Sexuality and sexual development disorders Flashcards
Anomalies of Mullerian Duct Fusion
- Mullarian agenesis
- unicornuate uterus
- didelphic uterus
- bicornate uterus
- septate uterus
- DES- related abnormality
Anomalies of mullerian duct fusion
Pathophysiology
- Defective fusion of the Müllerian ducts during embryonal development
- Normally functioning gonads and female karyotype → normal development of secondary sexual characteristics(e.g., breast, pubic hair development)
Abnormalities of Mullerian Duct Fusion
Clinical Features
- Asymptomatic before puberty
- Infertility and dyspareunia
- In some cases, periodic lower abdominal pain
- Menorrhagia (bicornate)
- Müllerian agenesis: primary amenorrhea
Anomalies of Mullerian duct fussion
obstetric complications
increased risk of the following:
- Ectopic pregnancy
- Cervical incompetence
- Preterm labor
anomalies of mullerian duct fusion
diagnostics
- Screening tests
- Transvaginal or abdominal ultrasound
- Hysterosalpingography
- Confirmatory test:
- MRI
Hysterosalpingography
radiologic procedure in which contrast dye is injected into the cervical canal and serial x-rays are obtained in order to evaluate the uterine cavity and fallopian tubes.
anomalies of mullerian duct fussion
Tx
Metroplasty- reconstruction of uterus.
Rull out other causes of infertility before surgery
Mullerian Agenesis
Both the Müllerian ducts fail to develop → absent or hypoplastic uterus, absent cervix, and vaginal atresia
Unicornate Uterus
one of the mullerian ducts fails to develop
Bicornate uterus
incomplete fussion of the mullerian ducts to various degrees
- unicollis: double uterus, single cervix, and single vagina
- bicollis: double uterus and double cervix with/without a vaginal septum
Didelphic Uterus
Complete lack of Mullerian duct fusion
Double uterus, double cervix, double vagina
Septate Uterus
The Müllerian ducts fuse, but the septa between the two ducts persists either partially (subseptate uterus) or completely (septate uterus).
DES related abnormality
In-utero exposure to diethylstilbestrol
- Vagina: adenosis, adenocarcinoma
- Cervix: cockscomb cervix, cervical collar
- Uterus: hypoplasia, uterine synechiae, T-shaped uterine cavity
- Fallopian tube: abnormal fimbriae, cornual budding
Imperforate Hymen
a hymen without an opening
etiology: congenital
imperforated hymen
pathophys
- the urogenital sinus do not disintegrate →
- imperforate hymen →
- cryptomenorrhea at puberty(outflow tract obstruction leads to backup of menstrual blood) →
- hematocolpos
imperforated hymen
clinical features
- Asymptomatic before puberty
- Primary amenorrhea with periodic lower abdominal pain
- Possible palpable lower abdominal mass
- Perineal examination: tense, bulging, bluish membrane in the vulva
imperforated hymen
Tx
hymenectomy
Vaginal atresia
Absent or malformed uterus and cervix
- Agenesis or hypoplasia of the Müllerian duct → atresia of the upper ⅓ of the vagina
- Normally functioning gonads and female karyotype → normal development of secondary sexual characteristics
Vaginal Atresia
Clinical Features
- Asymptomatic before puberty
- Primary amenorrhea
- Infertility
- Dyspareunia
- Perineal examination: vaginal dimple and a hymenal fringe
Vaginal Atresia
Diagnostics
- Normal levels of LH, FSH, prolactin, estradiol, and testosterone
- Confirmatory test: ultrasound
- Limited view of the uterus und vagina
- associated malformations of the kidneys or urinary tract
Vaginal Atresia
Tx
vaginoplasty
Transverse Vaginal Septum
- Failure of recanalization of the Müllerian duct → transverse septum
- Cryptomenorrhea → hematocolpos
Transverse Vaginal Septum
Clinical Features
- Asymptomatic before puberty
- Primary amenorrhea
- Infertility
- Possibly, palpable lower abdominal mass
- Perineal examination: normal vulva and external genitalia
Transverse Vaginal Septum
Treatment
- First-line: nonsurgical dilation over 6–12 months using graduated vaginal dilators
- Second-line: vaginoplasty
Labial Fusion
Partial or complete adhesionof the labia minora
Labial Fusion
Etiology
- Absence of estrogen →
- predisposition to mild infection →
- local inflammation →
- raw surface epithelium of the labia minora →
- adhesions
Labial Fusion
Clinical Features
- If external urethral opening is obstructed: recurrent attacks of UTI, vaginitis, vestibulitis
- Perineal examination
- A thin vertical midline fold in the perineum
- The labia, vaginal opening, and occasionally the urethral meatus are not visible
Labial Fusion
Tx
Topical estrogen
Androgen Insensitivity SYndrome
disorder of sexual development caused by an X-linked recessive loss of function mutation in the gene encoding the androgen receptor. Patients are karyotypically male (XY)
Androgen insensitivity Syndrome
Clinical Features
Complete androgen insensitivity
- Female external genitalia and physique
- Blind-ended vaginal pouch, uterine agenesis (due to anti-Mullerian hormone secretion)
- Absent male internal genitalia (with the exception of the testes)
- Cryptorchid testes: intra-labial, inguinal or abdominal localization of undescended testicles
- Scant or no pubic hair
- Primary amenorrhea, infertility (no menarche)
ANdrogen insensitivity syndrome
diagnosis
- Before puberty: ↑ testosterone
- After puberty: ↑ LH, ↑ estrogen, and normal/↑ testosterone levels (no virilization)
- Genetic testing
androgen insensitivity syndrome
Tx
depends on receptor status as well as on the patient’s phenotype and gender identity
- Hormone treatment
- Complete androgen insensitivity: estrogen replacement
- Partial androgen insensitivity: high-dose androgen therapy can be used in patients with male gender identity
- Gonadectomy for intra-abdominal/intra-labial testicles
- Typically performed after puberty
- Prevents malignant transformation of the abnormally localized gonads
Aromatase Deficiency
Mutations in the CYP19A1 gene which encodes for the enzyme aromatase → ↓ serum estrogenand ↑ serum testosterone
both XX and XY
aromatase deficiency
Clinical Features
XY- normal sex development
XX:
- Birth: Ambiguous genitalia despite normal internal genital organs
- Puberty
- Impaired maturation of secondary sexual characteristics
- Primary amenorrhea
- Virilization (e.g., hirsutism, severe acne)
Both:
- Tall stature
- osteoporosis
Mother- virilization during pregnancy
aromatase deficiency
Tx
- Estrogen and progesterone replacement therapy
- Calcium and vitamin D supplementation
- Surgical correction of ambiguous genitalia
5 Alpha reductase deficiency
- Normal testosterone production
- Defective 5-alpha-reductase: testosterone not converted into dihydrotestosterone (DHT) → DHT-dependent virilization of genitalia does not occur
- Etiology: rare autosomal recessive loss-of-function mutation of chromosome 2
- Karyotype: 46,XY
5 alpha reductase deficiency
Clinical features
- Female external genitalia at birth,
- Internal urogenital organs are male
- In puberty, increasing synthesis of testosterone leads to virilization (phallic growth, testicular descent, development of male gender identity)
5 alpha reductase deficiency
diagnostics
- n/↑ testosterone, ↓ DHT, increased ratio
- Genetic testing for definitive diagnosis
5 alpha reductase deficiency
tx
- Female gender identity: gonadectomy; estrogen substitution therapy upon completion of longitudinal growth
- Male gender identity: testosterone substitution
Klinefelter SYndrome
47XXY
nondisjucntion of sex chormosomes during meiosis.
associated with advanced maternal age
kleinfelter syndrome
clinical features
- Male phenotype
- Testicular dysgenesis and subsequent testosterone deficiency:
- Eunuchoid growth pattern; tall, slim stature with long extremities
- Gynecomastia, reduced body hair
- Testicular hypoplasia with a normal sized penis
- Reduced fertility
Associations:
- Mitral valve prolapse
Klinfelter syndrome
diagnosis and tx
- Diagnostics: karyotyping confirms the diagnosis
- Therapy: testosterone substitution
Turner Syndrome
Nondisjunction during meiosis → complete sex chromosomal monosomy → 45 XO, no Barr body
of Mosaiacism (with bar boddy)
turner syndrom clinical features
- Female phenotype
- Lymphedema in the neonatal period affecting the hands and feet (due to abnormal development of the lymphatic system)
- Short stature, shield chest, widely spaced nipples, cubitus valgus;
- High arched palate,
- Webbed neck: skin folds along the side of the neck between the mastoid process and the acromion
- Hypertension (even in children)
- Gonadal dysgenesis with streak gonads :
- Delayed puberty
- Primary amenorrhea
- Infertility
Turner syndrom associated issues
- Cardiovascular abnormalities
- Bicuspid aortic valve
- Coarctation of the aorta
- Aortic dissection and rupture
- Kidney and ureter malformations;
- especially horseshoe kidney
- Osteoporosis and pathologic fractures
Turner Syndrome
Diagnosis
- Hypergonadotropic hypogonadism → ↓ estrogen, ↓ androgens, ↑ follicle stimulating hormone, ↑ luteinizing hormone
- Karyotyping
Turner Syndrome
Tx
estrogen and progestogen substitution
Kallmann Syndrome
a form of hypogonadotropic hypogonadism, associated with hyposmia/anosmia
isolated GnRH deficiency in conjunction with anosmia.
males>females
Anosmia/ hyposmia
loss of sense of smell complete and partial respectively
Kallmann SYndrome clinical Features
- Anosmia or hyposmia
- Infertility
- male: cryptorchidism and low sperm count
- female: primary amenorrhea
- Absent or attenuated pubertal changes
Associated disorders
- Renal agenesis
- Cleft lip/palate
Kallmann Syndrome
Tx
Hormone replacement therapy is given in puberty to stimulate the development of secondary sexual characteristics.
- For men: testosterone
- For women: estrogen and progesterone combination therapy
Gonadotropins or pulsatile GnRH therapy is used to increase fertility
