puberty. definition of puberty it is the physiological stage that leads to reproductive capability...

Puberty Puberty

Definition of puberty Definition of puberty

It is the physiological stage that leads It is the physiological stage that leads to reproductive capability manifested to reproductive capability manifested by spermatogenesis in the male and by spermatogenesis in the male and ovulation in the female. ovulation in the female.

Conditions influence the age onset Conditions influence the age onset of pubertyof puberty

1.1. Socioeconomic conditions Socioeconomic conditions

2.2. Nutritional statusNutritional status

3.3. States of health States of health

4.4. Chronic disease Chronic disease

5.5. Altitudes Altitudes

6.6. Genetic factors Genetic factors

7.7. Strenuous physical activity Strenuous physical activity

Female secondary sex Female secondary sex characteristicscharacteristics

1.1. Breast enlargement the first sign of Breast enlargement the first sign of puberty in % 85 girlspuberty in % 85 girls

2.2. Pubic hairPubic hair

3.3. Axillary hair Axillary hair

4.4. Vagina and uterus Vagina and uterus

5.5. Menarche (stage 4), mean age 12.8 Menarche (stage 4), mean age 12.8 yearsyears

Male secondary sex characteristics Male secondary sex characteristics

1.1. External genitalia External genitalia

2.2. Pubic hairPubic hair

3.3. Axillary and facial hair Axillary and facial hair

4.4. Voice change Voice change

5.5. Spermarche Spermarche

Changes in body size and shapeChanges in body size and shape

1. Stature: PVH1. Stature: PVH F stage IIIF stage III

M stage IV M stage IV

2. Bone age 2. Bone age

3. Body composition 3. Body composition

4. Body build proportions 4. Body build proportions

5. Strength 5. Strength

Precocious puberty Precocious puberty

Appearance of any sign of secondary Appearance of any sign of secondary sexual maturation at an age more sexual maturation at an age more than 2SD below the mean.than 2SD below the mean.

The age of 7y in girls and 9y in boysThe age of 7y in girls and 9y in boys

Precocious pubertyPrecocious puberty

True P. puberty True P. puberty Pseudo P. puberty Pseudo P. puberty Contrasexual precocity Contrasexual precocity

True precocious puberty True precocious puberty

Idiopathic true precocious pubertyIdiopathic true precocious puberty CNS tumorsCNS tumors Other CNS disorders Other CNS disorders After late treatment of C.A.H.After late treatment of C.A.H.

or previous chronic exposure to or previous chronic exposure to gonadal steroids gonadal steroids

Idiopathic precocious puberty Idiopathic precocious puberty

Most often sporadic, rarely A.R.Most often sporadic, rarely A.R. Is more common in girls Is more common in girls Progression of secondary sexual Progression of secondary sexual

maturation is often more rapid than maturation is often more rapid than normal pubertynormal puberty

There is increased risk for the There is increased risk for the development of Ca. of breast in development of Ca. of breast in adulthhood adulthhood

Ht. velocity, somatic development, Ht. velocity, somatic development, skeletal maturation are increased . skeletal maturation are increased .

Treatment of true P.P Treatment of true P.P

Medroxyprogesterone acetate Medroxyprogesterone acetate Cyproterone acetateCyproterone acetate The drug of choice is LHRH agonistsThe drug of choice is LHRH agonists

Objectives of the managements Objectives of the managements and treatment of T.P.Pand treatment of T.P.P

Detection and treatment of an expanding Detection and treatment of an expanding intracranial lesionintracranial lesion

Arrest of premature sexual maturation Arrest of premature sexual maturation Regression of secondary sexual Regression of secondary sexual

characteristicscharacteristics Attainment of normal mature heightAttainment of normal mature height Reduction of risk of sexual abuse Reduction of risk of sexual abuse Prevention of pregnancy in girlsPrevention of pregnancy in girls Preservation of future fertility Preservation of future fertility Diminish the increased risk of breast Diminish the increased risk of breast

cancer cancer

Action of LHRH agonists in TPPAction of LHRH agonists in TPP A selective highly specific A selective highly specific Pharmacological clamp on the secretion of Pharmacological clamp on the secretion of

gonadotropin gonadotropin Chronic administration induces Chronic administration induces

desensitization of the pituitary desensitization of the pituitary gonadotrope to the action of endogenous gonadotrope to the action of endogenous LHRH.LHRH.

As a consequence:As a consequence: Inhibition of pulsatile secretion of LH and Inhibition of pulsatile secretion of LH and

FSHFSH Inhibition of gonadotropin secretion Inhibition of gonadotropin secretion

Indications for therapy with LHRH Indications for therapy with LHRH agonists in T.P.Pagonists in T.P.P

In children with endocrine features of In children with endocrine features of T.P.PT.P.P

Rapid advancement over a period of 6 Rapid advancement over a period of 6 mo to 1 ymo to 1 y

A serum testosterone concentration > A serum testosterone concentration > 1ng/mL in boys less than 8 y of age1ng/mL in boys less than 8 y of age

Onset of menarche in girls less than 9 Onset of menarche in girls less than 9 y of age y of age

Side effect of LHRH agonists Side effect of LHRH agonists

Erythema (most common), sterile abscess Erythema (most common), sterile abscess and hematoma at the site of injection and hematoma at the site of injection

Anaphylactic reaction (rare)Anaphylactic reaction (rare) Asthma attack (nasal route)Asthma attack (nasal route) Bone demineralization in girlsBone demineralization in girls Antibody formation Antibody formation Acceleration of sexual precocity Acceleration of sexual precocity Diarrhea, constipation Diarrhea, constipation

Pseudo-precocious puberty Pseudo-precocious puberty (In boys)(In boys)

1.1. Gonadotropin – secreting tumorsGonadotropin – secreting tumorsInside CNS Inside CNS Outside CNSOutside CNS

2. Increase androgen secretion by adrenal or 2. Increase androgen secretion by adrenal or testistestisC.A.H.C.A.H.Virilizing adrenal tumorVirilizing adrenal tumorLeydig cell adenomaLeydig cell adenomaFamilial testotoxicosis Familial testotoxicosis

Pseudo-precocious pubertyPseudo-precocious puberty(In girls)(In girls)

Estrogen – secreting ovarian or Estrogen – secreting ovarian or adrenal neoplasm adrenal neoplasm

Ovarian cystOvarian cyst Peutz – jeghers synd. Peutz – jeghers synd.

Pseudo – precocious puberty Pseudo – precocious puberty (In both sexes)(In both sexes)

McCune – Albright synd. McCune – Albright synd. Hypothyroidism Hypothyroidism Iatrogenic or exogenous Iatrogenic or exogenous

McCune – Albright synd.McCune – Albright synd.

Café au – lait spotsCafé au – lait spots Polystotic fibrous dysplasia Polystotic fibrous dysplasia Endocrine hyperfunction Endocrine hyperfunction

Contrasexual precocity Contrasexual precocity

Feminization in boys and virilization in Feminization in boys and virilization in girls girls

Feminization in malesFeminization in males

Adrenal neoplasm Adrenal neoplasm Chorioepithelioma Chorioepithelioma 11-11-ββ hydroxylase def. hydroxylase def. Late-onset C.A.H.Late-onset C.A.H. Testicular neoplasm (peutz-jeghers synd.)Testicular neoplasm (peutz-jeghers synd.) ↑↑Extraglandular conversion adrenal Extraglandular conversion adrenal

androgens to estrogen androgens to estrogen Iatrogenic (exposure to estroges) Iatrogenic (exposure to estroges)

Virilization in girls Virilization in girls

C.A.H. (21-, 11-, 3 C.A.H. (21-, 11-, 3 HSD def.) HSD def.) Virilizing adrenal neoplasm Virilizing adrenal neoplasm Virilizing ovarian neoplasmVirilizing ovarian neoplasm Iatrogenic (exposure to androgens)Iatrogenic (exposure to androgens)

Variation of pubertal development Variation of pubertal development

Premature thelarche Premature thelarche Premature adrenarche Premature adrenarche Premature menarche Premature menarche Adolescent gynecomastia in boys Adolescent gynecomastia in boys

Classification of delayed puberty Classification of delayed puberty

Idiopathic Idiopathic

Hypogonadothropic hypogonadismHypogonadothropic hypogonadism

Hypergonadothropic hypogonadismHypergonadothropic hypogonadism

Hypogonadoropic hypogonadismHypogonadoropic hypogonadism

CNS disorders CNS disorders

TumorsTumors

Congenital malformationsCongenital malformations

Radiation therapy Radiation therapy

Head trauma Head trauma

Other causesOther causes


Isolated gonadotropin deficiency Isolated gonadotropin deficiency Kallmann syndrome with hyposmia or Kallmann syndrome with hyposmia or

anosmia anosmia Congenital adrenal hypoplasia Congenital adrenal hypoplasia Other disorders Other disorders

Idiopathic and genetic forms of multiple pituitary Idiopathic and genetic forms of multiple pituitary Hormone deficiencies Hormone deficiencies Miscellaneous disordersMiscellaneous disordersPrader-willi syndromePrader-willi syndromeLaurence-moon-biedl syndrome Laurence-moon-biedl syndrome

Characteristics of isolated Characteristics of isolated gonadotropin deficiency gonadotropin deficiency

Males more commonly affected Males more commonly affected Familial or sporadic Familial or sporadic Height normal Height normal Eunuchoid skeletal proportions Eunuchoid skeletal proportions Delayed bone age Delayed bone age Small testes: diameter ≤ 2.5 cmSmall testes: diameter ≤ 2.5 cmNormal adrenarche Normal adrenarche Examine for anosmia or hyposmia (kallmann Examine for anosmia or hyposmia (kallmann

syndrome)syndrome)Look for associated malformations (facial, Look for associated malformations (facial,

skeletal, renal) skeletal, renal)

Features of Kallmann syndromeFeatures of Kallmann syndrome

Clinical Clinical

LHRH deficiency: absent or arrested pubertyLHRH deficiency: absent or arrested puberty

Anosmia or hyposmia Anosmia or hyposmia

In infancy: microphallus, cryptorchidism In infancy: microphallus, cryptorchidism

Normal stature and growth in childhoodNormal stature and growth in childhood

Normal adrenarche Normal adrenarche

Eunuchoid proportions Eunuchoid proportions

Associated midline defectsAssociated midline defects

MRI: aplasia or hypoplasia of olfactory bulbs MRI: aplasia or hypoplasia of olfactory bulbs

Cont. Cont.

Features of Kallmann syndrome Features of Kallmann syndrome

Prevalence: approximately 1 in 7500 males, Prevalence: approximately 1 in 7500 males, 1 in 50000 females1 in 50000 females

Inheritance: sporadic and familial cases; Inheritance: sporadic and familial cases; genetic heterogeneity X linked genetic heterogeneity X linked

X-linkes recessive X-linkes recessive

X chromosome deletion: Xp22.3X chromosome deletion: Xp22.3

Autosomal (Dominat, recessive)Autosomal (Dominat, recessive)

Anatomy: developmental field defectAnatomy: developmental field defect

Aplasia or hypoplasia of olfactory bulb Aplasia or hypoplasia of olfactory bulb


Functional gonadotropin deficiency Functional gonadotropin deficiency Chronic systemic disease and malnutrition Chronic systemic disease and malnutrition

Hypothyroidism Hypothyroidism Diabetes mellitusDiabetes mellitusCushing disease Cushing disease Hyperprolactinemia Hyperprolactinemia Anorexia nervosaAnorexia nervosaPsychogenic amenorrheaPsychogenic amenorrheaDelayed puberty and/or menarche, especially in Delayed puberty and/or menarche, especially in female athletes and ballet dancersfemale athletes and ballet dancers

Cont.Cont.


Hypergonadotropic hypogonadims Hypergonadotropic hypogonadims MalesMalesKlinefelter syndrome Klinefelter syndrome Other forms of primary testicular failure Other forms of primary testicular failure

ChemotherapyChemotherapyRadiation therapy Radiation therapy LH resistance LH resistance Testicular biosynthetic defectsTesticular biosynthetic defectsAnorchia and cryptorchidims Anorchia and cryptorchidims

Cont.Cont.


Females Females Turner syndromeTurner syndrome46 XX and 46 XY gonadal dysgenesis 46 XX and 46 XY gonadal dysgenesis

Other forms of primary ovarian failure Other forms of primary ovarian failure Premature menopause Premature menopause Radiation therapy Radiation therapy Chemotherapy Chemotherapy Autoimmune oophoritis Autoimmune oophoritis Polycystic ovary disease Polycystic ovary disease Galactosemia Galactosemia

Endocrine diagnosis of constitutional Endocrine diagnosis of constitutional delayed adolescence and hypogonadotropic delayed adolescence and hypogonadotropic

hypogonadism hypogonadism

No single test reliably discriminates No single test reliably discriminates between the two diagnoses between the two diagnoses

Onset of puberty in boys is indicated Onset of puberty in boys is indicated by testes > 2.5 cm in diameter by testes > 2.5 cm in diameter

Serum testosterone concentration > Serum testosterone concentration > 50 ng/dl50 ng/dl

Pubertal LH response to LHRH bolus Pubertal LH response to LHRH bolus

Pubertal pattern of LH pulsatility Pubertal pattern of LH pulsatility

Endocrine and imaging studies in Endocrine and imaging studies in delayed adolescence delayed adolescence

Initial assessment Initial assessment Plasma testosterone or estradiol Plasma testosterone or estradiol Plasma FSH and LHPlasma FSH and LH Plasma thyroxine (and prolaction)Plasma thyroxine (and prolaction) Bone age and lateral skull roentgenograph Bone age and lateral skull roentgenograph Test of olfaction Test of olfaction

Cont.Cont.

Endocrine and imaging studies in Endocrine and imaging studies in delayed adolescencedelayed adolescence

Follow-up studies Follow-up studies Karyotype (short, phenotypic females)Karyotype (short, phenotypic females) MRI and/or CT scan MRI and/or CT scan Pelvic sonography (females)Pelvic sonography (females) LHRH testLHRH test hCG test (males)hCG test (males) Pattern of pulsatile LH secretion Pattern of pulsatile LH secretion Visual acuity and visual fields Visual acuity and visual fields

Objectives in management and Objectives in management and treatment and therapy of delayed treatment and therapy of delayed

adolescence adolescence ObjectivesObjectives

determine site and etiology of abnormality induce determine site and etiology of abnormality induce and maintain secondary sexual characteristics and maintain secondary sexual characteristics induce pubertal growth spurtinduce pubertal growth spurtprevent the potential short-term and long-termprevent the potential short-term and long-termPsychological, personality and social handicaps of Psychological, personality and social handicaps of delayed puberty delayed puberty Ensure normal libido and potency Ensure normal libido and potency Attain fertility Attain fertility

Cont.Cont.

Therapy of delayed puberty Therapy of delayed puberty

TherapyTherapyReassurance and follow-upReassurance and follow-upRepeat evaluation (including serum Repeat evaluation (including serum

testosterone or estradiol) in 6 motestosterone or estradiol) in 6 moPsychosocial handicaps, anxiety, highly Psychosocial handicaps, anxiety, highly

concerned:concerned:Therapy for 4 mo withTherapy for 4 mo withBoys: testosterone enanthate 100 mg IM every Boys: testosterone enanthate 100 mg IM every

4 wk at 14-14.5 y of age. 4 wk at 14-14.5 y of age. Girls: ethiyl estradiol 5-10 ug daily by mouth or Girls: ethiyl estradiol 5-10 ug daily by mouth or

conjugated estrogens 0.3 mg daily by mouth conjugated estrogens 0.3 mg daily by mouth at 13 y of age at 13 y of age

Hormonal substitution therapy in Hormonal substitution therapy in boys with hypogonadism boys with hypogonadism

Goal: to approximate normal adolescent Goal: to approximate normal adolescent development when diagnosis is established development when diagnosis is established

Initial therapy: at 13 y of age, testosterone Initial therapy: at 13 y of age, testosterone enanthate 50 mg IM every month for about 9 mo enanthate 50 mg IM every month for about 9 mo (6-12 mo)(6-12 mo)

Over the next 3 to 4 y: gradually increase dose to Over the next 3 to 4 y: gradually increase dose to adult replacement dose of 200 mg every 2-3wk adult replacement dose of 200 mg every 2-3wk

Begin replacement therapy in boys with Begin replacement therapy in boys with suspected hypogonadotropic hypogonadism by suspected hypogonadotropic hypogonadism by bone age < 14 ybone age < 14 y

To induce fertility at appropriate time: pulsatile To induce fertility at appropriate time: pulsatile LHRH or FSH and hCG therapy LHRH or FSH and hCG therapy

Hormonal substitution therapy in Hormonal substitution therapy in girls with hypogonadism girls with hypogonadism

When diagnosis of hypogonadism is firmly When diagnosis of hypogonadism is firmly established begin hormonal substitution established begin hormonal substitution therapy at 12-13ytherapy at 12-13y

Goal: to approximate normal adolescent Goal: to approximate normal adolescent development development

Initial therapy: ethinyl estradiol 5 ug by Initial therapy: ethinyl estradiol 5 ug by mouth or conjugated estrogen 0.3 mg (or mouth or conjugated estrogen 0.3 mg (or less) by mount daily for 4-6 mo. less) by mount daily for 4-6 mo.

After 6 mo of therapy begin cyclic therapy:After 6 mo of therapy begin cyclic therapy:Estrogen: first 21 d of monthEstrogen: first 21 d of monthProgestogen: 12Progestogen: 12thth to 21 to 21stst day of month day of month

puberty. definition of puberty it is the physiological stage that leads to reproductive capability...

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