Transcript Puberty

Puberty
Clinic of Reproduction and Gynecology
Pomeranian Medical Academy
Iwona Szydłowska
It is a physiological phase
lasting 2 to 5 years, during
which the genital organs
mature
SEXUAL MATURATION
Physical, emotional and sexual transition
from childhood to adulthood
Gradually. Sequence of physiological
changes.
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.
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.
GONADARCHE
Somatic changes dependent on
gonadal sex steroid hormones
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 .
CNS-Hypothalamus-Pituitary
Ovary-Uterus Interaction
Neural control
Dopamine
(-)
Chemical control
Norepinephrine
(+)
Endorphines
(-)
Hypothalamus
±
Gn-RH
Ant. pituitary
? –
FSH, LH
Estrogen
Ovaries
Uterus
Menses
Progesterone
HYPOTHALAMUS-PITUITARY
OVARIAN 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.
The anterior pituitary responds
by progressive secretion of
FSH and LH associated with
increased secretion of growth
hormone.
The ovaries respond to the
increase Gonadotrophin
secretion by follicular
development & estrogen
secretion.
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.
SECONDARY SEX
CHARACTERS INCLUDE:
development of the breast,
appearance of pubic and
axillary hair.
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.
DEPOSITION OF SC FAT:
17% to menstruate
&
22% to ovulate
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.
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
Estradiol
10,6
Androgens
12,0
12,7
13,7
14,7
GH
Estradiol
Progesterone
Androgens
FEMALE PUBERTAL STAGES
(TANNER)
P1
P2
P3
P4
P5
Prepubertal
Early development of subareolar breast
bud +/- small amounts of pubic hair and
axillairy hair
Increase in size of palpable breast tissue
and areolae, increased amount of dark
pubic hair and/of axillary hair
Further increase in breast size and
areolae that protrude above breast level
adult pubic hair
Adult stage, pubic hair with extension to
upper thigh
TANNER’S 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)
TANNER’S 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)
GENITAL ORGANS CHANGES:
Mons pubes, labia majora & minora:
increase in size.
Vagina:
1. length: increase, appearance of the
rugae
2. epithelium: thick, stratified squamous,
containing glycogen
3. pH: acidic.
GENITAL ORGANS CHANGES:
Uterus:
enlarge, Uterus / Cervix :2 / 1
Ovaries:
1. Increase in size, almond shape
2. 300 thousands primary follicle at
menarche (2 million at birth)
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).
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).
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.
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 .
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 .
FEMALE PRECOCIOUS
PUBERTY
DEFINITION:
It means menarche or
appearance of any of the
secondary sexual characters
before the age of 8 years.
TYPES:
1 - True precocious puberty.
2 - False (pseudo-precocious
puberty).
3 - Incomplete precocious puberty.
1. TRUE (CENTRAL,CEREBRAL)
PRECOCIOUS PUBERTY.
It is due to increased production
of pituitary gonadotrophins.
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.
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)
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.
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.
PRECOCIOUS PUBERTY - TERMS
breast development - premature
thelarche,
pubic development - premature
pubarche
axillary hair development - premature
adrenarche
menses - premature menarche
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.
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.
McCune-Albright Syndrome:
The disease is found more frequently in girls.
It consists of a triad of :
1. Precocious puberty,
2. Cystic changes in bones, and
3. 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.
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.
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.
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.
DIAGNOSIS OF PRECOCIOUS
PUBERTY
1. History:
It excludes iatrogenic source of
estrogen or androgen.
It differentiates between isosexual and
heterosexual precocious puberty.
DIAGNOSIS OF PRECOCIOUS
PUBERTY
2. Physical examination:
It diagnoses McCune-Albright
syndrome.
Neurologic and ophthalmologic
examinations exclude organic lesions
of the brain.
DIAGNOSIS OF PRECOCIOUS
PUBERTY
3. Special investigations:
These are done according to the history
and clinical findings and include:
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.
3. SPECIAL INVESTIGATIONS:
b. Hormonal assay:
including serum FSH, LH, prolactin,
estradiol, testosterone, 17α-hydroxy
progesterone, TSH, and human
chorionic gonadotrophin to diagnose
Choriocarcinoma.
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.
Hypothyroidism retards bone
age and is the only
condition of precocious
puberty in which bone age is
retarded
IDIOPATHIC PRECOCIOUS
PUBERTY:
is diagnosed after excluding
all other causes.
TREATMENT OF PRECOCIOUS
PUBERTY
1.
2.
3.
4.
Objectives:
Arrest maturation until normal pubertal
age.
Attenuate & diminish established
precocious characteristics.
Maximize adult height.
Avoid abuse, reduce emotional & social
problems
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.
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.
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 (DepoProvera);
(c) Danazol capsules;
(d) Cyproterone acetate tablets (Androcur).
IDIOPATHIC TYPE
Treatment is given till the age
of 12 years (mean age of
pubertal development).
Gonadotrophin releasing hormone
analogues
Drug of choice because it achieves all objectives:
1.
2.
3.
4.
5.
6.
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 >12 yrs.
Maintain E2 at <10 pg/mL.
Children require higher doses than adults for
suppression.
Adrenarche will continue.
DELAYED PUBERTY
Secondary Sexual Characters
do not develop by the age of
14 yrs
or
no menstruation till age of 16yrs
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.
ETIOLOGY OF DELAYED PUBERTY
1 - Constitutional
with +ve family history, short stature & normal
fertility.
2 - Hypergonadotropic hypogonadism (FSH > 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.
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 .
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 .
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 .
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.
AMENORRHEA
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.
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 Asherman’s
syndrome)
EUESTROGENIC ANOVULATORY
AMENORRHEA
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
Cushing’s syndrome
Congenital adrenal
hyperplasia (late
onset)
HYPOESTROGENIC ANOVULATORY
AMENORRHEA
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
- Cushing’s syndrome
- Congenital adrenal
hyperplasia (late onset)
DIAGNOSIS
HISTORY
PHYSICAL EXAMINATION
ULTRASOUND
EXAMINATION
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
IMPERFORATE HYMEN
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
AMENORRHEA
Absent or poor secondary sex Characteristics
FSH Serum level
Low / normal
Hypogonadotropic
hypogonadim
High
Gonadal
dysgenesis
AMENORRHEA
Normal secondary sex Characteristics
- FSH, LH, Prolactin, TSH
- Provera 10 mg PO daily
x 5 days
Prolactin
 TSH
+ Bleeding
No bleeing
- Mild hypothalamic
dysfunction
- PCO (LH/FSH)
Further
Work-up
(Endocrinologist)
Review FSH result
And history (next slide)
FSH
High
Low / normal
Ovarian
failure
Hypothalamic-pituitary
Failure
If < 25 yrs or primary
amenorrhea  karyoptype
If < 35 yrs autoimmune
disease
?? Ovarian biopsy
head CT- scan or MRI
- Severe hypothalamic
dysfunction
- Intracranial pathology
AMENORRHEA
Utero-vaginal absence
Karyotype
46-XY
. Gonadal regression
. Testicular enzymes
deficiency
. Leydig cell agenisis
Absent breasts
& sexual hair
46-XX
Andogen
Insenitivity
(TFS syndrome)
Normal breasts
& absent sexual
hair
Mullerian
Agenesis
(MRKH syndrome)
Normal breasts
& sexual hair
AMENORRHEA
Signs of androgen excess
Testosterone, DHEAS, FSH, and LH
TEST. >200 ng/dL
DHEAS >700 mug/dL
Serum 17-OH
Progesterone level
U/S ? MRI or CT
Ovarian
Or adrenal
tumor
DHEAS 500-700 mug/dL
Adrenal
hyperfunction
Late CAH
Lower elevations  PCOS (High LH / FSH)
AMENORRHEA
PRIMARY AMENORRHEA
Ovarian failure
Hypogonadotrophic hypogonadism
PCOS
Congenital lesions (other than dysgenesis)
Hypopituitarism
Hyperprolactinaemia
Weight related
36%
34%
17%
4%
3%
3%
3%
GONADAL DYSGENESIS
Chromosomally incompetent
- Classic Turner’s syndrome (45XO)
- Turner variants (45XO/46XX),
(46X-abnormal X)
- Mixed gonadal dygenesis (45XO/46XY)
Chromosomally competent
- 46XX (pure gonadal dysgenesis)
- 46XY (Swyer’s syndrome)
TURNER’S 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
TURNER’S SYNDROME
(Classic 45-XO)
Mosaic (46-XX / 45-XO)
OVARIAN DYSGENESIS
NONE-DYSGENESIS
OVARIAN FAILURE
Steroidogenic enzyme defects (17hydroxylase)
Ovarian resistance syndrome
Autoimmune oophoritis
Postinfection (eg. Mumps)
Postoopherectomy
Postradiation
Postchemotherapy
HYPOGONADOTROPHIC
HYPOGONADISM
• Normal hight
• Normal external and internal
genital organs (infantile)
• Low FSH and LH
• MRI to intra-cranial
pathology.
• 30-40% anosmia (Kallmann’s
syndrome)
• Sometimes  constitutional
delay
• Treat according to the cause
(HRT), potentially fertile.
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)
WEIGHT-RELATED
AMENORRHOEA
Anorexia Nervosa
1o or 2o Amenorrhea is often first sign
A body mass index (BMI) <17 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)
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
UTERO-VAGINAL AGENISIS
Mayer-Rokitansky-Kuster-Hauser
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)
ANDROGEN INSENSITIVITY
Testicular 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)
HORMONAL TREATMENT
PRIMARY 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
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
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