1. Sexual Development and Sexuality
William McNett, MD
Associate Professor of Pediatrics
Jefferson Medical College
A.I. duPont Hospital for Children
December 15,2015

2. Clinical Case
3 ½ yr old male is fascinated with Disney Princesses, plays dress up frequently. Physically healthy. Product of a full term, uncomplicated pregnancy
Non-verbal gender expression fluctuated between genders
At 5 yrs, expresses that God made a mistake and gave her a penis, when will it go away?

3. Goals and Objectives Understand the development of Sex Characteristics
Learn Disorders of Sex Development and Initial Therapeutic Approach
Understand gender and sexual orientation development

4. Goals
Know the physical changes associated with puberty (Sexual Maturity Rating)
Understand the basis of evaluation and treatment of Disorders of Sex Development
Know the basis of gender identity and sexual orientation

5. Physical Sex Development
Embryological
Genitalia
Brain Development
Infant/Childhood
Puberty
Pre-pubescence
Pubescence
Post-pubescence

6. Embryologic Sex differentiation Occurs by 7th week
Y chromosome essential for testicular development
Wolffian ducts
Sertoli Cells: Mullerian Inhibitory Factor
Leydig Cells: Testosterone
Lack of Y chromosome essential for ovarian development
Mullerian ducts develop into uterus and fallopian tubes
Female sexual development does not depend on presence of ovaries (default setting)

7. Embryonic Sex organs Sexual Differentiation of the Brain
External sex organs fully formed by 12th week
Testes descend from posterior abdominal wall to deep inguinal ring by 28th week
Sexual Differentiation of the Brain
Occurs after the 20th week of gestation
High levels of testosterone in male fetus and continues through first three months of life
Combination of genes, sex hormones, and developing brain cells

8. Undifferentiated Sex Organ
gt: genital tuber
uf: urogenital fold
gs: gonadal sac

9. Embryonic Male Organ gt: genital tuber (penis) sf: scrotal fold
*: urethral groove

10. Physical sex development: Infant/Childhood
External sex characteristics don’t change until pre-pubescence
Hypothalamic-pituitary-gonadal axis is dormant
Low levels of sex hormones

11. Puberty: Pre-pubescence
Gonadotropin and sex steroids are still low but on the rise
Gonadotropin Releasing Hormone (GnRH) stimulates Luteinizing Hormone (LH) which stimulates ovaries or testes
Secondary sex characteristics begin to appear
Girls: growth spurt begins, pelvic girdle widens, breast start developing, pubic hair begins to appear, axillary hair begins to appear
Boys: growth spurt begins, voice begins to change, testicles begin to enlarge, pubic hair begins to appear, axillary hair begins to appear
Some behavioral changes

12. Puberty: Pubescence Reproductive organs become functional
Secondary sex characteristics become more apparent and adult
Significant behavior changes

13. Puberty: Post-pubescence
Skeletal maturation occurs
Males mature slower (18 yrs) then females (15 yrs)
Secondary sex characteristics
Females: is completed soon after onset of menses
Males: hair growth continues: extend up linea alba, beard growth, body hair growth, increase muscle mass through most of teen years

14. Sexual Maturation Rating Male Genitalia (Tanner Stage)
Preadolescent- testes, scrotum, and penis are similar in size to early childhood
Stage 2
Testes and scrotum are enlarged, scrotum skin shows change in texture
Stage 3
Penis has enlarged, mainly in length, testes and scrotum continue to enlarge
Stage 4
Penis is further enlarged in length and breadth with development of glans, scrotal skin becomes darker
Stage 5
Penis is adult in size, no further growth occurs

15. Sexual Maturation Rating Male Pubic Hair (Tanner Stage)
Preadolescent, no hair
Stage 2
Sparse growth of long, slightly pigmented, straight hair (vellus) above base of penis
Stage 3
Hair is darker, coarser, curlier, spreads sparsely over pubis
Stage 4
Hair is adult in type but covers less area then an adult
Stage 5
Hair is adult type, in inverse triangle, spreads to medial surface of the thighs

16. Sexual Maturation Rating Female, Breasts (Tanner Stage)
Preadolescent, elevation of papilla (nipple)
Stage 2
Breast bud stage- elevation of breast and papilla, areolar slightly enlarges
Stage 3
Further enlargement of breast and areolar, with no separation of their contours
Stage 4
projection of areolar and papilla to form a secondary mound above the level of the breast
Stage 5
Mature stage, papilla projection only. Recession of areolar to general contour of breast

17. Sexual Maturation Rating Female, Pubic Hair (Tanner Stage)
Preadolescent, no hair
Stage 2
Sparse growth of long, slightly pigmented, straight hair on labia majora
Stage 3
Hair is darker, coarser, curlier, spreads sparsely over labia
Stage 4
Hair is adult in type but covers less area then an adult
Stage 5
Hair is adult type, in inverse triangle, spreads to medial surface of the thighs

18. Sequence of Development
Males (9-17 yrs)
Testicular growth
Pubarche- onset of pubic hair
Penile growth
Peak height velocity
Females (8-16 yrs)
Breast budding
Pubarche- onset of pubic hair
Peak height velocity
Menarche (average age is 12.5, typically when Tanner 4)

19. Puberty Time Line: Male

20. Puberty Time Line: Female

21. Abnormal Sex Development
Precocious Puberty
Disorders of Sex Development

22. Precocious Puberty
Any pubertal changes if less then 8 yrs in females, 9 yrs in males
Types
Central resulting in Hypothalamic-pituitary-gonadal axis stimulation (Gonadotropin Releasing Hormone)
Starts entire puberty process including maturation of sex organs/fertility
Results in short stature due to premature closing of growth plates in long bones
Pseudoprecocious puberty- release of sex hormones
Premature thelarche (breast development)
Premature adrenarche (pubic hair, axillary hair, or body odor)

23. Precocious Puberty
Age 3 11/12 yrs, 5 8/12 yrs, 8 ½ yrs

24. Causes of Precocious Puberty
Central
Idiopathic
Hypothalamic hemartoma
Brain tumor
Brain insult: trauma, meningitis, hydrocephalus
Hypothyroidism
Pseudoprecocious or peripheral
idiopathic
Sex hormone secreting tumor (adrenals, testes, ovaries)
McCune-Albright Syndrome
Congenital Adrenal Hyperplasia
Exogenous estrogen or testosterone

25. Treatment of Precocious Puberty
Determine and treat underlying cause
If idiopathic, use of Gn RH antagonist
Desensitizes gonadotropin cells in pituitary
Monthly injection, very effective
Determine with family when to allow puberty to progress
If slow progression, may monitor bone age and allow to progress
Assess psycho-social concerns with family

26. Disorders of Sex Development
Potential for mischief at anytime in the embryonic development
Nomenclature changes: previously referred to as intersex, hermaphrodite, and ambiguous genitalia
Determined by chromosomal analysis
Described by chromosome and sex organs ( i.e. ovotesticular 46/XY)

27. Disorders of Sex Development
Clitoromegaly , posterior labial fusion
Hypospadias and scrotal fusion

28. Disorders of Sex Development
Penile hypospadias, chordee, and absent testicles
Partial androgen insensitivity, 46 XY

29. Disorders of Sex Development

30. Classification of DSD

31. Work up of Infant with DSD
Chromosomes Analysis
Sex hormone levels are usually not helpful
Radiographic- Assessing for sex organs: testes, ovaries, uterus, vagina
Ultrasound
Abdominal MRI
Genitogram (dye study)

32. Treatment of DSD Challenges Multi-discipline
Psycho-social dilemma for families
Multi-discipline
Pediatrician, endocrinologist, urologist, gynecologist, psychiatrist, family therapist
Consider delaying definitive treatment (surgery)
Hormone therapy, when reaching puberty

33. Incompletely Viralized Male, 46 XY 5α-reductase deficiency

34. Congenital Adrenal Hyperplasia Karyotype 46 XX, elevated 17-Hydroxyprogesterone

35. Healthy 6 month old infant

36. Androgen Insensitivity Syndrome, Karyotype 46 XY (Previously called Testicular Feminization)

37. Sexual Behavior Sex identity Gender identity
Anatomy based: Vagina or Penis
Gender identity
Female or Male
Physiology: typically determines gender
Culture: system of rules/customs dictates behavior
Sexual identity/Orientation
Fantasy/Arousal
Behavior
Culture
Developmental Goal
To be able to form loving and satisfying sexual relationships that benefit self and partner

38. Origin of Sexual Orientation and Gender Identification
Amount of Testosterone exposure in utero
Impact on genitalia development
Impact on brain development
Threshold necessary in XY to establish attraction to women
Illustrated by CAH on XX,46
Physical differences in areas of the hypothalamus
Genetic component
Twin studies
No ‘gay’ gene identified
Different models: epigenetic
Lack of evidence involving environmental factors

39. Theoretical model illustrating how fluctuations around an average concentration of testosterone (T) during embryonic life could lead to a homosexual or heterosexual orientation.
Theoretical model illustrating how fluctuations around an average concentration of testosterone (T) during embryonic life could lead to a homosexual or heterosexual orientation.
Balthazart J Endocrinology 2011;152:
©2011 by Endocrine Society

40. Gender Identity Disorder
Gender evolves from a combination of physiology and culture, but mostly physiology
Children learn to master and internalize system
Think about accepting androgyny as an alternative to GID

41. DSM-IV Criteria for GID
Strong and persistent cross-gender identification
Persistent discomfort with his or her sex or sense of inappropriateness in the gender role of that sex
Disturbance is not concurrent with Developmental Sex Disorder
Disturbance causes clinically significant distress or impairment in important areas of functioning

42. Gender Identity Disorder
Often onset is during preschool age
Is brought to medical attention in early school age
Is brought to medical attention when:
Parents realize behavior is not transient
Becomes source of concern or embarrassment
Causes deteriorating social relationships
Long term outcomes
no data for women
65% identify as gay men,10% transgender, 25% heterosexual
Clinical treatment
No evidence that actions will alter sex/gender identity pathway
Support, foster strengths, model behavior
Demystify through discussion: sibs, extended family

43. Resources
Sexual differentiation of the human brain in relation to gender identity and sexual orientation. Savic I, Garcia-Falgueras A, Swaab DF. Prog Brain Res. 2010;186:41-62.
Sexual orientation in women with classical or non-classical congenital adrenal hyperplasia as a function of degree of prenatal androgen excess. Meyer-Bahlburg H, Dolezal C, Baker S, New M Arch Sex Behav : 85-99
Homosexuality via canalized sexual development: A testing protocol for a new epigenetic model. Rice W, Friberg U, Gavrilets S. Bioessays 35:
Sexual differentiation of the human brain: Relation to gender identity, sexual orientation, and neuropsychiatric disorders. Bao A, Swaab D. Frontiers in Neuroendocrinology 32 (2011)

44. Questions

45. Test Question Sample
The following is the TYPICAL sequence for males progressing through puberty:
A: breast bud development, axillary hair growth, emotional lability, masturbates 5 times a day
B: testes enlargement, pubic hair development, penis length growth, ht growth velocity
C: pubic hair development, testes enlargement, ht growth velocity, penis length growth
D: testes enlargement, penis length growth, pubic hair development, ht growth velocity

46. Answer: B

47. Sequence of Development
Males (9-17 yrs)
Testicular growth
Pubarche
Penile growth
Peak height velocity
Females (8-16 yrs)
Breast budding
Pubarche
Peak height velocity
Menarche (average age is 12.5, typically when Tanner 4)

48. My Proposal Pizza