gynecology 5th year, 3rd lecture (dr. maryam)

There are 3 factors which determine an individual’s sexual development; these are:

1.Effect of sex chromosome on the differentiation of gonads.

2.The proper functioning of the differentiating testis.

3.The response of the end organs to this testicular function.

1.Genetic (chromosomal) sex: the mean by which differentiation is controlled by sex chromosome, 22 autosomes derived from each parent, an embryo that contain 46 chromosomes and has xy will develop as male, but if sex chromosome are xx will develop as female.

2.Gonadal (internal genital) sex: the resulting development of gonad creates either testis or ovary.

3.Phynotypic (external genital) sex: subsequent management of the internal external genitalia gives rise to sex appearance.

The above 3 are collectively called sexual identity or organic sex

4.Brain sex: cerebral differentiation to male or female orientation i.e. sense of maleness/femaleness this is called psychological sex.

So in summary: Weather the fetus is XY or xx is determined

as fertilization. Presence of Y lead to development of testis;

its absence lead to development of ovary. Testis produce Mullerian inhibiting

substance MIS and testosterone. Testosterone lead to development of

Wolffian duct and MIS to Mullerian agenesis; XX lead to Mullerian development.

Dihydrotestosteron cause formation of male external genitalia;XX retain female appearance.

Urogenital sinus

Female external genitalia. Lower part of vagina

Mullerian ducts

Female internal genitalOrgans

. Most of upper vagina

. Cervix and uterus

. Fallopian tubes

Neutral Development

Absence of androgen exposure

Female development

Leydigcells

Sertolicells

Testosterone Mullerian inhibitingfactor

Wollfian duct 5a-reductase

Urogenital sinus

Regrsession of Muuleian ducts

Male external genitalia Male internal Genital organs

DHT

Male development

Cholesterol

Pregnenolone (Pe) 17-OH Pe DHEA 5-Androstenediol

Progesterone (Pr) 17-OH Pr Androstenedione Testosterone

11-DeOxCorticost 11-DeOxCortisol Dihydrotestosterone

Corticosterone Cortisol

18-OH Corticost

Aldosterone

Mineralocorticoids Glucocorticoids Androgens

5-Reductase

3-HSD

21-OH ase

11- OH ase

Or Hermaphroditism is a general term used for a variety of conditions in which a person born with a reproductive or sexual anatomy that does not seem to fit the typical definition of female or male. This is also called ambiguous genitalia.

Incidence: 1:2000 new born mainly (more than

95%) is due to congenital adrenal hyperplasia.

1. Spuedohermaphroditism: a. Musculinization of genetic female (female Spuedohermaphroditism): i.e. genetic XX female with virilized external genitalia e.g. clitorial enlargement or labial fusion; these are due to excess androgen production as in congenital adrenal hyperplasia CAH.

b. Feminization of genetic male (male Spuedohermaphroditism) i.e. genetic XY but with feminized external genitalia, most commonly hypospadius or incomplete fusion of the urogenital fold as in testicular feminization syndrome or enzymatic testicular failure.

 2.True hermaphroditism: i.e. presence of

testicular and ovarian tissue in the same individual and such person commonly genetically female with mosaicism, though genetic male variants also exist.

3.Mixed chromosomal abnormality: in which there is sex chromosome abnormality leading to gonadal dysgenesis interfering with testicular differentiation, the common one is 45X/46XY mosaicism.

could be due to Fetal causes like congenital adrenal

hyperplasia (21 hydroylase deficiency), 11-hydroxylase deficiency, 3 Beta-hydoxysteroid dehydrogenase deficiency.

Most common cause and responsible for> 95% of ambiguous genitalia at birth is 21-hydroxylase deficiency this is an autosomal recessive disorder characterized by salt losing disorder resulting in enzymatic deficiency related to the biosynthesis of cortisol and aldosterone due to failure of conversion of 17 alpha hydroxy progesterone to deoxycortisol the result is high 17 alpha hydroxy progesterone (21 hydroxylase) and high serum deoxycorticosterone, 11-deoxycortisol(11-hydroxylase).

Affected female present with enlargement of clitoris and excessive fusion of genital fold which obsecure the vagina and urethra, thickening and rugosity of the labia majora are evident in similar to scrotum. The uterus, tubes, ovaries are present, vagina opens into urogenital sinus. Salt losing is due to aldosteron deficiency and this may be fatal in first few weeks due to wasting and vomiting.

Maternal causes: maternal ingestion of androgenic drugs during pregnancy like synthetic progesterone, phynetoin, pencillamin, minoxidil.

Like in testicular feminization syndrome(androgen insensitivity) which is a genetic abnormality inherited as Y- linked recessive disorder, secondary sexual characteristic appear at puberty along normal female lines and the disorder is generally not recognized until menarche has failed to occur, this is due to absent androgen receptor. Testes are usually un descended and are located in the inguinal canal or the labial areas

Testicular feminization Testicular feminization syndromesyndrome

46-XY/SRY

TESTIS MIF

Testosterone

External genitalia are generally normal female on examination, with exception of scanty or absent pubic hair; there is short lower 3rd vagina, the gonad has normal testicular histology and serum testosterone are those of normal male but the end organ is not responding.

Because there is MIS substance, the uterus, tubes and upper part of vagina are absent. The breast is present because of peripheral aromatization of testosterone to estrogen.

Other types of XY females are rare like: Swyers syndrome (no SRY or its receptor)

sreak gonad, female external genitalia, female internal genitalia.

5 alpha reductase deficiency 46 XY normal internal male genitalia, female external or ambiguous genitalia.

Leydig cell agenesis partial or complete absence of Leydig cell, no or low testosterone and dihydrotestosterone, ambiguous genitalia with or without male internal genitalia.

Other rare enzyme disorder like 20-22 desmolase, 3,Beta-dehydrogenase ..etc., these are characterized by high testosterone precursor, low DHT, ambiguous genitalia + male internal genitalia.

Both chromosomal sets are present, this condition characterized by dual gonadal development either in the form of ovitest or as a separate ovary and testis. Most true hermaphroditism have some degree of some male and female development internally and externally, the extent to which virilization occur depend on relative amount of testicular tissue. Diagnosis is confirmed at laparoscopy or laparatomy.

TRUE HERMAPHRODITISMTRUE HERMAPHRODITISM

True HP

46XX

May be in the neonatal period with ambiguous genitalia in which the external genitalia is so unusual that is very difficult to identify sex of new born. Also it may present at adolesecence as delayed or heterosexual puberty.

This is a medical emergency; the aim of management is:

1.Saving life of new born as in CAH.2.Accurate diagnosis to avoid immediate

declaration of sex.3.Proper counseling of parents.4.Multidisciplinary approach: obstetrician;

pediatrician; endocrinologist and pediatric surgeon.

By proper history taking; history of any drugs during pregnancy or prior family history. Physical examination; general, abdomen, pelvic, external genital, urethral and anal opening. Then apply Federmans rule who states a palpable organ below inguinal ligament is testis until proven otherwise.

The most important is to exclude CAH so send for:

1.Serum 17 alpha hydroxyl progesterone in blood which will be elevated and urine 17 ketosteroid.

2.Electrolyte level to rule out possibility of salt losing syndrome (sodium and chloride are low and potassium are high).

3.Karyotyping (cord blood or buccal smear).4.Ultrasound, MRI to check uterus and vagina.5.Some time biopsy of skin to check 5-alpha

reductase activity.6.Laparatomy or laparoscopy for gonadal biopsy

and removal.

Immediate management of such child should always be undertaken by or incorporation with pediatrician to replace necessary cortisol or one of its related synthetic compound to suppress adrenocorticotrophic hormone secretion and if the baby is salt losing this should be very carefully corrected.

Further aspect of management may be required:

1.Sex assignment for children, this should be done completing investigation usually by age of 18 and this is done according to degree of ambiguity e.g. presence of phallus > 2 cm and erectile tissue should be assigned as male, while short phallus can be assigned as female.

2.Gonadal malignancy risk: removal of any intra abdominal gonad and streak gonad in Y chromosome carrier.

3.Surgical correction: like clitorial reduction, vaginal repair and construction e.g. dilatation or McIndoe vaginoplasty.

4.Psychological and genetic counseling of other family member.

The person strongly believes in belonging to opposite sex; treatment is by psychiatric.

Thanks and Happy valentine