Puberty

1
Puberty

• Clinic of Reproduction and Gynecology
• Pomeranian Medical Academy
• Iwona Szydlowska

2

• It is a physiological phase lasting 2 to 5
  years, during which the genital organs mature

3
SEXUAL MATURATION

• Physical, emotional and sexual transition from
  childhood to adulthood
• Gradually. Sequence of physiological changes.

4

• The first sign of pubertal development is usually
  breast growth (thelarche), followed by appearance
  of pubic hair (pubarche), then axillary hair
  (adrenarche), then menarche.
• The mean interval between breast budding and
  menarche is 2.5 years with a standard deviation
  of about one year.

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ADRENARCHE

• Somatic changes dependent on adrenal steroid
  hormones
• means increased activity of the suprarenal cortex
  at puberty with increased production of adrenal
  androgens which lead to appearance of pubic and
  axillary hair.

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GONADARCHE

• Somatic changes dependent on gonadal sex steroid
  hormones

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CAUSE OF PUBERTY

• During childhood, the hypothalamus is extremely
  sensitive to the negative feedback exerted by the
  small quantities of estradiol testosterone
  produced by the child's ovaries.
• As puberty approaches, the sensitivity of the
  hypothalamus is decreased and subsequently, it
  increase the pulsatile GnRH secretion .

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CNS-Hypothalamus-Pituitary Ovary-Uterus
Interaction
Neural control
Chemical control
Dopamine (-)
Norepinephrine ()
Endorphines (-)
Hypothalamus
Gn-RH
?


Ant. pituitary
FSH, LH
Ovaries
Progesterone
Estrogen
Uterus
Menses
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HYPOTHALAMUS-PITUITARYOVARIAN AXIS

• Necessary for the normal sexual maturation.
• Pulsatile secretion of gonadotropins begins the
  maturation process.
• Important is not the amplitude of Gn pulses, but
  the frequency.
• In the late prepubertal period secretion of Gn is
  reinforced subsequent pulses of GnRH reinforce
  the release of Gn.
• Activation of positive and negative feedback
  loops at puberty.

10

• The anterior pituitary responds by progressive
  secretion of FSH and LH associated with increased
  secretion of growth hormone.

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• The ovaries respond to the increase Gonadotrophin
  secretion by follicular development estrogen
  secretion.

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• Estrogen causes development of the genital organs
  and the appearance of the secondary sexual
  characters.
• With increased estrogen secretion, menarche and
  cyclic estrogen secretion occurs.

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SECONDARY SEX CHARACTERS INCLUDE

• development of the breast,
• appearance of pubic and axillary hair.

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FACTORS AFFECTING THE INITIATION OF PUBERTAL
DEVELOPMENT

• 1 - Height and weight ratio- 48 kg (nutritional
  factors).
• 2 - Maturation of the hypothalamus.
• 3 - Increased neurotransmitter output in CNS.
• 4 - Onset of adrenal androgen activity.

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DEPOSITION OF SC FAT

• 17 to menstruate
• 22 to ovulate

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PUBERTY

• Five stages from childhood to full maturity (P1
  to P5), described by Marshall and Tanner. In both
  sexes, these stages reflect the progressive
  modifications of the external genitalia and of
  sexual hair. Secondary sex characteristics appear
  at a mean age of 10.5 y in girls and 11.5 to 12 y
  in boys.

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SEQUENCE AND AGE OF SEXUAL MATURATION AND
HORMONES RESPONSIBLE FOR THIS PROCESSES.
Event Age (mean) Hormones
Thelarche (breast budding) Pubarche (sexual hair growth) Growth spurt Menarche Adult breast development Adult sexual hair 10,5 10,6 12,0 12,7 13,7 14,7 Estradiol Androgens GH Estradiol Progesterone Androgens
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FEMALE PUBERTAL STAGES (TANNER)

• P1 Prepubertal
• P2 Early development of subareolar breast bud
  /- small amounts of pubic hair and axillairy
  hair
• P3 Increase in size of palpable breast tissue
  and areolae, increased amount of dark pubic
  hair and/of axillary hair
• P4 Further increase in breast size and areolae
  that protrude above breast level adult pubic
  hair
• P5 Adult stage, pubic hair with extension to
  upper thigh

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TANNERS CLASSIFICATION OF SEXUAL MATURITY
BREASTS

• Th 1- child (only papillae are elevated)
• Th 2 prepubertal (breast bud and papilla are
  elevated and a small mount is present areola
  diameter is enlarged) age 11,2 yrs (9,0-13,3
  yrs)
• Th 3 - early pubescent, age 12,2 yrs (10,0-14,3)
• Th 4 - late pubescent, age 13,1 yrs (10,8-15,3)
• Th 5 - adult mature breast (recession of areola
  to the mound of breast tissue, rounding of the
  breast mound, and projection of only the papilla
  are evident) age 15,3 yrs (11,9-18,8)

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TANNERS CLASSIFICATION OF SEXUAL MATURITY PUBIC
HAIR

• P1- prepubertal/Pre-adolescent (vellus hair only,
  no pubic hair)
• P2 - presexual hair (sparse growth of long,
  slightly pigmented, downy hair or only slightly
  curled hair, appearing along labia) - age 11,7
  (9,3-14,1)
• P3 - sexual hair (hair is darker, coarser, more
  curled, and spreads above the syphysis pubis)
  age 12,4 (10,2-14,6)
• P4 - mild-escutcheon (Adult-type hair area
  covered is less than that in most adults there
  is no spread to the medial surface of thigh)
  age 13,0 (10,8-15,1)
• P5 - female escutcheon (Adult-type hair with
  increased spread to medial surface of thighs
  distribution is as an inverse triangle) age
  13,4 ( 12,2-16,7)

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GENITAL ORGANS CHANGES

• Mons pubes, labia majora minora
  increase in size.
• Vagina
• length increase, appearance of the rugae
• epithelium thick, stratified squamous,
  containing glycogen
• pH acidic.

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GENITAL ORGANS CHANGES

• Uterus
• enlarge, Uterus / Cervix 2 / 1
• Ovaries
• Increase in size, almond shape
• 300 thousands primary follicle at menarche (2
  million at birth)

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• In prepuberty, the ovarian size volume extends
  from 0.3 to 0.9 cm3. More than 1.0 cm3 indicates
  that puberty has begun. During puberty, the
  ovarian size increases rapidly to a mean
  postpubertal volume of 4.0 cm3 (1.8 to 5.3 cm3).

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MENARCHE

• During puberty, plasma E2 levels fluctuate
  widely, probably reflecting successive waves of
  follicular development that fail to reach the
  ovulatory stage. The uterine endometrium is
  affected by these changes and undergoes cycles of
  proliferation and regression, until a point is
  reached when substantial growth occurs so that
  withdrawal of estrogen results in the first
  menstruation (menarche).

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OVULATION

• Plasma progesterone remains at low levels even
  if secondary sexual characteristics have
  appeared. A rise in progesterone after menarche
  is, in general, indicative that ovulation has
  occured. The first ovulation does not take place
  until 6-9 months after menarche because the
  positive feedback mechanism of estrogen is not
  developed.

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ADOLESCENCE

• Is the period of life during which the child
  becomes an adult person
• i.e. the physical , sexual and psychological
  development are complete .
• Puberty represents the first part of adolescence .

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ABNORMALITIES OF PUBERTY

• 1 - Precocious puberty.
• 2 - Delayed puberty.
• 3 - Growth problems
• during adolescence e.g. short stature or tall
  stature, marked obesity and menstrual disorders
  at puberty .

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• FEMALE PRECOCIOUS PUBERTY

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DEFINITION

• It means menarche or appearance of any of the
  secondary sexual characters before the age of 8
  years.

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TYPES

• 1 - True precocious puberty.
• 2 - False (pseudo-precocious puberty).
• 3 - Incomplete precocious puberty.

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1. TRUE (CENTRAL,CEREBRAL) PRECOCIOUS PUBERTY.

• It is due to increased production of pituitary
  gonadotrophins.

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2. FALSE (PERIPHERAL) PRECOCIOUS PUBERTY

• It is of peripheral origin.
• It is due to secretion of sex hormones (estrogen
  or androgen) which is not dependent on pituitary
  gonadotrophins as in case of estrogenic or
  androgenic ovarian tumors.

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2. FALSE (PERIPHERAL) PRECOCIOUS PUBERTY

• False precocious puberty may be isosexual or
  heterosexual.
• A girl who feminizes early is defined as having
  isosexual precocious puberty.
• A girl who virilize early is defined as having
  heterosexual precocious puberty. (female
  pseudohermaphrodite)

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3. INCOMPLETE PRECOCIOUS PUBERTY

• In this case only one pubertal change as breast
  development is present before the age of 8 years
  without the presence of any other pubertal
  changes and in absence of increased estrogen
  production.
• The other pubertal changes occur at the normal
  age.

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3. INCOMPLETE PRECOCIOUS PUBERTY

• Incomplete forms of precocious puberty include
  premature thelarche (unilateral or bilateral),
  premature pubarche and premature adrenarche with
  appearance of pubic and axillary hair.

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PRECOCIOUS PUBERTY - TERMS

• breast development - premature thelarche,
• pubic development - premature pubarche
• axillary hair development - premature adrenarche
• menses - premature menarche

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ETIOLOGY OF PRECOCIOUS PUBERTY

• 1.Constitutional or idiopathic
• In most cases of precocious puberty (90) no
  cause is found.
• For some unknown reason the hypothalamus
  stimulates the pituitary gland to secrete its
  gonadotrophic hormones.
• There is normal menstruation and ovulation.
• Pregnancy can occur at young age.

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ETIOLOGY OF PRECOCIOUS PUBERTY

• 2. Organic lesions of the brain
• The next common cause.
• Organic lesions affecting the midbrain,
  hypothalamus, pineal body, or pituitary gland may
  lead to premature release of pituitary
  gonadotrophins.
• Examples include traumatic brain injury,
  meningitis, encephalitis, brain abscess, brain
  tumor as glioma, craniopharyngioma, and
  hamartomas.
• 3. McCune-Albright syndrome.

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McCune-Albright Syndrome

• The disease is found more frequently in girls.
• It consists of a triad of
• Precocious puberty,
• Cystic changes in bones, and
• Cafe-au lait patches of the skin.
• The cause of precocious puberty is autonomous
  production of estrogen by the ovaries.
• FSH and LH levels are low.
• The treatment is testolactone oral tablets which
  inhibit ovarian steroidogenesis.

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ETIOLOGY OF PRECOCIOUS PUBERTY

• 4. Adrenal causes
• (a) Hyperplasia, adenoma, or carcinoma of
  suprarenal cortex.
• Congenital adrenal hyperplasia and Cushing
  syndrome lead to precocious puberty in the male
  direction, i.e. heterosexual precocious puberty
• (b) Estrogen secreting adrenal tumor which is
  very rare.

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ETIOLOGY OF PRECOCIOUS PUBERTY

• 5. Ovarian causes
• (a) Estrogen producing tumors as granulosa and
  theca cell tumor
• (b) Androgen producing tumors as androblastoma
• (c) Choriocarcinoma because it secretes human
  chorionic gonadotrophin (HCG) which may stimulate
  the ovaries to secrete estrogen
• (d) Dysgerminoma if it secretes HCG.

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ETIOLOGY OF PRECOCIOUS PUBERTY

• 6. Juvenile hypothyroidism
• Lack of thyroxine leads to increased production
  of TSH and the secretion of pituitary
  gonadotrophins may also be increased.
• 7. Drugs
• Iatrogenic may follow oral or local
  administration of estrogen.
• A long course of estrogen cream used for
  treatment of vulvovaginitis of children may lead
  to breast development or withdrawal bleeding.

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DIAGNOSIS OF PRECOCIOUS PUBERTY

• 1. History
• It excludes iatrogenic source of estrogen or
  androgen.
• It differentiates between isosexual and
  heterosexual precocious puberty.

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DIAGNOSIS OF PRECOCIOUS PUBERTY

• 2. Physical examination
• It diagnoses McCune-Albright syndrome.
• Neurologic and ophthalmologic examinations
  exclude organic lesions of the brain.

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DIAGNOSIS OF PRECOCIOUS PUBERTY

• 3. Special investigations
• These are done according to the history and
  clinical findings and include

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3. SPECIAL INVESTIGATIONS

• a. X-ray examination of the hand and wrist
  to determine bone age.
• Estrogen stimulates growth of bone but causes
  early fusion of the epiphysis.
• So the child is taller than her peers during
  childhood, but she is short during adult life.

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3. SPECIAL INVESTIGATIONS

• b. Hormonal assay
• including serum FSH, LH, prolactin, estradiol,
  testosterone, 17a-hydroxy progesterone, TSH, and
  human chorionic gonadotrophin to diagnose
  Choriocarcinoma.

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3. SPECIAL INVESTIGATIONS

• c. Ultrasonography
• to diagnose ovarian or adrenal tumor.
• d. CT or MRI
• to diagnose an organic lesion of the brain, or
  adrenal tumor.

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• Hypothyroidism retards bone age and is the only
  condition of precocious puberty in which bone age
  is retarded

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IDIOPATHIC PRECOCIOUS PUBERTY

• is diagnosed after excluding all other causes.

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TREATMENT OF PRECOCIOUS PUBERTY

• Objectives
• Arrest maturation until normal pubertal age.
• Attenuate diminish established precocious
  characteristics.
• Maximize adult height.
• Avoid abuse, reduce emotional social problems

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TREATMENT OF PRECOCIOUS PUBERTY

1. Treatment of the cause, e.g., thyroxin for
   hypothyroidism, removal of ovarian and adrenal
   tumors.
2. Incomplete forms of precocious puberty do not
   require treatment, as estrogen production is not
   increased.

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McCune-Albright syndrome

• Is treated with testolactone oral tablets.
• The drug inhibits the formation of estrogen from
  its precursors, so reduces estrogen level.
• The dose is 20 mg/kg body weight in 4 divided
  doses and increased to 40 mg/kg body weight
  during a 3 week interval.

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IDIOPATHIC TYPE

• is treated by explanation and reassurance and by
  giving one of the following drugs which inhibit
  the secretion of gonadotrophins
• (a) Gonadotrophin releasing hormone analogues
  which are given as daily nasal spray,
  intramuscular, or subcutaneous injections every 4
  weeks.
• (b) Medroxyprogesterone acetate tablets (Provera
  tablets) or intramuscular injection
  (Depo-Provera)
• (c) Danazol capsules
• (d) Cyproterone acetate tablets (Androcur).

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IDIOPATHIC TYPE

• Treatment is given till the age of 12 years (mean
  age of pubertal development).

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Gonadotrophin releasing hormone analogues

• Drug of choice because it achieves all
  objectives
• It acts by binding to the anterior pituitary
  receptors causing down-regulation
  desensitization of the pituitary.
• Regression of symptoms occurs in the first year
• Delayed epiphyseal fusion treatment more
  effective if begun before bone age gt12 yrs.
• Maintain E2 at lt10 pg/mL.
• Children require higher doses than adults for
  suppression.
• Adrenarche will continue.

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DELAYED PUBERTY

• Secondary Sexual Characters do not develop
  by the age of
• 14 yrs
• or
• no menstruation till age of 16yrs

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DELAYED PUBERTY

• It is either
• Delayed onset Breast bud does not appear till 13
  years or menarche does not occur till 16 years.
  
• or
• Delayed progreession Menarche does not occur
  within 5 years after breast bud.

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ETIOLOGY OF DELAYED PUBERTY

• 1 - Constitutional
  with ve family history,
  short stature normal fertility.
• 2 - Hypergonadotropic hypogonadism (FSH gt 40)
  ovarian causes of Iry amenorrhea primary
  ovarian failure 2ry ovarian failure (if occurs
  before puberty).
• 3 - Hypogonadtropic hypogonadism hypothalamic
  pituitary causes of Iry amenorrhea e.g. Kallman's
  syndrome, Anorexia nervosa.

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ETIOLOGY OF DELAYED PUBERTY

• 4 - Normogonadtropic hypogonadism end organ
  defects uterine causes (Mullerian agenesis and
  testicular feminization syndrome), imperforate
  hymen (c/o delayed menarche normal other
  aspects of puberty), PCOD and Virilizing ovarian
  adrenal tumors.
• 5 - General causes of amenorrhea (endocrinal or
  non-endocrinal especially malnutrition) if
  occurred before puberty ?GH steroid synthesis
  defects .

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INVESTIGATIONS OF DELAYED PUBERTY

• History
• 1 - Family history, nutritional history, any
  systemic diseases (e.g. history of endocrinal
  disturbances).
• 2 - Clinical picture of space occupying lesion in
  the ovary, adrenal, pituitary hypothalamus.
• 3 - Periodic pain and ve 2ry sexual
  characteristics in imperforate hymen .

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INVESTIGATIONS OF DELAYED PUBERTY

• Examination
• (A) Body measurement for causes of amenorrhea ?
  or ? weight, short or tall stature, proportions
  (upper/lower segment ratio arm span/height
  ratio).
• (B) Tanner staging of breast, pubic axillary
  hair if present.
• (C) Clinical picture of Turner, Mullerian
  agenesis imperforate hymen.
• (D) Neurological examination for smell sense
  (Kallman's syndrome), visual field other
  cranial nerve lesions .

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SPECIAL INVESTIGATIONS

• 1 - FSH LH assay important to differentiate
  level of the lesion progesterone assay in 17 OH
  deficiency.
• 2 - Chromosomal study if short stature or
  hypergonadotropic type.
• 3 - Radiological bone age study radiologic
  study for pituitary adenoma.

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AMENORRHEA
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DEFINITIONS

• Primary amenorrhea
• Failure of menarche to occur when expected in
  relation to the onset of pubertal development.
• ? No menarche by age 16 years with signs of
  pubertal development.
• ? No onset of pubertal development by age 14
  years.

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PATHOPHYSIOLOGY OF AMENORRHEA

• Inadequate hormonal stimulation of the endomerium
  Anovulatory amenorrhea
• - Euestrogenic
• - Hypoestrogenic
• Inability of endometrium to respond to hormones
  Ovulatory amenorrhea
• - Uterine absence - Utero-vaginal agenesis
• - XY-Females
  (e.g T.F.S)
• - Damaged endometrium (e.g Ashermans
  syndrome)

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EUESTROGENIC ANOVULATORYAMENORRHEA

• Normal androgens
• Hypothalamic-pituitary dysfunction (stress,
  weight loss or gain, exercise)
• Hyperprolactinemia
• Feminizing ovarian tumour
• Non-gonadal endocrine disease (thyroid, adrenal)
• Systemic illness

• High androgens
• PCOS
• Musculinizing ovarian tumour
• Cushings syndrome
• Congenital adrenal hyperplasia (late onset)

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HYPOESTROGENIC ANOVULATORYAMENORRHEA

• Normal androgens
• - Hypothalamic-pituitary failure
• - Severe dysfunction
• - Neoplastic,destructive,
• infiltrative, infectious
• trumatic conditions
• involving hypothalamus or pituitary
• - Ovarian failure
• - Gonadal dysgenesis
• - Premature ovarian failure
• - Enzyme defect
• - Resistant ovaries
• - Radiotherapy, chemotherapy

• High androgens
• - Musculinizing ovarian tumour
• - Cushings syndrome
• - Congenital adrenal hyperplasia (late onset)

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DIAGNOSIS

• HISTORY
• PHYSICAL EXAMINATION
• ULTRASOUND EXAMINATION

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CRYPTOMENORRHEA

• Outflow obstruction to menstrual blood
• Imperforate hymen
• Transverse Vaginal septum with functioning uterus
• Isolated Vaginal agenesis with functioning uterus
• Isolated Cervical agenesis with functioning
  uterus
• Intermittent abdominal pain
• Possible difficulty with micturition
• Possible lower abdominal swelling

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IMPERFORATE HYMEN
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Once cryptomenorrhea are excluded The patient is
a bioassay for Endocrine abnormalities
Four categories of patients are identified
1. Amenorrhea with absent or poor secondary sex
characters
2. Amenorrhea with normal 2ry sex characters
3. Amenorrhea with signs of androgen excess
4. Amenorrhea with absent uterus and vagina
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AMENORRHEAAbsent or poor secondary sex
Characteristics
FSH Serum level
Low / normal
High
Hypogonadotropic hypogonadim
Gonadal dysgenesis
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AMENORRHEANormal secondary sex Characteristics

• - FSH, LH, Prolactin, TSH
• Provera 10 mg PO daily
• x 5 days

Bleeding
No bleeing
?Prolactin ? TSH
- Mild hypothalamic dysfunction - PCO
(?LH/FSH)
Further Work-up (Endocrinologist)
Review FSH result And history (next slide)
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FSH
Low / normal
High
Hypothalamic-pituitary Failure
Ovarian failure
head CT- scan or MRI
?If lt 25 yrs or primary amenorrhea ? karyoptype
?If lt 35 yrs ?autoimmune disease
- Severe hypothalamic dysfunction - Intracranial
pathology
?? Ovarian biopsy
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AMENORRHEA Utero-vaginal absence
Karyotype
46-XX
46-XY
Mullerian Agenesis (MRKH syndrome)
Andogen Insenitivity (TFS syndrome)
. Gonadal regression . Testicular enzymes
deficiency . Leydig cell agenisis
Normal breasts absent sexual hair
Normal breasts sexual hair
Absent breasts sexual hair
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AMENORRHEA Signs of androgen excess
Testosterone, DHEAS, FSH, and LH
DHEAS gt700 mug/dL
DHEAS 500-700 mug/dL
TEST. gt200 ng/dL
?Serum 17-OH Progesterone level
U/S ? MRI or CT
Ovarian Or adrenal tumor
Adrenal hyperfunction
Late CAH
Lower elevations ? PCOS (High LH / FSH)
78
AMENORRHEA

• PRIMARY AMENORRHEA
• Ovarian failure 36
• Hypogonadotrophic hypogonadism 34
• PCOS 17
• Congenital lesions (other than dysgenesis)
  4
• Hypopituitarism 3
• Hyperprolactinaemia 3
• Weight related 3

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GONADAL DYSGENESIS

• Chromosomally incompetent
• - Classic Turners syndrome (45XO)
• - Turner variants (45XO/46XX),
• (46X-abnormal X)
• - Mixed gonadal dygenesis (45XO/46XY)
• Chromosomally competent
• - 46XX (pure gonadal dysgenesis)
• - 46XY (Swyers syndrome)

80
TURNERS SYNDROME

• Sexual infantilism and short stature.
• Associated abnormalities, webbed neck,
  coarctation of the aorta, high-arched pallate,
  cubitus valgus, broad shield-like chest with
  wildely spaced nipples, low hairline on the neck,
  short metacarpal bones and renal anomalies.
• High FSH and LH levels.
• Bilateral streaked gonads.
• Karyotype - 80 45, X0
• - 20 mosaic forms
  (46XX/45X0)
• Treatment HRT

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TURNERS SYNDROME
Mosaic (46-XX / 45-XO)
(Classic 45-XO)
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OVARIAN DYSGENESIS
83
NONE-DYSGENESIS OVARIAN FAILURE

• Steroidogenic enzyme defects (17-hydroxylase)
• Ovarian resistance syndrome
• Autoimmune oophoritis
• Postinfection (eg. Mumps)
• Postoopherectomy
• Postradiation
• Postchemotherapy

84
HYPOGONADOTROPHIC HYPOGONADISM

• Normal hight
• Normal external and internal genital organs
  (infantile)
• Low FSH and LH
• MRI to intra-cranial pathology.
• 30-40 anosmia (Kallmanns syndrome)
• Sometimes ? constitutional delay
• Treat according to the cause (HRT), potentially
  fertile.

85
CONSTITUTIONAL PUBERTAL DELAY

• Common cause (20)
• Under stature and delayed bone age
• ( X-ray Wrist joint)
• Positive family history
• Diagnosis by exclusion and follow up
• Prognosis is good
• (late developer)
• No drug therapy is required - Reassurance (?
  HRT)

86
WEIGHT-RELATED AMENORRHOEAAnorexia Nervosa

• 1o or 2o Amenorrhea is often first sign
• A body mass index (BMI) lt17 kg/m²? menstrual
  irregularity and amenorrhea
• Hypothalamic suppression
• Abnormal body image, intense fear of weight gain,
  often strenuous exercise
• Mean age onset 13-14 yrs (range 10-21 yrs)
• Low estradiol ? risk of osteoporosis
• Bulemics less commonly have amenorrhea due to
  fluctuations in body wt, but crash diets can
  cause menstrual irregularity.
• Treatment ? body wt. (Psychiatrist referral)

87
EXERCISE-ASSOCIATED AMENORRHOEA

• Common in girls who participate in sports (e.g.
  competitive athletes, ballet dancers)
• Eating disorders have a higher prevalence in
  female athletes than non-athletes
• Hypothalamic disorder caused by abnormal
  gonadotrophin-releasing hormone pulsatility,
  resulting in impaired gonadotrophin levels,
  particularly LH, and subsequently low oestrogen
  levels

88
UTERO-VAGINAL AGENISIS Mayer-Rokitansky-Kuster-Ha
user syndrome

• 15 of 1ry amenorrhea
• Normal breasts and Sexual Hair development
  Normal looking external female genitalia
• Normal female range testosterone level
• Absent uterus and upper vagina normal ovaries
• Karyotype 46-XX
• 15-30 renal, skeletal and middle ear anomalies
• Treatment Vaginal creation (Dilatation vs
  Vaginoplasty)

89
ANDROGEN INSENSITIVITYTesticular feminization
syndrome

• X-linked trait
• Normal breasts but no sexual hair
• Normal looking female external genitalia
• Absent uterus and upper vagina
• Karyotype 46, XY
• Male range testosterone level
• Treatment gonadectomy after puberty HRT
• ? Vaginal creation (dilatation VS Vaginoplasty)

90
HORMONAL TREATMENTPRIMARY AMENORRHEA WITH ABSENT
SECONDARY SEXUAL CHARACTERISTICS

• To achieve pubertal development
• Premarin 5mg D1-D25 provera 10mg D15-D25 X
  3 months ? 2.5mg premarin X 3 months and
• ? 1.25mg premarin X 3 months
• Maintenance therapy
• 0.625mg premarin provera or ready HRT
  preparation or 30µg oral contraceptive pill

91
TREATMENT OF DELAYED PUBERTY

• Constitutional Reassurance.
• Treatment of the cause (if treatable) or cyclic
  estrogen-progesterone hormone replacement
  therapy. If the cause is not treatable, for 3
  cycles Norethistrone acetate 5 mg twice daily
  for 21 d or OCP
• Patient with Y chromosome cell line
  Gonadectomy hormone replacement therapy

92
Thank you