker, D. W., Cherny, S. S., Kruglyak, L., & Hamer, D. H. Linkage Between Sexual Orientation
And Chromosome Xq28 In Males But Not In Females. NATURE GENETICS, 11: 248-256 (1995)
Findings are consistent with a genetic
hypothesis for lesbianism
– Lesbians had significantly higher rates of lesbian sisters,
daughters, and cousins through a paternal uncle than did
heterosexual women
Pattatucci, A. M. L., & Hamer, D. H. Development And Familiality Of Sexual Orientation In Females. BEHAVIOR GENETICS, 25: 407-420
(1995)
– Increasing rates of concordance of lesbianism from nonidentical
twins to identical twin pairs
Bailey, J. M., & Benishay, D. S. Familial aggregation of female sexual orientation. AMERICAN JOURNAL OF PSYCHIATRY, 150: 272-277
(1993)
Bailey, J. M., Dunne. M. P., & Martin, N. G. Genetic And Environmental Influences On Sexual Orientation And Its Correlates In An Australian
Twin Sample. JOURNAL OF PERSONALITY AND SOCIAL PSYCHOLOGY, 78: 524-536 (2000)
– But lesbianism is not associated with the locus at Xq28
Hu, S., Pattatucci, A. M., Patterson, C., Li, L., Fulker, D. W., Cherny, S. S., Kruglyak, L., & Hamer, D. H. Linkage Between Sexual Orientation
And Chromosome Xq28 In Males But Not In Females. NATURE GENETICS, 11: 248-256 (1995)
69. Summary -
Core
Sexuality
The scientific story explains everyone!
“The preponderance of evidence seems to
indicate that the theory of organization-
activation for the development of sexual
behavior is certain for non-human mammals
and almost certain for humans"
Milton Diamond. Clinical implications of the organizational and activational effects of hormones. HORMONES AND BEHAVIOR 55:621–632 (2009)
Pivotal work on human anterior hypothalamus:
LeVay, S. A Difference In Hypothalamic Structure Between Heterosexual And Homosexual Men. SCIENCE, 253: 1034–1037 (1991)
Zhou, J.N. Hofman, M.A. Gooren, L.J. and Swaab, D.F.. A Sex Difference in the Human Brain and its Relation to Transsexuality. NATURE, 378: 68-70
(1995)
Kruijver, Frank P. M., Zhou, Jiang-Ning, Pool, Chris W. Hofman, Michel A.,. Gooren, Louis J. G And Swaab, Dick F. Male-To-Female Transsexuals Have
Female Neuron Numbers In A Limbic Nucleus. J CLIN ENDOCRINOL METAB, 85: 2034-2041 (2000)
Garcia-Falgueras, Alicia, Swaab, Dick F. A Sex Difference In The Hypothalamic Uncinate Nucleus: Relationship To Gender Identity. BRAIN, (Nov 2,
2008)
70. Organization-Activation Theory
“The fetal brain develops during the
intrauterine period in the male direction
through a direct action of testosterone on
the developing nerve cells, or in the
female direction through the absence of
this hormone surge. In this way, our
gender identity (the conviction of
belonging to the male or female gender)
and sexual orientation are programmed or
organized into our brain structures when
we are still in the womb”
Garcia-Falgueras A, Swaab DF. Sexual hormones and the brain: an essential alliance for sexual identity and sexual orientation PEDIATRIC
NEUROENDOCRINOLOGY 17: 22-35 (2010)
71. Critical Periods of Genitalia
and Brain Are Different
“However, since sexual differentiation of the
genitals takes place in the first two months of
pregnancy and sexual differentiation of the brain
starts in the second half of pregnancy, these
two processes can be influenced independently,
which may result in extreme cases in
transsexuality.”
“This also means that in the event of ambiguous
sex at birth, the degree of masculinization of the
genitals may not reflect the degree of
masculinization of the brain.”
Garcia-Falgueras A, Swaab DF. Sexual hormones and the brain: an essential alliance for sexual identity and sexual orientation PEDIATRIC
NEUROENDOCRINOLOGY 17: 22-35 (2010)
72. Core Sexuality:
Nature - Not Nurture!
“There is no indication that social
environment after birth has an effect
on gender identity or sexual
orientation”
Garcia-Falgueras A, Swaab DF. Sexual hormones and the brain: an essential alliance for sexual identity and sexual orientation PEDIATRIC
NEUROENDOCRINOLOGY 17: 22-35 (2010)
73. Ancient Brain Regions
The Journal of Comparative Neurology. Vol 519, Issue 18, pages 3599-3639,
17 OCT 2011 DOI: 10.1002/cne.22735 http://onlinelibrary.wiley.com/doi/10.1002/cne.22735/full#fig3
74. Three Somatic Morphology (X axis)
Dimensions of Sexual Identity (Y axis)
Core Sexuality Sexual Orientation (Z axis)
Gynecentric
Androphilic
Gynemorphic Andromorphic
Everyone occupies a
Gynephilic point in this three-
dimensional space!
Androcentric
75. Every cell
has a sex!
Four
“transcriptional
sexes” in PBMC
– XX/no T
– XY/T
– XX/T
– XY/no T
*PBMC = peripheral blood mononuclear cells
Holterhus P-M, Bebermeier J-H, Werner R, Demeter J,
Richter-Unruh A, Cario G, Appari M, Siebert R,
Riepe F, Brooks JD, Hiort O. Disorders of sex
development expose transcriptional autonomy of
genetic sex and androgen-programmed hormonal
sex in human blood leukocytes BMC GENOMICS
10:292 (2009)
76. 4 Sexes!
157 genes
expressed
differently in
males vs.
females
– Sex chromosome
programming of 11
genes
– Androgen-
dependent
programming of
146 genes (not
affected by
circulating
hormones)
Holterhus P-M, Bebermeier J-H, Werner R, Demeter J, Richter-Unruh A, Cario G, Appari
M, Siebert R, Riepe F, Brooks JD, Hiort O. Disorders of sex development
expose transcriptional autonomy of genetic sex and androgen-programmed
hormonal sex in human blood leukocytes BMC GENOMICS 10:292 (2009)
77. Cellular Sex!
Intersex
people are
intersex in
every cell of
their bodies
No two people
alike
Holterhus P-M, Bebermeier J-H, Werner R, Demeter J, Richter-Unruh A, Cario G, Appari
M, Siebert R, Riepe F, Brooks JD, Hiort O. Disorders of sex development
expose transcriptional autonomy of genetic sex and androgen-programmed
hormonal sex in human blood leukocytes BMC GENOMICS 10:292 (2009)
78. Sex ≠ Gender
Sex is biological
Gender is cultural
Gender “traits” differ
from culture to culture
and from time to time Castor Semenya
Controversy over whether this
South African eighteen-year old
should be allowed to compete as
a woman continues
79. The “Gender Binary”
Welive in a “binary gendered” culture with two
genders only
– Woman
– Man
Many cultures recognize more than two genders
80. NORTH AMERICA
Two-spirits – Native American
Berdache – Illiniwek (Illinois)
Muxes – Zapotec People, Oaxaca, Mexico
Muxes
Two-spirits
Thanks to Lorelei Erisis
http://transprov.wordpress.com/2009/05/21/simple-list-of-third-gender-and-gender-variant-groups/
81. SOUTH AMERICA
Travestís – Brazil
Bichas
Viados
Guevedoche – Dominican Republic
Quariwarmi – Incan
Viados
Travestís
Thanks to Lorelei Erisis
http://transprov.wordpress.com/2009/05/21/simple-list-of-third-gender-and-gender-variant-groups/
82. EUROPE
The Sworn Virgin – Balkans Sworn Virgin
Catamites – Ancient Greece
Mollies – Modern England
Tertium genus hominum (a
third human gender)
“eunuchs” – Ancient Eastern
Mediterranean
Catamites Sworn Virgin
Thanks to Lorelei Erisis
http://transprov.wordpress.com/2009/05/21/simple-list-of-third-gender-and-gender-variant-groups/
83. AFRICA
Mashoga
Ashtime – Maale culture of Southern Ethiopia
Mashoga – Swahili-speaking areas of the
Kenyan coast, particularly Mombasa
Mangaiko – The Mbo people, Democratic
Republic of the Congo
Sḫt (”sekhet”) – Middle Kingdom of Egypt
(2000-1800 BCE)
Thanks to Lorelei Erisis
http://transprov.wordpress.com/2009/05/21/simple-list-of-third-gender-and-gender-variant-groups/
84. MIDDLE EAST
The Kurgarûs – Sumer
kur.gar.ra
ur.sal
Zenanas – Arab
Xanith or Khanith – Oman
Thanks to Lorelei Erisis
http://transprov.wordpress.com/2009/05/21/simple-list-of-third-gender-and-gender-variant-groups/
85. ASIA
Hijras
lyha – Mohave
Hijras – India, Pakistan & Bangladesh
also known as: Aravani/Aruvani or Jogappa
Hijira (alt. sp.) – India
Sādhi
Kotis
Sadhin – The Gaddhi in the foothills of the
Himalayas
Thanks to Lorelei Erisis
http://transprov.wordpress.com/2009/05/21/simple-list-of-third-gender-and-gender-variant-groups/
86. ASIA continued
Basivi – Madras (area of India)
Tritiya-prakrti (third-nature) – Indic Kathoey
culture of premodern India
Ubhatobyanjanakas – Buddhist Vinaya
Pandakas
Kathoey – Thailand
Pandaka – Ancient Buddhist Societies
Thanks to Lorelei Erisis
http://transprov.wordpress.com/2009/05/21/simple-list-of-third-gender-and-gender-variant-groups/
Kathoey
88. INDONESIA
Waria Waria
Kwolu-aatmwol – “Sambia” community in the
eastern highlands of Papua New Guinea
PHILIPPINES
bakla – Tagalog
Bayot – Cebuano
Agi – Ilonggo
Bantut – Tausug
Binabae
Bading
Lakin-on
Thanks to Lorelei Erisis
bakla
http://transprov.wordpress.com/2009/05/21/simple-list-of-third-gender-and-gender-variant-groups/
89. Disordered or Just Different?
Gender binary has permeated medicine
The medical profession has
pathologized and stigmatized gender-
variant peoples
– Lesbian, gay, bisexual people
– Transsexual people
– Intersex people
90. Medical Profession’s Treatment of LGBT People
1952 (DSM-I) Sociopathic Personality Disorders
1968 (DSM-II) Sexual Deviation
1970 Gay rights activists storm APA annual convention
1972 APA annual meeting –first-ever panel of non-
patient homosexuals” and Dr. Anonymous
1973 (DSM-II Revision) Deletion of Homosexuality
Substitution of Sexual Orientation Disturbance
(Homosexuality is not illness but supposedly discomfort with being persecuted as a homosexual is
an illness)
1980 (DSM-III) Gender Identity Disorder (GID)
Ego-dystonic Homosexuality (formerly SOD)
1987 (DSM-III Revision) Homosexuality omitted entirely
(Ego-dystonic homosexuality/SOD removed. It’s normal to not want to be persecuted & empirical
data to support diagnosis is lacking))→
2000 (APA Position Statement) Ethical psychiatrists should stop conversion or
“reparative therapies”
Homosexuality was removed from the list of mental disorders by the World Health Organisation in 1990
91. Intersex Problems: Socio-cultural
“The basic problems faced by the
intersexed are socio-cultural in nature
and not medical and are a result of the
dogmatic fundamentalism inherent in
the current binary construct of sex and
gender”
“Some intersexed individuals are
subjected to genital mutilation in
childhood as a result of this Curtis Hinkle - Founder
totalitarian, sexist oppression”
Organization Intersex International
http://www.gopetition.com/petitions/solidarity-with-the-intersex-community.html
Whatever happened to
“informed consent?”
Whatever happened to
“first, do no harm?”
Sharon E. Preves. INTERSEX and IDENTITY The Contested Self Rutgers University Press (2003)
92. Genital “Normalization” Surgery - Dismal Outcomes
Migeon; CJ, Wisniewski, AB, Gearhart JP, Meyer-Bahlburg, HFL, Rock, JA, Brown, TR, Casella, SJ, Maret A, Ngai KM, Money J, Berkovitz GD. Ambiguous
Genitalia With Perineoscrotal Hypospadias in 46,XY Individuals: Long-Term Medical, Surgical, and Psychosexual Outcome PEDIATRICS 110:10p
(2002)
Kohler B, Kleinemeier E, Lux A, Hiort O, Gruters A, Thyen U, DSD Network Working Group. Satisfaction with genital surgery and sexual life of adults with
XY disorders of sex development: results from the German clinical evaluation study. CLIN ENDOCRINOL METAB 97(2):577-88 (2012)
Researchers never asked: What if we did nothing?
93. NEW STANDARDS OF CARE American Academy British Association Pediatric
FOR Pediatricians Surgeons
INTERSEX PATIENTS year 2000 year 2001
Diamond, M. Sex, gender, and identity over the years: a changing
perspective CHILD AND ADOLESCENT PSYCHIATRIC CLINICS
OF NORTH AMERICA 13:591-607 (2004) No surgical moratorium
#1. General moratorium on sex (In1999, AAP decided that surgical
moratorium was “unrealistic” because it No surgical moratorium
assignment cosmetic surgery was hypothesized that parents would not
accept it)
#2. Moratorium should not be Recognized need for more Recognized need for more
lifted unless and until studies research and greater candor research and greater candor
show outcomes are positive and honesty and honesty
#3. Efforts should be made to No call back to families or No call back to families or
undo effects of past physician individuals that had previous individuals that had previous
deception and secrecy treatment treatment
Informed consent includes
Response to intersex birth “Social emergency” “possibility of non-operative
management”
All virilized females (CAH or
Gender assignment on
maternal androgen) should be
Gender assignment individual basis; may include
girls (because of retained
cultural considerations
fertility)
Infants raised as girls “will “There is a strong case for no
Clitoral surgery usually require clitoral clitoral surgery in lesser
reduction” degrees of clitoromegaly”
PAIS infants “in whom a very
small phallus mandates a The risk of malignant testicular
Penile surgery
female sex of rearing” should changes in AIS is small
have testes removed
94. 2006 Pediatric Consensus Statement
“Disorders of Sexual Development” – new term
– Rather than “Differences” or “Variations”
“Sexual identity issue” is dismissed
– “Structure of the brain is not currently useful for gender
assignment”
Parental distress & prejudice used to justify
damaging surgery
Gender assignment decisions are still made using
“scientifically inappropriate” factors
– Diagnosis
– Genital appearance
– Surgical options
– Need for lifelong replacement therapy
– Potential for fertility
– Views of family
– Circumstances relating to cultural practices
Collaboration with participants in International Consensus Conference on Intersex organized by Lawson Pediatric Endocrine Society and European
Society for Paediatric Endocrinology
Lee PA, Houk CP, Ahmed SF, Hughes IA. Consensus statement on management of intersex disorders PEDIATRICS 118:488-500 (2006)
95. Malpractice Continues
Clitoral reduction – still “standard clinical
procedure”
Dr. Dix P. Poppas, Panel at Weill Cornell Medical College http://www.cornellsun.com/section/news/content/2010/10/05/weill-medical-college-
says-poppas%E2%80%99-surgical-procedure-standard
Attempts to prevent same-sex attraction and
tom-boy behavior in CAH girls
(Treat pregnant women with dexamethasone)
http://www.starobserver.com.au/news/2010/07/15/opposition-to-genital-drugs/27947
Over 50% are misdiagnosed!
Minto CL, Crouch NS, Conway GS, Creighton SM. XY females: revisiting the diagnosis BJOG: an International Journal of Obstetrics and Gynaecology 112:1407–1410
(2005)
Current DSM-5 proposal: Gender Dysphoria
with a DSD!
http://ajp.psychiatryonline.org/article.aspx?articleID=1268265
LGBTI people have their own health concerns
that are not being addressed
Holterhus P-M, Bebermeier J-H, Werner R, Demeter J, Richter-Unruh A, Cario G, Appari M, Siebert R, Riepe F, Brooks JD, Hiort O. Disorders of sex
development expose transcriptional autonomy of genetic sex and androgen-programmed hormonal sex in human blood leukocytes BMC GENOMICS
10:292 (2009)