INTERSEX PEOPLE: Who Are They? Presented By Veronica Drantz, PhDAnd Intersex Spokespersons Alex & Chrixs Prepared for Argosy University A2Z March 23, 2013
Famous Intersex People Carolyn Cossey XXXY (Klinefelter’s) Julia Child XY (CAIS) Caster Semenya (CAIS?)
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)
The Myth: “The Gender Binary” Gametes are binary (eggs or sperm) Organisms that make the gametes are not binary!
23 Pairs Human Chromosomes XX (Female), XY (Male)Figure 25-2 Karyotype of chromosomes from a normal male. The chromosomes havebeen stained with Giemsas stain, which produces a characteristic banding pattern.
Genetic Sex Determination • Typical male has Y chromosome • Typical female has no Y chromosomeFigure 25-1 Basis of genetic sex determination. In the two-stage meiotic division in the female, only one cell survives as themature ovum. In the male, the meiotic division results in the formation of four sperms, two containing the X and two the Ychromosome. Fertilization thus produces a male zygote with 22 pairs of autosomes plus an X and a Y or a female zygote with22 pairs of autosomes and two X chromosomes. Note that for clarity, this figure and Figures 25–6 and 25–7 differ from thecurrent international nomenclature for karyotypes, which lists the total number of chromosomes followed by the sexchromosome pattern. Thus, XO is 45, X; XY is 46, XY; XXY is 47, XXY, and so on.
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
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 differentiationhttp://quizlet.com/3597081/x-and-y-chromosomes-flash-cards/
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
“Organization – Activation” Mechanism “Prenatal hormone theory” – Organization before birth – Activation at puberty
SexualDifferentiation of Internal GenitaliaFigure 25-4 Embryonicdifferentiation of male andfemale internal genitalia(genital ducts) fromwolffian (male) andmüllerian (female)primordia.
SexualDifferentiation ofExternal GenitaliaFigure 25-5 Differentiation of maleand female external genitalia fromindifferent primordial structures in theembryo.
Sexual Development in MammalsFigure 25-6 Diagrammatic summary of normal sex determination, differentiation, anddevelopment in humans. MIS, müllerian inhibiting substance; T, testosterone; DHT,Dihydrotestosterone
Androgen Hormones Are Madein Adrenal Glands and Gonadshttp://www.carolguze.com/text/442-6-sexual_differentiation.shtml 17β-HSD=17-beta hydroxysteroid dehydrogenase
Male Testosterone LevelsFigure 25-8 Plasma testosterone levels at various ages inhuman males.
Mechanism of Steroid Hormone Action BrainFigure 25-18 Schematic diagram of the actions of testosterone (solid arrows) and dihydrotestosterone (dashed arrows).
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 PenisLabioscrotal swellings Scrotum Urogenital folds Urethra
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
Activation at Puberty Tanner scaleshttp://upload.wikimedia.org/wikipedia/commons/thumb/0/0c/Tanner_scale-female.svg/240px-Tanner_scale-female.svg.pnghttp://upload.wikimedia.org/wikipedia/commons/8/8f/Tanner_scale-male.png
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
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”
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)
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)
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
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
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)
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
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 IColapinto, John. As Nature Made Him - The Boy Who WasRaised 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)
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!
Intersex People Curtis Hinkle - Founder Organization Intersex International
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)
Sex Has Many LevelsPrimary sexcharacteristic 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
Translocation of SRY Unequal gene from Y to X Crossing-over chromosome – XY FemaleBetween 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
Variations of Genetic Sexes Nondisjunction of chromosomes during meiosis in parent’s gonadhttp://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
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 abnormalitiesLuria, Z., Friedman, S., andRose, M.D. HUMAN SEXUALITY.New York: John Wiley & Sons – No maturation at puberty(1987)
Klinefelter Syndrome Karyotype 47XXY Most common sex chromosome disorder (1 or 2 cases/1000) Male phenotype Hypogonadismhttp://www.aurorahealt Seminiferous tubule dysgenesishcare.org/yourhealth/healthgate/images/si55551770.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)
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 XXXYShirley Ratcliffe Arch Dis Child 1999;80:192–195
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
Brain AndrogenInsensitivity 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)
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.
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)
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 amastectomy, cut my hair short and lived as a celibate man. It wouldactually 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
Partial AIS & Gender Identity18 subjects:•Often ambivalent about assigned gender•67% believed that the gender in which they were raised was best for them, whereas theothers 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 sincepuberty**Attempted before switchingDiamond, Milton and Watson, Linda Ann. “Androgen insensitivity syndrome and Klinefelter’s syndrome: sexand gender considerations” Child Adolesc Psychiatric Clin N Am 13 (2004) 623—640
Five Degrees of Virilization Affecting the Urogenital Sinus and External Genitalia in FemalesHines M, Brook C., Conway, G.S. Androgen And Psychosexual Development Core Gender Identity, Sexual Orientation AndRecalled Childhood Gender Role Behavior In Women And Men With Congenital Adrenal Hyperplasia (CAH). J SEX RES, 41: 75-81(2004)
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 CLINICALSons (1987) MEDICINE. England: Mosby-Wolfe (1993)
Frequency of CAHFigure 4. Frequency of nonclassical and classical 21-hydroxylase deficiency in comparison with other autosomal recessive disease incidencesHines 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)
CAH (Adrenogenital Syndrome) Luria, Z., Friedman, S., and Rose, M.D. HUMAN SEXUALITY. New York: John Wiley & Sons (1987)
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 Womens 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),
Hypospadias These common conditions are often not regarded as intersex condition. But they are!
Figure 4.Metabolism of Testosterone to 5_-Dihydrotestosteroneby 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
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 absenceof the penis neonatal assignmentgreen arrows: everted bladder; to female sex hasblue arrows: the scrotum; been advocated foryellow arrows: umbilcal cord affected males
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 storyReiner, 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)
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 SexNetter, Frank H. The CIBA COLLECTION OF MEDICALILLUSTRATIONS. Vol I. Nervous System. Part I. Anatomy &Physiology. New York: CIBA (1983)
Sexual Behavior and GonadalFunction 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
Biology of Sexual Identity FaafafineA broadly accepted social class in Samoa
Bed Nucleus of the Stria TerminalisFigure 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
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 transsexualKruijver, 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)
Genetics of Transsexuality MtF transsexualism – Significant link with a longer version of the androgen receptor gene associated with weaker signalingHare 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 P17Bentz, 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)
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 widespreadBruce Bagemihl, BIOLOGICAL EXUBERANCE: ANIMAL HOMOSEXUALITY AND NATURAL DIVERSITY, New York: St. Martins 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 animalsBailey N, Zuk M. Same-sex sexual behavior and evolution TRENDS IN ECOLOGY AND EVOLUTION 24:439-446 (2009)
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 malesLeVay, S. A Difference In Hypothalamic Structure Between Heterosexual And Homosexual Men. SCIENCE, 253: 1034–1037 (1991)
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 orientationByne, 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 orientationGarcia-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 humansRoselli 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)
Brain Has Neuronal Network ForSexual 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)
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 ANDAND = progesterone derivative 4,16-androstadien-3-one femalesEST = estrogen-like steroid estra-1,3,5(10),16-tetraen-3-olBerglund H, Lindström P, Savic I. Brain response to putative pheromones in lesbian Homosexual EST women. PNAS 103:8269-8274 (2006) females
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 geneHamer, 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 womenPattatucci, 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 pairsBailey, 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 Xq28Hu, 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)
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)
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 PEDIATRICNEUROENDOCRINOLOGY 17: 22-35 (2010)
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)
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)
Ancient Brain RegionsThe 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
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
Every cell has a sex! Four “transcriptional sexes” in PBMC – XX/no T – XY/T – XX/T – XY/no T*PBMC = peripheral blood mononuclear cellsHolterhus 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)
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)
Cellular Sex! Intersex people are intersex in every cell of their bodies No two people alikeHolterhus 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)
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
The “Gender Binary” Welive in a “binary gendered” culture with two genders only – Woman – Man Many cultures recognize more than two genders
NORTH AMERICA Two-spirits – Native American Berdache – Illiniwek (Illinois) Muxes – Zapotec People, Oaxaca, Mexico Muxes Two-spiritsThanks to Lorelei Erisishttp://transprov.wordpress.com/2009/05/21/simple-list-of-third-gender-and-gender-variant-groups/
SOUTH AMERICA Travestís – Brazil Bichas Viados Guevedoche – Dominican Republic Quariwarmi – Incan Viados TravestísThanks to Lorelei Erisishttp://transprov.wordpress.com/2009/05/21/simple-list-of-third-gender-and-gender-variant-groups/
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/
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 Erisishttp://transprov.wordpress.com/2009/05/21/simple-list-of-third-gender-and-gender-variant-groups/
MIDDLE EAST The Kurgarûs – Sumer kur.gar.ra ur.sal Zenanas – Arab Xanith or Khanith – OmanThanks to Lorelei Erisishttp://transprov.wordpress.com/2009/05/21/simple-list-of-third-gender-and-gender-variant-groups/
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 HimalayasThanks to Lorelei Erisishttp://transprov.wordpress.com/2009/05/21/simple-list-of-third-gender-and-gender-variant-groups/
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
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/
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
Medical Profession’s Treatment of LGBT People1952 (DSM-I) Sociopathic Personality Disorders1968 (DSM-II) Sexual Deviation1970 Gay rights activists storm APA annual convention1972 APA annual meeting –first-ever panel of non- patient homosexuals” and Dr. Anonymous1973 (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
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)
Genital “Normalization” Surgery - Dismal OutcomesMigeon; 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?
NEW STANDARDS OF CARE American Academy British Association Pediatric FOR Pediatricians Surgeons INTERSEX PATIENTS year 2000 year 2001Diamond, M. Sex, gender, and identity over the years: a changingperspective CHILD AND ADOLESCENT PSYCHIATRIC CLINICSOF 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
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)
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 addressedHolterhus 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)