Dr. Ashraf Fouda Damietta General Hospital

Puberty Puberty Dr. Ashraf Fouda

Damietta General Hospital

PUBERTYPUBERTY

It is a physiological It is a physiological phase lasting phase lasting

2 to 5 years2 to 5 years, , during which the during which the

genital organs mature genital organs mature

Manifestations of puberty Manifestations of puberty in the female include in the female include::

1.1. Menarche, Menarche,

2.2. Appearance of secondary sex Appearance of secondary sex characters, characters,

3.3. Physical development and Physical development and

4.4. Psychological changes. Psychological changes.

Secondary sex characters Secondary sex characters includeinclude::

development of the development of the breast, appearance of breast, appearance of

pubic and axillary pubic and axillary hair.hair.

The first sign of pubertal The first sign of pubertal development is usually breast development is usually breast growth growth (thelarche),(thelarche), followed by followed by appearance of pubic hair appearance of pubic hair (pubarche),(pubarche), then then ((axillary hair)axillary hair), , then then ((menarche)menarche)..

The mean interval between breast The mean interval between breast budding and menarche is budding and menarche is 2.5 years2.5 years with a standard deviation of about with a standard deviation of about one yearone year..

AdrenarcheAdrenarchemeans means increased activity of the increased activity of the

suprarenal cortex at pubertysuprarenal cortex at puberty with increased production of with increased production of

adrenal androgens which lead adrenal androgens which lead to appearance of pubic and to appearance of pubic and

axillary hair.axillary hair.

Cause of pubertyCause of puberty: : During childhood , the During childhood , the hypothalamus is hypothalamus is

extremely sensitive to the negative feedbackextremely sensitive to the negative feedback exerted by the small quantities of estradiol exerted by the small quantities of estradiol & testosterone produced by the child's & testosterone produced by the child's ovaries . ovaries .

As puberty approaches , As puberty approaches , the sensitivity of the sensitivity of the hypothalamus is decreasedthe hypothalamus is decreased and and subsequentlysubsequently , it , it increase the pulsatile increase the pulsatile GnRH secretion .GnRH secretion .

The anterior pituitary The anterior pituitary responds by progressive responds by progressive secretion of secretion of FSH and LHFSH and LH

associated with associated with increased secretion of increased secretion of

growth hormonegrowth hormone . .

The The ovaries respondovaries respond to to the increase the increase

Gonadotrophin secretion Gonadotrophin secretion by by follicular follicular

development & estrogen development & estrogen secretion .secretion .

EstrogenEstrogen causes development causes development of the genital organs and the of the genital organs and the appearance of the secondary appearance of the secondary sexual characters . sexual characters .

With increased estrogen With increased estrogen secretion , secretion , menarchemenarche and and cyclic estrogen secretion cyclic estrogen secretion occurs .occurs .

Factors affecting the Factors affecting the initiation of pubertal initiation of pubertal

developmentdevelopment: :

1 - 1 - Height and weight ratioHeight and weight ratio (nutritional (nutritional factors).factors).

2 - Maturation of the 2 - Maturation of the hypothalamushypothalamus . .

3 - Increased 3 - Increased neurotransmitter outputneurotransmitter output in CNS .in CNS .

4 - Onset of 4 - Onset of adrenal androgenadrenal androgen activity activity

Deposition of SC fatDeposition of SC fat::

17%17% to menstruate to menstruate & &

22%22% to ovulate to ovulate

Genital organs Genital organs changeschanges::

Mons pubes, labia majora & minoraMons pubes, labia majora & minora:: increase in size. increase in size.

Vagina:Vagina:1.1. length:length: increase, appearance of the increase, appearance of the

rugaerugae2.2. Epithelium:Epithelium: thick, stratified thick, stratified

squamous., containing glycogensquamous., containing glycogen3.3. pH:pH: acidic. acidic.

UterusUterus:: enlarge, Uterus / Cervix :2 / 1enlarge, Uterus / Cervix :2 / 1Ovaries:Ovaries:1.1.Increase in size, almond shapeIncrease in size, almond shape2.2.300 thousands primary follicle at 300 thousands primary follicle at

menarche ( 2 million at birth) menarche ( 2 million at birth)

Genital organs Genital organs changeschanges::

AdolescenceAdolescence: : Is the period of life during which Is the period of life during which

the child becomes an adult personthe child becomes an adult person

i.e. the physical , sexual and i.e. the physical , sexual and psychological development are psychological development are

complete . complete . Puberty represents the first part Puberty represents the first part

of adolescence .of adolescence .

Abnormalities of pubertyAbnormalities of puberty

1 - 1 - Precocious puberty .

2 - Delayed puberty .

3 3 - Growth problems :

during adolescence e.g. short during adolescence e.g. short stature or tall stature , marked stature or tall stature , marked

obesity and menstrual disorders obesity and menstrual disorders at puberty .at puberty .

FEMALE FEMALE PRECOCIOUS PRECOCIOUS

PUBERTYPUBERTY

DefinitionDefinition::It means menarche or It means menarche or appearance of any of appearance of any of the secondary sexual the secondary sexual characters before the characters before the

age of age of 8 years.8 years.

TypesTypes::

1 1 - - TrueTrue precocious puberty .precocious puberty .

2 2 - - FalseFalse (pseudo-precocious puberty).(pseudo-precocious puberty).

3 3 -- IncompleteIncomplete precocious precocious puberty .puberty .

11 . .True (central ,cerebral) True (central ,cerebral) precocious pubertyprecocious puberty . .

It is due to increased It is due to increased production of pituitary production of pituitary

gonadotrophins.gonadotrophins.

22 . .False (peripheral) precocious False (peripheral) precocious pubertypuberty

It is of peripheral origin. It is of peripheral origin. It is It is due to secretion of sex due to secretion of sex

hormoneshormones; ; (estrogen or androgen)(estrogen or androgen) which is not dependent on which is not dependent on pituitary gonadotrophins as in pituitary gonadotrophins as in case of estrogenic or androgenic case of estrogenic or androgenic ovarian tumors. ovarian tumors.

False precocious puberty may be False precocious puberty may be isosexual or heterosexual.isosexual or heterosexual.

A girl who feminizes early is defined as A girl who feminizes early is defined as having having isosexual precocious pubertyisosexual precocious puberty. .

A girl who virilize early is defined as A girl who virilize early is defined as having having heterosexual precocious pubertyheterosexual precocious puberty.. (female pseudohermaphrodite)(female pseudohermaphrodite)

22 . .False (peripheral) precocious False (peripheral) precocious pubertypuberty

33 . .Incomplete precocious Incomplete precocious pubertypuberty

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

The other pubertal changes occur at The other pubertal changes occur at the normal age. the normal age.

Incomplete forms of precocious Incomplete forms of precocious puberty include puberty include premature premature

thelarchethelarche (unilateral or (unilateral or bilateral), bilateral), premature pubarchepremature pubarche

and and premature adrenarchepremature adrenarche with appearance of pubic and with appearance of pubic and

axillary hair.axillary hair.

33 . .Incomplete precocious Incomplete precocious pubertypuberty

Etiology of precocious Etiology of precocious pubertypuberty

1.Constitutional or idiopathic:1.Constitutional or idiopathic: In most cases of precocious puberty In most cases of precocious puberty

(90%)(90%) , no cause is found. , no cause is found. For some unknown reason the For some unknown reason the

hypothalamus stimulates the pituitary hypothalamus stimulates the pituitary gland to secrete its gonadotrophic gland to secrete its gonadotrophic hormones. hormones.

There is normal menstruation and There is normal menstruation and ovulation. ovulation.

Pregnancy can occur at young age.Pregnancy can occur at young age.

2. 2. Organic lesions of the brain:Organic lesions of the brain: The next common cause. The next common cause. Organic lesionsOrganic lesions affecting the midbrain, affecting the midbrain,

hypothalamus, pineal body, or pituitary gland hypothalamus, pineal body, or pituitary gland may lead to premature release of pituitary may lead to premature release of pituitary gonadotrophins. gonadotrophins.

ExamplesExamples include traumatic brain injury, include traumatic brain injury, meningitis, encephalitis, brain abscess, brain meningitis, encephalitis, brain abscess, brain tumor as glioma, craniopharyngioma, and tumor as glioma, craniopharyngioma, and hamartomas.hamartomas.


3. McCune-Albright syndrome.3. McCune-Albright syndrome.4. Adrenal causes:4. Adrenal causes: (a) Hyperplasia, adenoma, or (a) Hyperplasia, adenoma, or

carcinoma of suprarenal cortex. carcinoma of suprarenal cortex. Congenital adrenal hyperplasia and Congenital adrenal hyperplasia and Cushing syndromeCushing syndrome lead to precocious lead to precocious

puberty in the male direction, i.e. puberty in the male direction, i.e. heterosexual precocious puberty; heterosexual precocious puberty;

(b) Estrogen secreting adrenal tumor (b) Estrogen secreting adrenal tumor which is very rare.which is very rare.


5. Ovarian causes5. Ovarian causes : :(a) (a) Estrogen producing tumorsEstrogen producing tumors as granulosa as granulosa

and theca cell tumor; and theca cell tumor;

(b) (b) Androgen producing tumorsAndrogen producing tumors as as androblastoma; androblastoma;

(c) (c) ChoriocarcinomaChoriocarcinoma because it secretes human because it secretes human chorionic gonadotrophin (HCG) which may chorionic gonadotrophin (HCG) which may stimulate the ovaries to secrete estrogen; stimulate the ovaries to secrete estrogen;

(d) (d) Dysgerminoma Dysgerminoma if it secretes HCG.if it secretes HCG.


6. 6. Juvenile hypothyroidism:Juvenile hypothyroidism: Lack of thyroxine leads to increased production of Lack of thyroxine leads to increased production of

thyroid stimulating hormone and the secretion of thyroid stimulating hormone and the secretion of pituitary gonadotrophins may also be increased.pituitary gonadotrophins may also be increased.

7. 7. Drugs:Drugs: latrogenic may follow oral or local administration latrogenic may follow oral or local administration

of estrogen. of estrogen. A long course of estrogen cream used for treatment A long course of estrogen cream used for treatment

of vulvovaginitis of children may lead to breast of vulvovaginitis of children may lead to breast development or withdrawal bleeding.development or withdrawal bleeding.

8. 8. Silver syndrome:Silver syndrome: Small stature, retarded bone age Small stature, retarded bone age and increased Gonadotrophin levels.and increased Gonadotrophin levels.

Etiology of precocious pubertyEtiology of precocious puberty

1. History:1. History: It excludes iatrogenic source of It excludes iatrogenic source of

estrogen or androgen. estrogen or androgen. It differentiates between It differentiates between

isosexual and heterosexual isosexual and heterosexual precocious puberty.precocious puberty.

Diagnosis of precocious Diagnosis of precocious pubertypuberty

2. Physical examination:2. Physical examination: It diagnoses McCune-Albright It diagnoses McCune-Albright

syndrome. syndrome. Neurologic and ophthalmologic Neurologic and ophthalmologic

examinations exclude organic examinations exclude organic lesions of the brain.lesions of the brain.

Diagnosis of precocious Diagnosis of precocious pubertypuberty

3. Special investigations:3. Special investigations:

These are done according to the These are done according to the history and clinical findings history and clinical findings

and include: and include:

FEMALE PRECOCIOUS PUBERTYFEMALE PRECOCIOUS PUBERTY

a. a. X-ray examination of the hand and wristX-ray examination of the hand and wrist to determine bone age. to determine bone age.

Estrogen stimulates growth of bone but Estrogen stimulates growth of bone but causes early fusion of the epiphysis. causes early fusion of the epiphysis.

So the child is taller than her peers during So the child is taller than her peers during childhood, but she is short during adult childhood, but she is short during adult life. life.

33 . .Special investigationsSpecial investigations::

b. b. Hormonal assay:Hormonal assay: including serum FSH, LH, including serum FSH, LH, prolactin, estradiol, testosterone, prolactin, estradiol, testosterone, 1717αα--hydroxy progesterone, TSH, , TSH, and human chorionic and human chorionic gonadotrophingonadotrophin to diagnose to diagnose Choriocarcinoma.Choriocarcinoma.


cc.. Ultrasonography Ultrasonography to diagnose ovarian or adrenal to diagnose ovarian or adrenal tumor. tumor.

d.d. CT or MRICT or MRI : : to diagnose an organic lesion to diagnose an organic lesion of the brain, or adrenal tumor.of the brain, or adrenal tumor.


Hypothyroidism Hypothyroidism retards bone age, retards bone age, and is the only condition and is the only condition of precocious puberty in of precocious puberty in

which bone age is which bone age is retarded retarded

is diagnosed after is diagnosed after excluding all other excluding all other

causes.causes.

Idiopathic precociousIdiopathic precocious pubertypuberty::

Treatment of precocious Treatment of precocious pubertypubertyObjectives:Objectives:

1.1. Arrest maturation until normal Arrest maturation until normal pubertal age. pubertal age.

2.2. Attenuate & diminish established Attenuate & diminish established precocious characteristics.precocious characteristics.

3.3. Maximize adult height.Maximize adult height.

4.4. Avoid abuse, reduce emotional & Avoid abuse, reduce emotional & social problemssocial problems

1. 1. Treatment of the causeTreatment of the cause, e.g., , e.g., thyroxin for hypothyroidism, thyroxin for hypothyroidism, removal of ovarian and adrenal removal of ovarian and adrenal tumors.tumors.

2. 2. Incomplete formsIncomplete forms of precocious of precocious puberty do not require treatment, puberty do not require treatment, as estrogen production is not as estrogen production is not increased.increased.

Treatment of precocious Treatment of precocious pubertypuberty

33 . .McCune-Albright McCune-Albright syndromesyndrome

is treated with is treated with testolactonetestolactone oral tablets. oral tablets. The drug inhibits the formation of The drug inhibits the formation of

estrogen from its precursors, so reduces estrogen from its precursors, so reduces estrogen level. estrogen level.

The dose is The dose is 20 mg/kg20 mg/kg body weight in body weight in 4 4 divided dosesdivided doses and increased to and increased to 40 mg/kg40 mg/kg body weight during a body weight during a 3 week3 week interval. interval.

44 . .Idiopathic typeIdiopathic typeis treated by explanation and reassurance and is treated by explanation and reassurance and

by giving one of the following drugs which by giving one of the following drugs which inhibit the secretion of gonadotrophins:inhibit the secretion of gonadotrophins:

(a)(a)Gonadotrophin releasing hormone analoguesGonadotrophin releasing hormone analogues which are given as daily nasal spray, intramuscular, which are given as daily nasal spray, intramuscular, or subcutaneous injections every 4 weeks. or subcutaneous injections every 4 weeks.

(b)Medroxyprogesterone acetate tablets(b)Medroxyprogesterone acetate tablets (Provera (Provera tablets) or intramuscular injection (Depo-Provera); tablets) or intramuscular injection (Depo-Provera);

(c) Danazol(c) Danazol capsules; capsules;

(d) Cyproterone acetate(d) Cyproterone acetate tablets (Androcur). tablets (Androcur).

Treatment is given till Treatment is given till the age of 12 years the age of 12 years

(mean age of pubertal (mean age of pubertal development).development).

44 . .Idiopathic typeIdiopathic type

Gonadotrophin releasing hormone Gonadotrophin releasing hormone analoguesanalogues

Drug of choice because it achieves all objectives:Drug of choice because it achieves all objectives:1.1. It acts by binding to the anterior pituitary receptors It acts by binding to the anterior pituitary receptors

causing down-regulation & desensitization of the causing down-regulation & desensitization of the pituitary. pituitary.

2.2. Regression of symptoms occurs in the first yearRegression of symptoms occurs in the first year3.3. Delayed epiphyseal fusion; treatment more effective if Delayed epiphyseal fusion; treatment more effective if

begun before bone age >12 yrs. begun before bone age >12 yrs. 4.4. Maintain E2 at <10 pg/mL. Maintain E2 at <10 pg/mL. 5.5. Children require higher doses than adults for Children require higher doses than adults for

suppression. suppression. 6.6. Adrenarche will continue. Adrenarche will continue.

McCune-Albright SyndromeMcCune-Albright Syndrome:: The disease is found more frequently in girls. The disease is found more frequently in girls. It consists of a triad of :It consists of a triad of :

1.1. Precocious puberty, Precocious puberty,

2.2. Cystic changes in bones, and Cystic changes in bones, and

3.3. Cafe-au lait patches of the skin.Cafe-au lait patches of the skin. The cause of precocious puberty is autonomous The cause of precocious puberty is autonomous

production of estrogen by the ovaries. production of estrogen by the ovaries. FSH and LH levels are lowFSH and LH levels are low. . The treatment is The treatment is testolactonetestolactone oral tablets which oral tablets which

inhibit ovarian steroidogenesis.inhibit ovarian steroidogenesis.

Delayed PubertyDelayed Puberty

Secondary Sexual Characters Secondary Sexual Characters do not develop by the age of do not develop by the age of 14 y14 y

or or

no menstruation till age of no menstruation till age of 16y16y

It is either :It is either :

* * Delayed onset:Delayed onset: Breast bud does not Breast bud does not appear till 13 years or menarche does appear till 13 years or menarche does not occur till 16 years . ornot occur till 16 years . or

* * Delayed progreessionDelayed progreession : : Menarche Menarche does not occur within 5 years after does not occur within 5 years after breast bud . breast bud .

Delayed PubertyDelayed Puberty

Etiology of delayed pubertyEtiology of delayed puberty1 -1 - ConstitutionalConstitutional

with +ve family history , short stature & with +ve family history , short stature & normal fertility .normal fertility .

2 -2 - Hypergonadotropic hypogonadismHypergonadotropic hypogonadism (FSH > 40) = ovarian causes of Iry (FSH > 40) = ovarian causes of Iry amenorrhea = primary ovarian failure & 2ry amenorrhea = primary ovarian failure & 2ry ovarian failure (if occurs before puberty).ovarian failure (if occurs before puberty).

3 -3 - Hypogonadtropic hypogonadismHypogonadtropic hypogonadism = = hypothalamic & pituitary causes of Iry hypothalamic & pituitary causes of Iry amenorrhea e.g. Kallman's syndrome , amenorrhea e.g. Kallman's syndrome , Anorexia nervosa .Anorexia nervosa .

4 - 4 - Normogonadtropic hypogonadismNormogonadtropic hypogonadism = end organ defects = uterine causes= end organ defects = uterine causes (Mullerian agenesis and testicular (Mullerian agenesis and testicular feminization syndrome), imperforate hymen feminization syndrome), imperforate hymen (c/o = delayed menarche + normal other (c/o = delayed menarche + normal other aspects of puberty), PCOD and Virilizing aspects of puberty), PCOD and Virilizing ovarian adrenal tumors .ovarian adrenal tumors .

5 - 5 - General causes of amenorrheaGeneral causes of amenorrhea (endocrinal or non-endocrinal especially (endocrinal or non-endocrinal especially malnutrition) if occurred before puberty malnutrition) if occurred before puberty &&↓↓GH & steroid synthesis defects .GH & steroid synthesis defects .

Etiology of delayed pubertyEtiology of delayed puberty

Investigations of delayed Investigations of delayed pubertypuberty

History :History :1 - Family 1 - Family historyhistory , nutritional history , any , nutritional history , any

systemic diseases systemic diseases (e.g. history of endocrinal disturbance).(e.g. history of endocrinal disturbance).2 - 2 - Clinical pictureClinical picture of space occupying of space occupying

lesion in the ovary , adrenal, pituitary & lesion in the ovary , adrenal, pituitary & hypothalamus.hypothalamus.

3 - Periodic pain and +ve 2ry sexual 3 - Periodic pain and +ve 2ry sexual characteristics in imperforate hymen . characteristics in imperforate hymen .

Examination :Examination :(A) (A) Body measurementBody measurement for causes of for causes of

amenorrhea + amenorrhea + ↑↑or or ↓↓weight, short or tall weight, short or tall stature , proportions (upper / lower segment stature , proportions (upper / lower segment ratio & arm span / height ratio).ratio & arm span / height ratio).

(B) (B) Tanner stagingTanner staging of breast, pubic & axillary of breast, pubic & axillary hair if present.hair if present.

(C) (C) Clinical pictureClinical picture of Turner , Mullerian of Turner , Mullerian agenesis & imperforate hymen .agenesis & imperforate hymen .

(D) (D) Neurological examinationNeurological examination for smell sense for smell sense (Kallman's syndrome), visual field & other (Kallman's syndrome), visual field & other cranial nerve lesions .cranial nerve lesions .

Investigations of delayed Investigations of delayed pubertypuberty

Special InvestigationsSpecial Investigations: : 1 - 1 - FSH & LH assayFSH & LH assay important to important to

differentiate level of the lesion & differentiate level of the lesion & progesterone assay in 17 OH progesterone assay in 17 OH deficiency .deficiency .

2 - 2 - Chromosomal studyChromosomal study if short stature if short stature or hypergonadotropic type .or hypergonadotropic type .

3 - 3 - Radiological bone ageRadiological bone age study & study & radiologic study for pituitary adenoma radiologic study for pituitary adenoma

Treatment of delayed Treatment of delayed pubertypuberty

* * Constitutional :Constitutional : Reassurance . Reassurance .* Treatment of the cause* Treatment of the cause (if treatable) or (if treatable) or

cyclic estrogen-progesterone hormone cyclic estrogen-progesterone hormone replacement therapy if the cause is not replacement therapy if the cause is not treatable , for 3 cycles: Norethistrone treatable , for 3 cycles: Norethistrone acetate 5 mg twice daily for 21 d or acetate 5 mg twice daily for 21 d or OCPOCP

* * Patient with Patient with Y chromosome cell line Y chromosome cell line :: Gonadectomy + hormone replacement Gonadectomy + hormone replacement therapy therapy

Thank youThank you

Dr. Ashraf Fouda Damietta General Hospital

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