- UBC Urology Rounds

2012$12$13&
SEXUAL
DIFFERENTIATION:
ORDER AND DISORDER
Chuck Metcalfe, PGY 5
University of British Columbia
Department of Urologic Sciences
Urology Grand Rounds
December 12, 2012
OBJECTIVES
•  REVIEW THE CLASSIFICATIONS/NOMENCLATURE OF
DSD
•  OVERVIEW OF NORMAL SEXUAL DIFFERENTIATION
•  REVIEW THE ABNORMAL SEXUAL DIFFERENTIATION
CAUSES
•  EVALUATION AND SURGICAL MANAGEMENT OF
DISORDERS OF SEXUAL DIFFERENTIAION
•  REVIEW SEXUAL ASSINGMENTS AND
PHYSCOLOGICAL IMPLICATIONS
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CASE PRESENATION
CASTER SEMENYA
•  SOUTH AFRICAN 800 M RUNNER
•  WORLD CHAMPION 2009
•  INVESTIGATED AND SUSPENDED FOR PRESUMED ABNORMAL
TESTOSTERONE LEVELS/SUSPICION OF DRUG USE
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CLASSIFICATION OF INTERSEX
•  INTERSEX TERM NO LONGER USED
•  CHANGED TO DISORDER OF SEXUAL
DIFFERENTIOATION
CLASSIFICATION OF DSD
OLD TERMS:
NEW CLASSIFICATION
INTERSEX
DSD
MALE PSEUDO
HERMAPHODITE
46 XY DSD
FEMALE PSEUDO
HERMAPHODITE
46 XX DSD
TRUE HERMAPHODITE
OVOTESTICULAR DSD
XY SEX REVERSAL
46 XY GONADAL
DYSGENESIS
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DSD
WHAT DOES THIS MEAN?
46 XY DSD! UNDERMASCULINIZED MALE
46 XX DSD! OVERMASCULINIZED FEMALE
OVOTESTICULAR DSD! TRUE HERMAPHODITE
MULTI-STEP PATHWAY
CHROMOSOMES DETERMINE GENES
GENES DETERMINE GONADS
GONADS DETERMINE HORMONES
HORMONES NEED RECEPTORS
RECEPTORS NEED ORGANS
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GENETICS
•  SRY DISCOVERED IN 1990
•  FROM TDF LOCUS ON Y CHROMOSOME
•  XX MALES AND XY FEMALES
•  ACTIVATES DOWNSTREAM GENE
EXPRESSION
BIPOTENTIAL FETUS
•  AN AWFUL LOT OF WORK GOES INTO “TRYING” TO
DEVELOP AWAY FROM BEING FEMALE
•  “DEFAULT” BATHED IN ESTROGEN
•  REQUIRES ANDROGEN TO DEVELOP MALE
STRUCTURES
•  REQUIRES MIS TO INHIBIT FEMALE STRUCTURES
•  FUNDAMENTAL ASPECT OF PHYSIOLOGY AND
PATHOPHYSIOLOGY
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GONADS
•  DIFFERENTIATION
STARTS IN 6TH WEEK
•  DEVELOPMENT OF
SERTOLI CELLS
•  MIS FROM SERTOLI AT 7-8
WEEKS
•  PARACRINE
•  ASYMMETRICAL
•  OVARIAN PATHWAY
•  ABSENCE OF MIS
•  POORLY UNDERSTOOD
•  2ND X REQUIRED
•  TURNER’S SYNDROME
INTERNAL GENITALIA
•  WOLFFIAN = MESONEPHRIC
•  MESONEPHRIC FOR KIDNEY
DEVELOPMENT = WOLFFIAN
FOR GENITALS
•  MULTIPLE EMBRYOLOGIC
SEQULAE
•  MÜLLERIAN =
PARAMESONEPHRIC
•  DEVELOPS IN 6TH WEEK
•  LATERAL TO MESONEPHRIC
DUCTS
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ANDROGENS
•  TESTOSTERONE BY 9 WEEKS
•  PEAK AT 13 WEEKS
•  ANDROGEN RECEPTOR
•  VIRILIZATION OF WOLFFIAN DUCT
•  PASSIVE DIFFUSION
•  TISSUE CONVERSION TO DHT
•  INCREASED AFFINITY TO AR
•  UG SINUS, PROSTATE, GENITALIA
•  2 DISTINCT ENZYMES
•  5ΑR 1 : SKIN AND HAIR
•  5ΑR 2: PROSTATE
•  CLONED AND MAPPED TO X CHROMOSOME
External Genitalia
•  GLANS
•  URETHRAL FOLD
•  LABIO-SCROTAL
SWELLING
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EVALUATION OF AMBIGIOUS
GENATALIA
HISTORY
HISTORY IF INFANT DEATH IN FAMILY
HISTORY OF INFERTILITY/AMENORRHEA/
HIRSUTISM
MATERNAL MEDS (STEROIDS/
CONTRACEPTIVES)
PE
PALPABLE GONADS
HYPOSPADIUS (MEATAL POSITION)
STRETCHED PENILE LENGTH
EVALUATION OF AMBIGIOUS
GENATALIA
HYPOSPADIUS AND……
SINGLE PALPABLE UDT- 15%
SINGLE NON PALPABLE UDT-50%
BILATERAL PALPABLE UDT-16%
BILATERAL NON PALPABLE UDT-50%
INCREASED WITH PROXIMAL VS DISTAL HS
65% VS. 5-8%
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EVALUATION OF AMBIGIOUS
GENATALIA
•  INVESTIGATIONS
•  CBC, LYTES, BUN/CR (emergently)
•  T/DHT
•  17 OH PROGESTERONE
•  KARYOTYPE
•  ULTRASOUND
•  GENITOGRAM
•  CYSTOSCOPY
•  MRI
•  LAPAROSCOPY
•  GENITAL BIOPSY
DISORDERS OF SEXUAL
DIFERENTIATION
1) 46 XX DSD
•  CAH
3) DISORDERS OF
GONADAL DIFF
•  MATERNAL ESTROGEN
•  KLINEFELTER,TURNERS
2) 46 XY DSD
•  46 XX MALE
•  DISORDERS OF T
•  PURE/MIXED GONADAL DYS
PRODUCTION
•  DISORDERS OF T
CONVERSION
•  DISORDERS OF ABNORMAL
ANDROGEN RECEPTORS
4) OVOTESTICULAR
DSD
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ABNORMAL DIFFERNTIATION
46 XX DSD (OVERVIRULIZED FEMALE)
1) CONGENITAL ADRENAL HYPERPLASIA
2) MATERNAL EXTROGENS
CONGENITAL ADRENAL
HYPERPLASIA
3 BROAD CATEGORIES
1) SALT WASTING
VIRILIZATION AND SALT WASTING
CLASSIC PRESENTATION AT 10-21 DAYS
WT LOSS, DEHYDRATION, HYPOTENSION,
HYPERKALEMIA
2) SIMPLE VIRILIZATION
MALES PRESENT AT 2-3 YEARS WITH
ISOSEXUAL PRECOCITY
3) NON-CLASSIC
NEITHER SALT WASTING NOR VIRILIZATION
75% SALT WASTING; 25% NON SALT WASTING
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CONGENITAL ADRENAL
HYPERPLASIA
21-HYDROXYLASE DEFICIENCY
•  95% CASES CAH
•  MAJORITY OF AMBIGUOUS GENITALIA
•  1/15,000 US TO 1/490 IN ALASKAN ESKIMOS
•  GENE IS CYP-21
•  10 DIFFERENT MUTATIONS DESCRIBED
•  AR TRANSMISSION
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21-HYDROXYLASE DEFICIENCY
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21-HYDROXYLASE DEFICIENCY
DIAGNOSIS
•  ELEVATED PLASMA PROGESTERONE AND
17-HYDROXYPROGESTERONE
•  IMMUNOASSAY FOR MORE RAPID
DIAGNOSIS
•  URINARY 17 KETOSTEROIDS
•  PELVIC ULTRASOUND
•  MÜLLERIAN STRUCTURES
21-HYDROXYLASE DEFICIENCY
•  HYDROCORTISONE SUPPLEMENTATION
•  SUPPLY DEFICIENCY
•  SUPPRESS ACTH
•  EMPIRICAL DOSE
•  PATIENT, LABS, BP
•  FEMINIZING GENITOPLASTY
•  CONTROVERSIAL
•  CLITOROPLASTY
•  3-12 MONTHS OF AGE
•  LONG TERM FERTILITY FOR WELL MANAGED
•  PROPHYLACTIC ADRENALECTOMY
•  MOST SEVERE CASES; FAILED MEDICAL
MANAGEMENT
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ABNORMAL DIFFERENTIATION
46 XY DSD (UNDERVIRULIZED MALE)
•  ABNORMALITIES OF T PRODUCTION
•  ABNORMALITIES OF T CONVERSION
•  ABNORMALITIES OF T RECEPTORS
46 XY DSD
•  ABNORMALITIES OF T PRODUCTION
•  ENZYMES POSSIBLITIES, ALL VERY RARE
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46 XY DSD
ABNORMALITIES OF T CONVERSION
•  5 ALPHA REDUCTASE DEFICENCY
•  40 DIFFERENT MUTATIONS
•  VARIABLE NEONATAL PHENOTYPE
•  PENOSCROTAL HYPOSPADIUS TO MARKEDLY AMBIGOUS
GENITALIA
•  ABSENCE OF MULLERIAN STRUCTURES
•  UROGENITAL SINUS/LABIOSCROTAL FUSION
•  NORMAL WOLFFIAN STRUCTURES
•  NORMAL VAS AND EPIDIDYMIS
•  T NEEDDED FOR WOLF/DHT NEEDED FOR EXTERNAL GENITALIA
5 ARi
Familial Incomplete Male Pseudohermaphroditism, Type 2 — Decreased
Dihydrotestosterone Formation in Pseudovaginal Perineoscrotal Hypospadias
Patrick C. Walsh, M.D., James D. Madden, M.D., Mary J. Harrod, Ph.D.,
Joseph L. Goldstein, M.D., Paul C. MacDonald, M.D., and Jean D. Wilson,
M.D.
N Engl J Med 1974; 291:944-949
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5AR de/ DHT
5 ARi
Effects of Finasteride
(MK-906), a 5α-Reductase
Inhibitor, on Circulating
Androgens in Male Volunteers
GLENN J. GORMLEY, ELIZABETH
STONER, ROGER S. RITTMASTER, HALL
GREGG, DAVID L. THOMPSON, KENNETH
C. LASSETER, PETER H. VLASSES, and
EVAN A. STEIN
1989
Finasteride started human trials
Decreased levels of DHT
1990
Well tolerated medication
T/DHT ratio returned to normal after stopping
medication
JCEM 1990 70: 1136-1141;
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5 ARi
Decreased prostate size
Increased max flow rates
Effective chronic therapy for Benign Prostatic Hyperplasia
Finasteride vs. Placebo
900 men, daily dose for 12 months
Placebo, 1 mg and 5 mg
Significant decrease in total urinary symptom score
Increase of 1.6 ml/second in max flow rate
19% decrease in Prostatic volume
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46 XY DSD
ANDROGEN RECEPTOR AND POST RECEPTOR
DEFECTS
•  MOST COMMON IDENTIFIABLE CAUSE
•  46 XY WITH TESTES
•  SPECTRUM OF PHENOTYPES
•  SEVERITY OF RECEPTOR DISORDER
•  COMPLETE!”NORMAL” FEMALE
•  PARTIAL ANDROGEN INSENSITVITY
COMPLETE ANDROGEN
INSENSITIVITY
•  46 XY-BILATERAL TESTES
•  FEMALE APPEARING EXTERNAL GENETAILIA
•  ABSENCE OF MULLERIAN STRUCTURES
•  USUALLY DIAGNOSED SECONDARY TO PRIMARY
AMENORRHEA OR TESTES AT INGUINAL
HERNIORRHAPHY
RAISED AS FEMALES
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PARTIAL ANDROGEN INSENSIVITY
•  VARIED AMBIGUITY OF EXTERNAL GENTALIA
•  RANGE FROM HYPOSPADIUS AND A PSEUDOVAGINA
TO GYNECOMASTIA AND AZOOSPERMIA
TWO TYPES OF RECEPTOR DEFECTS
1.  DECREASED NUMBER OR NORMALLY
FUNCTIONING AR
2.  NORMAL RECEPTOR BUT DECREASED BINDING
AFFINITY
MANAGEMENT INDIVIDUALIZED DEPENDING ON
DEGREE OF AMBIGUITY
OVOTESTICULAR DSD
(TRUE HERMAPHODITE)
•  BOTH OVARIAN AND TESTICULAR TISSUE
TESTICULAR TISSUE
Developed seminiferous tubules
OVARIAN TISSUE
Primordial follicles
1 TESTES/1 OVARY, ONE OR TWO OVOTESTES
PHENOTYPE VAIRED
MOST AMBIGOUS, BUT VIRILIZED
75% ARE RAISED AS MALES
60% ARE 46 XX
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OVOTESTICULAR DSD
•  DIFFERENTIATION OF THE INTERNAL DUCTS AS
VARIABLE AS EXTERNAL GENITALIA
•  INTERNAL DUCTS RELATED TO FUNCTION OF
IPSILATERAL GONAD
•  POTENTIAL FOR FERTILITY IF RAISED AS FEMALES
AND APPROPRIATE DUCTAL STRUCTURES
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GONADAL DYSGENESIS
MIXED GONADAL DYSGENESIS
2ND MOST COMMON DIAGNOSIS
MOST HAVE 45 XO/46XY
MAY BE PHENOTYPICALLY
ASYMMETRIC
CONTRALATERAL STREAK GONAD
GONADAL DYSGENESIS
PHENOTYPE VARIABLE
TURNER’S TO AMBIGIOUS TO RARE MALE
PHALLIC ENLARGEMENT, UG SINUS,
LABIOSCROTAL FUSION
UNDESCENDED TESTES (INTRAABDOMINAL)
MULLERIAN STRUCTURES PRESENT
-IPSILATERAL STREAK GONAD
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DSD AND TUMORS
HIGHEST RISK IN COMPLETE DYSGENESIS
-30% TUMOR BY 30 YRS OF AGE
-INCOMPETE DYGENESIS UP TO 15%
-REQUIRE “Y” CHROMOSOME TO BE AT RISK
GERM CELL MALIGNANT DEGENERATION
-SEMINOMA AND NON-SEMINOMA
ALL DYSGENETIC GONADS TO BE REMOVED
-SCROTAL TESTES AT DECREASED RISK
DSD and TUMORS
HIGHEST RISK
Complete gonadal dysgenesis
Partial gonadal dysgenesis with non scrotal gonad
Partial androgen insensitivity and non scrotal gonad
INTERMEDIATE
Partial androgen insensitivity with scrotal gonad
LOW
Complete Androgen Insensitivity
Ovotesticular DSD
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SEXUAL ASSIGNMENT
“John-Joan”Case
•  David (Bruce) Reimer born 1965 (Identical twin)
•  ?phimosis at age 6 months
•  Severe Cautery Injury to penis
Consulted Dr. Money (Hopkins)
•  OR at 22 mo,bilat orchiectomy, urethostomy
•  Raised as a girl (Ideal control w/twin brother)
•  Traumatic visits to Dr.Money
•  Suicidal age 14, parents reviled
•  Age 15 decided to be male (David)
•  Married, stepfather….Suicide age 38
SEXUAL ASSIGNMENT
TWO DIFFERENT SCHOOLS OF THOUGHT
1.  MONEY AND ASSOCIATES
•  PROACTIVE APPROACH, GENDER SPECIFIC ROLE PLAY,
EARLY SURGICAL THERAPY.
•  EXPOSURE TO ANDROGENS IN UTERO/GENETIC SEX
SECONDARY TO SPECIFIC SOCIAL CONTEXT
•  SOCIAL AND CHARACTERISTICS OF EXTERNAL GENITALIA
MOST IMPORTANT FACTORS
(MONEY ET AL. J SEX MARITAL THER 1987)
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SEXUAL ASSIGNMENT
2. DIAMOND AND SIGMUNDSON
•  SEXUAL IDENTITY DOES NOT DEPEND ON
EXTERNAL
GENITALIA
•  GENETIC IMPRINT ON CENTRAL NERVOUS SYSTEM
IN UTERO/EARLY CHILDHOOD
•  POST PUBERTAL HORMONAL CHANGES COINCIDE
WITH IMPRINT
ANDROGEN IMPRINTING OF BRAIN AND INTERSEX DISORDERS
these cells remain alive, but dependent on exposure to testosterone for survival.58
It has also been observed that there are different times
when specific neural and behavioral characteristics are maximally sensitive to steroid hormone influences. For example,
the effect of castration has different time courses on the
luteinizing hormone surge and lordosis behavior in rats.58
Only females and males castrated on postnatal day 1 and not
later showed luteinizing hormone surges after estrogen and
progesterone priming in adulthood. There was a stepwise
decrease in adult lordosis behavior in male rats castrated
postnatally and the response decreased with increasing age
at castration until day 7. These data suggest the existence of
several specific critical periods of different lengths that are
involved in discrete developmental processes of sexual differentiation of the central nervous system, in contrast to a
single critical period for all developmental mechanisms.58
Another important aspect is that hormonal influences on
sexual differentiation of the brain and behavior are seemingly not all or nothing. Each masculine and feminine characteristic exists on a continuum and the amount, duration or
timing of hormone exposure determines its position on the
continuum.35
In humans to our knowledge the exact timing of the critical
period for sexual differentiation of the central nervous system is unknown. However, we can assume that during a
critical period testosterone levels in the circulation are significantly higher in males than in females, similar to the
results of animal experiments. Fetal testis incubation in vitro
and perfusion studies in vivo have shown that testicular
testosterone production occurs as early as 7 to 8 weeks of
gestation.59 By 14 to 18 weeks Leydig cells occupy half of the
volume of the fetal testes, after which they gradually involute
until term.60 Serum testosterone in the male fetus attains a
peak at 14 to 16 weeks.61 At this time values are in the adult
male range, which is essential for male genital differentiation.61 After 24 weeks there is no significant sex difference in
umbilical arterial serum testosterone,62 although the observation that amniotic fluid levels even in late pregnancy are
higher in males than in females61 suggests continued testicular secretion.
While some investigators noted higher testosterone at
term in the umbilical cord and peripheral venous blood samples in males than in females,63 others failed to detect a
significant sex difference.64 In female infants testosterone
concentration remains constantly low during year 1 of life.65
In males the level increases from birth to a peak at 1 to 3
months of life and thereafter it decreases to prepubertal
levels by ages 4 to 6 months (see figure). If we accept that as
2145
in lower animals, testosterone in humans also masculinizes
the central nervous system, we must suppose that these 2
peaks of serum testosterone in males have special significance for sexual development in the male direction.
HYPOTHESIS
Gender identity depends on stepwise exposure to androgen
secretion prenatally, postnatally and at puberty. Although
the exact role of postnatal androgen production is unknown,
we propose that it is a crucial adjunct for masculine development of the brain in animals and humans. Furthermore,
when treating intersex conditions in infants, we should assume that postnatal androgens may masculinize behavior at
least until definitive case-control studies prove otherwise. If
postnatal androgens have a key role as we suspect, infants
with early female gender assignment and suppression or
ablation of androgen production should have better longterm outcome for psychosexual development. Moreover, if
postnatal sexual steroid imprinting occurs, reassigning infants with intersex to the female gender should be avoided
after ages 4 to 6 months.
GENDER ASSIGNMENT
Gender assignment in an individual with intersex is a
serious and sometimes difficult decision with life-long implications. Not only do patients need a gender that they identify
with psychosexually, but also it is equally important to produce functional genitalia consistent with the gender assigned. Money et al first emphasized the role of upbringing in
gender identity development.66 Their studies in the 1950s of
patients with hermaphroditism led to the belief that individuals are psychosexually neutral at birth and become differentiated as male or female during the course of various
growth experiences. They believed that unambiguously raising a child with a physical intersex condition as a member of
the assigned sex would be more important for gender identity
development than chromosomal, gonadal or hormonal sex.67
Money et al recommended early gender assignment with
early corrective surgery in an attempt to identify unambiguously the child with the chosen sex of rearing. The most
important factor for making the decision was “the morphology of the external genitals and the ease with which these
organs can be surgically reconstructed to be consistent with
the assigned sex.”67 The assumption that individuals are
psychosexually undifferentiated at birth was gradually repudiated as further research demonstrated that prenatal hormones can influence certain aspects of human sex dimorphic
behavior in the same direction as in other mammals.
GENETIC IMPRINTING
•  UNKNOWN CRITICAL PERIOD
•  ANDROGENS EXPOSURE ON DEVELOPING BRAIN
MAY BE STRONGEST PREDICTOR
•  TESTOSTERONE SPIKE @ 14-16 WEEKS GESTATION
Mean serum testosterone in male fetus and infant61
HUTSON ET AL. J UROL 2002
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GENETIC IMPRINTING
•  46 XX- CAH, RAISED AS FEMALES
•  MORE “TOMBOYISH” BEHAVOIR/ROUGH PLAY VS. OTHER
GIRLS (Berenbaum, S.A. Psycol Sci 1992, Money et al.
Pschoneuroendocrinology, 1987)
•  HIGHER RATES OF BISEXUAL/HOMOSEXUAL TENDENCIES
(Erhnhardt, A.A. Science 1984)
ANIMAL STUDIES
•  Female rates with exposed to perinatal testosterone reveal male
mating behaviors (Ward,IL. J Physio Psychology 1980)
•  Postnatal testosterone treatment within 1-6 months correlate
strongly with male behaviors (Hrabovszky, Z. J Urol 2002)
SEXUAL ASSIGNMENT
•  WILL ALWAYS BE CONTROVERSIAL
•  PHYSICAL/ PSYCHOSOCIAL ISSUES ARE VAST
•  MULTITEAM APPROACH
•  ENDOCRINOLOGIST
•  PEDIATRIC UROLOGIST
•  PEDIATRIC GYNECOLOGIST
•  PSYCIATRIST
•  GENERAL SURGERY
•  GENDER DYSPHORIA
•  FEELING THAT ONES GENDER IS INCORRECT (DeVries et al.
Pediatric Endo. 1997)
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CASE
CASTOR SEMENYA
•  SUSPENDED BY IAAF UNTIL FURTHER STUDIES
COULD BE PREFORMED
•  IAAF HANDLED CASE VERY POORLY
•  SEMENYA WAS TOLD SHE WAS UNDERGOING
STANDARD DOPING TESTS
•  EXTREME STRESS TO CASTOR AND FAMILY,
INTENSE SCRUTINY AND HUMILIATION
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HYPERANDRODROGENISM
IAAF/IOC
•  WOMEN PRODUCE 1/10TH TESTOSTERONE THAN
MALES
•  “NORMAL” RANGE FOR MALE TESTOSTERONE
>10MMOL/L
•  ONLY FEMALES WHO HAVE TESTOSTERONE LEVELS
BELOW THE “NORMAL” MALE RANGE OR WHO HAVE
AND ANDROGEN RESISTANCE CONDITION ARE
PERMITTED TO PARTICIPATE IN WOMEN’S
COMPETITION
(IAAF 2011)
HYPERANDRODROGENISM
IDENTIFIED ATHLETES MUST UNDERGO:
•  CLINICAL EXAM
•  ENDOCRINE EXAM
•  AND/OR FULL EXAM (GENETIC TESTING, IMAGING,
PSYCHOLOGICAL EVAL)
IF DOES NOT PASS EVALUATION A THERAPEUTIC
PROPOSAL IS ISSUED
•  BANNED FROM COMPETITION UNTIL T IS LOWERED
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SEXUAL ASIGNMENTS
46 XX DSD (CAH/MATERNAL ESTROGENS)
•  FEMALE DIAGNOSIS
•  DIFFERENCE BETWEEN SALT LOSING VS. SIMPLE
VIRILIZING CONDITIONS
ISSUES:
•  ENLARGED CLITORIS
•  LABIAL FUSION
•  UG SINUS/SHORT VAGINA
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GOALS OF SURGERY
•  GENITAL APPEARANCE COMPATIBLE WITH GENDER
•  UNOBSTRUCTED URINARY EMPTYING
•  GOOD ADULT SEXUAL AND REPRODUCTIVE
FUNCTION
RECOMMENDED TIMING FOR SURGERY IS 2-6 MO
AND THEN USUALLY REVISION VAGINOPLASTY IN
ADOLESCENCE
(CONSENSUS STATEMENT ON 21-OH DEF,
CLAYTON ET AL. 2002)
CLITOROPLASTY
•  1930 FIRST REPORTED CASE, WAS AMPUTATION
UNTIL 1970’S
•  DR.PIPPI SALLE-CORPOREAL SPARING
DISMEMBERED TECHNIQUE
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CLITORPLASTY
•  8 PATIENTS
•  FU-6-12 MO
•  ALL CASES RETAINED
DESIRED COSMETIC
APPERANCE
•  ALL GLANS PRESERVED
•  NO EVIDENCE OF PAINFUL
ERECTIONS
PIPPI SALLE ET AL. J UROL 2007
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46 XY DSD- CAIS
•  External female genitalia, bilateral testes, absence of
mullerian structures
100% of patients regarded themselves as female
100% attracted to males in adolescence (93% in adulthood)
78% reported satisfaction with sexual function
46 XY DSD-CAIS
SURGICAL PROCEDURES
•  40% HAD UNDERGONE VAGINOPLASTY
•  AVERAGE AT OF OR 18 YRS OLD
•  NO PTS REQUIRED CLITOROPLASTY
•  RANGE OF LENGTH OF CLITORIS 2-15MM
•  NORMAL XX FEMALE 16+/-4.3 MM
•  100% OF PTS RECEIVED GONADECTOMY PRIOR TO
AGE 21
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46 XY DSD-5 AR deficient
AUTOSOMAL RECESSIVE
NORMAL T=NORMAL SV,VAS,EPIDYMIDES, ED
NO DHT = SEVERE GENITAL AMBIGUITY
CLITORAL-LIKE PHALLUS
BIFID SCROTUM
PSUEDOVAGINA
PS/PERINEAL HS
TESTES-INTRABDO OR W/IN CANAL
46 XY DSD- 5 AR DEFICEINCY
•  ELEVATED LEVELS OF T AT PUBERTY
•  SECONDARY SEXUAL CHARATERISTICS
•  PHALLIC ENLARGEMENT +/- TESTES DECENT
•  “PENIS AT TWELVE”
IF RAISED AS FEMALE, LARGEST REPORTS SHOW
56-63% OF PTS UNDERGO GENDER ROLE CHANGES
FEMALE!MALE AFTER PUBERTY
(COHEN-KETTENIS, P. ACHR SEX BEHAVIOR 2005)
TODAY, ONCE DIAGNOSE KNOW, SUGGESTED ALL TO BE RAISED
AS MALES
(HUGHES ET AL. CONSENSUS STATEMENT 2006)
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NOT SO CLEAR….
•  46 XY DSD- PAIS
•  MIXED GONADAL DYSGENESIS
•  OVOTESTICULAR DSD
•  14 pts with PAIS
•  5/14 living as men, 9/14 as women
•  11 pts with partial gonadal dysgenesis
•  7/11 living as men, 4/11 as women
•  14 pts true hermaphodites
•  9/14 living as men, 5/14 as women
NOT SO CLEAR….
FEMALE DIAGNOSIS
Median 2 OR’s
Low self-reported body image
MALE DIAGNOSIS
Multiple OR’s (0->10)
Low self reported body image
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NOT SO CLEAR….
SEXUAL ASSIGNMENT
SURGICAL MORATORIUM
•  ALL SURGERY (UNLESS MEDICAL EMERGENCY) SHOULD BE
DEALYED UNTIL CHILD ABLE TO MAKE OWN DECISIONS
•  SURGERY IS DAMAGING, MUTILATING, ONLY COSMETIC
(PACIFIC CENTER FOR SEX AND SOCIETY)
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DSD
WILL ALWAYS BE CONTROVERSIAL
MUST CONSIDER
•  PSYCHSOCIAL WELL BEING
•  GENDER IDENTITY
•  SEXUAL APPEARANCE
•  SEXUAL FUNCTION
•  POSSIBILE FERTILITY
•  MINIMIZE NUMBER OF SURGICAL PROCEDURES
CASTER SEMENYA
South African flag bearer at Opening Ceremonies
2012 Olympic Silver medalist
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THANKS TO DR.MACNEILY FOR OVERSEEING
PRESENTAION
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