1.
What Is a Female? A Male? <ul><li>Primary sex characteristic </li></ul><ul><ul><li>Type of gonads </li></ul></ul><ul><ul><ul><li>Female gonad is ovary – produces eggs </li></ul></ul></ul><ul><ul><ul><li>Male gonad is testis – produces sperm </li></ul></ul></ul><ul><ul><li>Develop in fetus </li></ul></ul><ul><ul><li>Testosterone & its derivatives are “directional” </li></ul></ul><ul><li>Secondary sex characteristics </li></ul><ul><ul><li>Produced by gonadal hormones </li></ul></ul><ul><ul><ul><li>Androgens </li></ul></ul></ul><ul><ul><ul><li>Estrogens </li></ul></ul></ul><ul><ul><li>Develop during puberty </li></ul></ul><ul><ul><li>Hormones are “activational” </li></ul></ul>

2.
Sex Has Many Levels <ul><li>Genetic Sex - Chromosomes </li></ul><ul><li>Gonadal Sex – Ovaries or Testis </li></ul><ul><li>Somatic Sex – Body anatomy/physiology </li></ul><ul><li>Psychological Sex - Sexual identity </li></ul><ul><li>and then there is </li></ul><ul><li>Sexual orientation </li></ul>

3.
Intersexuality <ul><li>Incidence: 1.7%*- 2.5% </li></ul><ul><li>Intersexual people are as natural as the rest of us </li></ul><ul><li>They are nature’s experiments to a physiologist – providing information about sexual development </li></ul><ul><li>Only in recent years have we been able to track intersexual people over their lifetime and find out about their sexual identity and orientation </li></ul><ul><li>They illustrate how no definition of female or male is always “satisfying” </li></ul><ul><li>* Fausto-Sterling, Anne. SEXING THE BODY: GENDER POLITICS AND THE CONSTRUCTION OF SEXUALITY. Basic Books (2000) </li></ul>

4.
Ganong, William F. REVIEW OF MEDICAL PHYSIOLOGY 22 nd ed. Lange Medical Books/McGraw-Hill (2005)

5.
How to Treat a Newborn With Ambiguous Genitalia or Mutilated Penis?

6.
John Money Psychologist <ul><li>Psychosexual &quot;neutrality-at-birth&quot; theory </li></ul><ul><ul><li>Postulate 1: Individuals are psychosexually neutral at birth </li></ul></ul><ul><ul><li>Postulate 2: Healthy psychosexual development is intimately related to the appearance of the genitals </li></ul></ul>

7.
Milton Diamond Biologist <ul><li>“ Sexuality-at-birth&quot; theory </li></ul><ul><ul><li>Theory of psychosexual predisposition </li></ul></ul><ul><ul><li>Inherent sexuality provides a built-in &quot;bias&quot; with which the individual interacts with his environment </li></ul></ul><ul><ul><li>Prenatal genetic and hormonal influences predispose at birth to a male or female gender orientation </li></ul></ul><ul><ul><li>Sexual behavior of an individual, and thus gender role, are not neutral and without initial direction at birth </li></ul></ul><ul><li>Diamond challenges Money </li></ul><ul><li>Diamond M. A Critical Evaluation Of The Ontogeny Of Human Sexual Behavior. QUARTERLY REVIEW OF BIOLOGY, 40: 147–175 (1965) </li></ul><ul><li>The John / Joan case </li></ul><ul><li>Diamond, Milton. And Sigmundson, H. Keith. Sex Reassignment at Birth: A Long Term Review and Clinical Implications. ARCHIVES OF PEDIATRIC & ADOLESCENT MEDICINE, 151: 298-304 (1997) </li></ul><ul><li>Money’s view is now discredited! </li></ul>

8.
Chromosomal Variants of Sexes 1/500 of the population have a karyotype other than XX or XY. Intersex Support Group International (1999-2001) Ganong, William F. REVIEW OF MEDICAL PHYSIOLOGY 22 nd ed. Lange Medical Books/McGraw-Hill (2005)

9.
Variations of Genetic Sexes <ul><li>Nondisjunction of chromosomes </li></ul><ul><ul><li>XO Female (Turner Female) </li></ul></ul><ul><ul><li>XXX Female (Superfemale) </li></ul></ul><ul><ul><li>XXY, XXXY etc. Male (Klinefelter Male) </li></ul></ul><ul><ul><li>XYY Male (Jacob’s Syndrome) </li></ul></ul><ul><li>Translocation of SRY gene from Y to X chromosome </li></ul><ul><ul><li>XY Female (Swyer syndrome): absence or mutation of SRY on Y produces females with gonadal dysgenesis </li></ul></ul><ul><ul><li>XX Male (XX Male Syndrome): SRY gene in one or both X chromosomes, produces infertile males </li></ul></ul>

10.
Turner’s Syndrome <ul><li>Karyotype is 44 autosomes plus XO </li></ul><ul><li>Ovarian agenesis or gonadal dysgenesis </li></ul><ul><ul><li>Gonads rudimentary or absent </li></ul></ul><ul><ul><li>Female external genitalia </li></ul></ul><ul><ul><li>Short stature, other congenital abnormalities </li></ul></ul><ul><ul><li>No maturation at puberty </li></ul></ul>Luria, Z., Friedman, S., and Rose, M.D. HUMAN SEXUALITY. New York: John Wiley & Sons (1987)

11.
Turner’s Syndrome Forbes, C.D. and Jackson, W.F. A COLOUR ATLAS AND TEXT OF CLINICAL MEDICINE. England: Mosby-Wolfe (1993)

12.
Klinefelter Syndrome <ul><li>Karyotype 47XXY </li></ul><ul><li>Most common sex chromosome disorder (1 or 2 cases/1000) </li></ul><ul><li>Male phenotype </li></ul><ul><li>Hypogonadism </li></ul><ul><li>Seminiferous tubule dysgenesis </li></ul><ul><ul><li>Reduced or absent spermatogenesis </li></ul></ul><ul><ul><li>Variability in presentation is related mainly to the timing and amount of androgen deficiency </li></ul></ul><ul><ul><li>Increased FSH levels (indicates low inhibin B from Sertoli cells) </li></ul></ul><ul><ul><li>The more supernumerary sex chromosomes that exist, the more likely are detrimental physical and mental findings </li></ul></ul><ul><ul><li>Cryptorchidism 3X more frequent </li></ul></ul><ul><ul><li>Taller, greater leg growth ( 5 and 8 years) </li></ul></ul><ul><ul><li>Tendency for central obesity </li></ul></ul><ul><ul><li>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 </li></ul></ul><ul><ul><li>Gynecomastia 30% to 90% of cases </li></ul></ul><ul><ul><li>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 </li></ul></ul><ul><ul><li>Fertility becomes increasingly doubtful as age advances; however, before infertility is predicted, sperm analysis is required because paternity has been documented </li></ul></ul>Forbes, C.D. and Jackson, W.F. A COLOUR ATLAS AND TEXT OF CLINICAL MEDICINE. England: Mosby-Wolfe (1993)

13.
Klinefelter Syndrome & Gender Expression <ul><li>Infrequently discussed in medical descriptions of KS are individuals’ concerns with gender expressions and feelings </li></ul><ul><li>An unknown percentage of persons who have KS experience androgynous or feminine feelings that can develop at an early age </li></ul><ul><li>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 </li></ul><ul><ul><li>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 </li></ul></ul><ul><ul><li>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 </li></ul></ul>

14.
KS Subjects Are Gynephilic! <ul><li>KS subjects are gynephilic! ”Homosexuality” among KS males was not found or the prevalence was not any different from that seen in the general population ( Shirley Ratcli ff e Arch Dis Child 1999; 80 :192–195) </li></ul><ul><li>Note: This indicates that sexual orientation region(s) of brain have been “altered.” Significantly, XXY fetal prenatal and postnatal testosterone levels do not differ from XY controls – so testosterone is available to “alter” hypothalamic and other brain regions during development of KS brain </li></ul>

15.
Comparison of XYYs and XXYs Sex Roles <ul><li>Similarities far outweigh the differences except for sex roles </li></ul><ul><li>XXY has more problems with masculine role </li></ul><ul><ul><li>Appear less masculine </li></ul></ul><ul><ul><li>More submissive and dependent </li></ul></ul><ul><ul><li>Drawings show less sex-differentiation </li></ul></ul><ul><ul><li>Ratcliffe, Shirley. Long Term Outcome In Children Of Sex Chromosome Abnormalities. ARCH DIS CHILD; 80:192–195 (1999) </li></ul></ul>

16.
Why Do Many of These KS “Men” Identify As Androgynous or Women? <ul><li>My tentative answer </li></ul><ul><li>Research evidence for expression of genes on sex chromosomes in early brain development </li></ul><ul><li>XX and XY embryonic rodent brains develop differently before gonads develop (so hormone influence is not a factor) </li></ul><ul><li>Dewing, P., Shi, T., Horvath S., and Vilain, E. Sexually Dimorphic Gene Expression in Mouse Brain Precedes Gonadal Differentiation. MOLECULAR BRAIN RESEARCH, 118: 82-90 (2003) </li></ul><ul><li>Carruth, Laura L., Reisert, Ingrid, and Arnold, Arthur P. Sex Chromosome Genes Directly Affect Brain Sexual Differentiation. NATURE NEUROSCIENCE, 5: 933-934 (2002) </li></ul>