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Puberty
    Dr. Ashraf Fouda
Damietta General Hospital
PUBERTY
  It is a physiological
phase lasting
    2 to 5 years,
    during which the
 genital organs mature
Manifestations of puberty
   : in the female include

1.   Menarche,
2.   Appearance of secondary sex
     characters,
3.   Physical development and
4.   Psychological changes.
Secondary sex characters
        :include

 development of the
breast, appearance of
  pubic and axillary
         hair.
The first sign of pubertal
 development is usually breast
 growth (thelarche), followed by
 appearance of pubic hair
 (pubarche), then (axillary hair),
 then (menarche).
The mean interval between breast
 budding and menarche is 2.5 years
 with a standard deviation of about
 one year.
Adrenarche
means increased activity of the
  suprarenal cortex at puberty
  with increased production of
adrenal androgens which lead
 to appearance of pubic and
          axillary hair.
: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 .
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 .
Factors affecting the initiation
    :of pubertal development

1 - Height and weight ratio (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
: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)
: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 .
True (central ,cerebral). 1
  . precocious puberty

 It is due to increased
 production of pituitary
     gonadotrophins.
False (peripheral) precocious puberty. 2

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.
False (peripheral) precocious puberty. 2

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)
Incomplete precocious puberty. 3
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.
Incomplete precocious puberty. 3

 Incomplete forms of precocious
     puberty include premature
      thelarche (unilateral or
  bilateral), premature pubarche
    and premature adrenarche
   with appearance of pubic and
            axillary hair.
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.
Etiology of precocious puberty
3. McCune-Albright syndrome.
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
  thyroid stimulating hormone and the secretion of
  pituitary gonadotrophins may also be increased.
7. Drugs:
 latrogenic 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.
8. Silver syndrome: Small stature, retarded bone age
  and increased Gonadotrophin levels.
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.
FEMALE PRECOCIOUS PUBERTY


    3. Special investigations:
 These are done according to the
   history and clinical findings
           and include:
:Special investigations. 3
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.
:Special investigations. 3
b. Hormonal assay:
 including serum FSH, LH,
 prolactin, estradiol, testosterone,
 17α-hydroxy progesterone, TSH,
 and human chorionic
 gonadotrophin to diagnose
 Choriocarcinoma.
:Special investigations. 3
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
                 Objectives:
1.   Arrest maturation until normal
     pubertal age.
2.   Attenuate & diminish established
     precocious characteristics.
3.   Maximize adult height.
4.   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. 3
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
Idiopathic type. 4
 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).
Idiopathic type. 4
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.   It acts by binding to the anterior pituitary receptors
     causing down-regulation & desensitization of the
     pituitary.
2.   Regression of symptoms occurs in the first year
3.   Delayed epiphyseal fusion; treatment more effective if
     begun before bone age >12 yrs.
4.   Maintain E2 at <10 pg/mL.
5.   Children require higher doses than adults for
     suppression.
6.   Adrenarche will continue.
: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.
Delayed Puberty

Secondary Sexual Characters
do not develop by the age of 14 y
              or
 no menstruation till age of 16y
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 disturbance).
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
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
Thank you

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Puberty

  • 1. Puberty Dr. Ashraf Fouda Damietta General Hospital
  • 2. PUBERTY It is a physiological phase lasting 2 to 5 years, during which the genital organs mature
  • 3. Manifestations of puberty : in the female include 1. Menarche, 2. Appearance of secondary sex characters, 3. Physical development and 4. Psychological changes.
  • 4. Secondary sex characters :include development of the breast, appearance of pubic and axillary hair.
  • 5. The first sign of pubertal development is usually breast growth (thelarche), followed by appearance of pubic hair (pubarche), then (axillary hair), then (menarche). The mean interval between breast budding and menarche is 2.5 years with a standard deviation of about one year.
  • 6. Adrenarche means increased activity of the suprarenal cortex at puberty with increased production of adrenal androgens which lead to appearance of pubic and axillary hair.
  • 7. :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 .
  • 8. The anterior pituitary responds by progressive secretion of FSH and LH associated with increased secretion of growth hormone .
  • 9. The ovaries respond to the increase Gonadotrophin secretion by follicular development & estrogen secretion .
  • 10. 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 .
  • 11. Factors affecting the initiation :of pubertal development 1 - Height and weight ratio (nutritional factors). 2 - Maturation of the hypothalamus . 3 - Increased neurotransmitter output in CNS . 4 - Onset of adrenal androgen activity
  • 12. :Deposition of SC fat 17% to menstruate & 22% to ovulate
  • 13. :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.
  • 14. :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)
  • 15. :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 .
  • 16. 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 .
  • 18. :Definition It means menarche or appearance of any of the secondary sexual characters before the age of 8 years.
  • 19. :Types 1 - True precocious puberty . 2 - False (pseudo-precocious puberty). 3 - Incomplete precocious puberty .
  • 20. True (central ,cerebral). 1 . precocious puberty It is due to increased production of pituitary gonadotrophins.
  • 21. False (peripheral) precocious puberty. 2 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.
  • 22. False (peripheral) precocious puberty. 2 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)
  • 23. Incomplete precocious puberty. 3 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.
  • 24. Incomplete precocious puberty. 3 Incomplete forms of precocious puberty include premature thelarche (unilateral or bilateral), premature pubarche and premature adrenarche with appearance of pubic and axillary hair.
  • 25. 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.
  • 26. 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.
  • 27. Etiology of precocious puberty 3. McCune-Albright syndrome. 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.
  • 28. 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.
  • 29. Etiology of precocious puberty 6. Juvenile hypothyroidism: Lack of thyroxine leads to increased production of thyroid stimulating hormone and the secretion of pituitary gonadotrophins may also be increased. 7. Drugs:  latrogenic 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. 8. Silver syndrome: Small stature, retarded bone age and increased Gonadotrophin levels.
  • 30. Diagnosis of precocious puberty 1. History: It excludes iatrogenic source of estrogen or androgen. It differentiates between isosexual and heterosexual precocious puberty.
  • 31. Diagnosis of precocious puberty 2. Physical examination: It diagnoses McCune-Albright syndrome. Neurologic and ophthalmologic examinations exclude organic lesions of the brain.
  • 32. FEMALE PRECOCIOUS PUBERTY 3. Special investigations: These are done according to the history and clinical findings and include:
  • 33. :Special investigations. 3 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.
  • 34. :Special investigations. 3 b. Hormonal assay: including serum FSH, LH, prolactin, estradiol, testosterone, 17α-hydroxy progesterone, TSH, and human chorionic gonadotrophin to diagnose Choriocarcinoma.
  • 35. :Special investigations. 3 c. Ultrasonography to diagnose ovarian or adrenal tumor. d. CT or MRI : to diagnose an organic lesion of the brain, or adrenal tumor.
  • 36. Hypothyroidism retards bone age, and is the only condition of precocious puberty in which bone age is retarded
  • 37. Idiopathic precocious :puberty is diagnosed after excluding all other causes.
  • 38. Treatment of precocious puberty Objectives: 1. Arrest maturation until normal pubertal age. 2. Attenuate & diminish established precocious characteristics. 3. Maximize adult height. 4. Avoid abuse, reduce emotional & social problems
  • 39. 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.
  • 40. McCune-Albright syndrome. 3 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
  • 41. Idiopathic type. 4 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).
  • 42. Idiopathic type. 4 Treatment is given till the age of 12 years (mean age of pubertal development).
  • 43. Gonadotrophin releasing hormone analogues Drug of choice because it achieves all objectives: 1. It acts by binding to the anterior pituitary receptors causing down-regulation & desensitization of the pituitary. 2. Regression of symptoms occurs in the first year 3. Delayed epiphyseal fusion; treatment more effective if begun before bone age >12 yrs. 4. Maintain E2 at <10 pg/mL. 5. Children require higher doses than adults for suppression. 6. Adrenarche will continue.
  • 44. :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.
  • 45. Delayed Puberty Secondary Sexual Characters do not develop by the age of 14 y or no menstruation till age of 16y
  • 46. 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 .
  • 47. 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 .
  • 48. 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 .
  • 49. Investigations of delayed puberty History : 1 - Family history , nutritional history , any systemic diseases (e.g. history of endocrinal disturbance). 2 - Clinical picture of space occupying lesion in the ovary , adrenal, pituitary & hypothalamus. 3 - Periodic pain and +ve 2ry sexual characteristics in imperforate hymen .
  • 50. 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 .
  • 51. :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
  • 52. 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