Puberty Puberty By By

Dr. Khattab Omar Dr. Khattab Omar

Prof. & Head of Obstetrics and Prof. & Head of Obstetrics and Gynaecology Gynaecology

Faculty of Medicine, Al-Azhar Faculty of Medicine, Al-Azhar University, DamiettaUniversity, Damietta

Definition: Definition: It is the period of time during It is the period of time during

which 2ry sexual character-which 2ry sexual character-istics develop, menstruation istics develop, menstruation begins and the psychological begins and the psychological outlook changes. outlook changes.

It is the process by which sex-It is the process by which sex-ually immature persons be-ually immature persons be-come capable of reproduction. come capable of reproduction.

Pubertal changes include Pubertal changes include changes in body, mind and changes in body, mind and emotions. emotions.

The body changes occur in 5 stages:The body changes occur in 5 stages:

- breast growth, - breast growth, - pubic hair growth, - pubic hair growth, - axillary hair growth, - axillary hair growth, - growth spurt and - growth spurt and - menarche. - menarche.

Sequences of pubertal events: -The 1st steroid to increase is DHEA (at 6-8y). -Adrenarche(in DHEA, DHEAS & androstenedione) axillary (& pubic) hair growth with an increase in size & differentiation of the zona reticularis.

In hypergonadotrophic & hypo-gonadotrophic hypogonadism (e.g. gonadal dysgenesis & Kallmann’s syndrome) adrenarche occurs despite the absence of gonadarche. Adrenarche is not under control of Gn, ACTH or PRL. The stimulator appears to be a pituitary adrenal androgrn stimulat-ing factor (CASH, from the precursor pro-opio-melancortin [POMC]) which acts on ACTH-prepared & maintained adrenals.

Decreasing repression of the 'gonadostat’.

The proposed mechanism of ‘gonadostat’ is hypersensitivity to the -ve feedback of est-

rogen -- the important role in early childhood.

Gonadostat reaches a max at the age of 7.

Gradual amplification of the GnRH–Gn & Gn–steroid (the hypothalamo-pituitary-gonadal axis) interactions leading to 'gonadarche‘. FSH, then LH levels rise moderately before the age of 10. FSH rises initially, then plateaus in mid-puberty, while LH rises more slowly and reaches adult levels in late puberty). GnRH&LH pulses first increase during sleep Augmentation of pulsatile Gn secretion is the essential hormonal event of puberty.It is affected by endocrine, nutritional & psychological factors.

Gonadarche rise in estradiol level breast development, female fat distribution, as well as vulvar, vaginal and uterine growth.

- Also, growth hormone (Also, growth hormone (GHGH) ) secretion becomes secretion becomes critically dependent on the critically dependent on the gonadal estrogen secretiongonadal estrogen secretion

- GH levels increase before GH levels increase before the appearance of any sign the appearance of any sign of sexual development. of sexual development.

- It stimulates the produc-It stimulates the produc-tion of tion of IGF-IIGF-I. .

- Menarche occurs when - Menarche occurs when body weight is 42-52 kg body weight is 42-52 kg and 17% of this is fat. and 17% of this is fat.

- Ovulation: Regular - Ovulation: Regular ovulation occurs about ovulation occurs about 20 months after 20 months after menarche. menarche.

Hypothalamus

Ant. Pituit.

Gn secretion

FSH CASH & ACTH

GH

ovary

Adrenarche

in No. of growing follicles

Skeletal growth

in estrogen Growth of 2ry sexual organs in E2 first is irregular Irregular anovulatory menses then E2 rises steadily to a critical level LH secretion & ovulation + regular cycles

IGF-I

Timing and duration:Timing and duration:Reversal of central inhibition (by GnRH Reversal of central inhibition (by GnRH

– the important role in late child-– the important role in late child-hood) is due to a reduction in hood) is due to a reduction in melatonin secretion. melatonin secretion.

Puberty occurs at the age of 11.5 y Puberty occurs at the age of 11.5 y over a period of 2-5 y. over a period of 2-5 y.

There is a correlation between the age There is a correlation between the age of onset & duration of puberty; the of onset & duration of puberty; the earlier the onset, the longer the earlier the onset, the longer the duration. duration.

The major determinant of the timing The major determinant of the timing of puberty is genetic. of puberty is genetic.

Other factors appearing to influence Other factors appearing to influence the timing and the rate of progress-the timing and the rate of progress-ion of puberty are: geographic loca-ion of puberty are: geographic loca-tion, exposure to light, general tion, exposure to light, general health & nutrition, and psychologic health & nutrition, and psychologic factors. factors.

The principal factor responsible for The principal factor responsible for normal pubertal growth is insulin-like normal pubertal growth is insulin-like factor I (IGF -I), the mediator of sex factor I (IGF -I), the mediator of sex steroid induction of growth. steroid induction of growth.

Male : female skeletal mass Male : female skeletal mass or muscle mass = 1.5 or muscle mass = 1.5

Female : male body fat = 2. Female : male body fat = 2.

Breast development, pubic Breast development, pubic hair and axillary hair hair and axillary hair development constitute the development constitute the base of the Tanner system base of the Tanner system of classification. of classification.

Initial growth acceleration occurs first. Initial growth acceleration occurs first. Growth spurt occurs over a period of Growth spurt occurs over a period of about about 2 y2 y in an average rate of 8 cm/y. in an average rate of 8 cm/y.

Pubic hair develops over a period of Pubic hair develops over a period of about about 3 y3 y. .

Breast development completes over a Breast development completes over a period of about period of about 4 y4 y (between 9 & 12). (between 9 & 12).

Menarche occurs around the age of 12.6. Menarche occurs around the age of 12.6.

As a rule, pubic hair & breast develop-As a rule, pubic hair & breast develop-ment precede menarche by about 2 y. ment precede menarche by about 2 y.

Puberty (& growth spurt) starts in girls 2 Puberty (& growth spurt) starts in girls 2 y earlier than in boys. y earlier than in boys.

Tanner classification of female adolescent development.Tanner classification of female adolescent development.

Stage Stage Breast Breast Pubic hairPubic hair

I I Papillae elevated (pre-Papillae elevated (pre-adolescent), no breast buds. adolescent), no breast buds.

None None

II II Breast buds & papillae slightly Breast buds & papillae slightly elevated.elevated.

Sparse, long Sparse, long slightly pigmen.slightly pigmen.

III III Breasts and areolae confluent, Breasts and areolae confluent, elevated. elevated.

Dark, course, Dark, course, curly. curly.

IV IV Areolae and papillae project Areolae and papillae project above breast. above breast.

Adult-type, Adult-type, pubis onlypubis only

VVPapillae projected, mature. Papillae projected, mature. Lateral Lateral distribution. distribution.

Problems of puberty These include :

1- Acne, 2- Wrong shape, 3- PMS, 4- Dysmenorrhoea, 5- Precocious puberty and 6- Delayed puberty.

PRECOCIOUS PUBERTY Definition: It is development

of breast (or any 2ry sexual characteristic) before the age of 8 y, or menarche before the age of 10. Incidence: Precocity occurs in girls 5-x more frequently than boys.

Aetiology: 1- Most cases (90%) are constitutional (idiopathic; with Gn levels). In girls over the age of 4 years a specific aetiology is rarely found! A familial form does exist, but it is more common in boys.

2- CNS problems (7%) e.g. encephal-itis, meningitis & intracranial lesions. Hypothalamic hamartoma is the most common lesion in very young girls. An injury to the skull can stimulate precocity after a latent period of 1-2 months. The proposed mechanism is damage to the neural arm of the gonadostat. CNS neoplasms include optic gliomas and neurofibromas. Pineal tumours can be a cause only in male precocious puberty.

3- McCuneAlbright’s syndrome: 5%. Polyostotic fibrous dysplasia and café au lait patches.

Patients are usually younger than those of idiopathic precocity.

In most of the cases vaginal bleeding is the first sign.

4- Feminizing ovarian tumour ( Gn levels; 10%). It may be a functioning tumour or a benign one that induces the surrounding ovarian tissue to produce steroids

Differential diagnosis: Ovarian tumour precocious puberty Vs. follicular cyst precocious puber

Hepatoma and adrenal adenoma are extremely rare causes.

5- Adrenal hyperplasia or tumour virilizing prec. pub. (1%) or feminizing prec. pub. (1%).

6- Drugs like oestrogens.

The first 3 causes result in true prec pub (constitutional cases and CNS problems are GnRH-dependent, while Mc Cune Albright’s syndrome is GnRH-independent), ….. while the last 3 causes result in false precocious puberty (i.e. manifestations are reversible with removal of the cause. It may be partial or incomplete)

Presentation:Presentation: Increased growth is often the first change, Increased growth is often the first change, followed usually by thelarche and pubarche. followed usually by thelarche and pubarche.

McCune Albright syndromeMcCune Albright syndrome can be associated with can be associated with ovarian cysts, GH- and PRL-secreting adenomas, ovarian cysts, GH- and PRL-secreting adenomas, hyperthyroidism, hyperparathyroidism and Cushinghyperthyroidism, hyperparathyroidism and Cushing ’’s s disease. FSH & LH levels are low. Hepatitis, intestinal disease. FSH & LH levels are low. Hepatitis, intestinal polyposis and cardiac arrhythmias could occur. polyposis and cardiac arrhythmias could occur.

Premature thelarche:Premature thelarche: It most commonly occurs It most commonly occurs between 1 and 3 years of age. It may affect one or both between 1 and 3 years of age. It may affect one or both breasts. Somatic growth is not accelerated and bone breasts. Somatic growth is not accelerated and bone age isnage isn’’t advanced. t advanced.

Premature pubarche:Premature pubarche: It affects pubic &/or axillary hair. It affects pubic &/or axillary hair. It may be idiopathic. Children tend to be slightly taller It may be idiopathic. Children tend to be slightly taller with marginally advanced bone age and slightly with marginally advanced bone age and slightly elevated DHEA. Early cases may occur 2ry to androgen elevated DHEA. Early cases may occur 2ry to androgen excess (CAH or Leydig cell tumor). excess (CAH or Leydig cell tumor).

Premature menarche:Premature menarche: Surprisingly, E2 levels are in the Surprisingly, E2 levels are in the prepubertal range. Other causes of vaginal bleeding prepubertal range. Other causes of vaginal bleeding should be excluded. should be excluded.

Diagnostic priority:Diagnostic priority:

Exclude life-threatening Exclude life-threatening neoplasms of the CNS, neoplasms of the CNS, ovaries and adrenals.ovaries and adrenals.

Although most cases are Although most cases are idiopathic, this should be idiopathic, this should be a diagnosis by exclusion. a diagnosis by exclusion.

Work-up:Work-up:State age at onset, duration and progression. State age at onset, duration and progression.

Deduce family history & review body systems Deduce family history & review body systems

Examine skin for acne, adult-type body odor &cafExamine skin for acne, adult-type body odor &caféé au lait patches au lait patches

Assess maturation of breasts and genitalia.Assess maturation of breasts and genitalia.

Essential and basic is a left hand-wrist x-ray film. Essential and basic is a left hand-wrist x-ray film.

Head CT/MRI, abdominal & pelvic USSHead CT/MRI, abdominal & pelvic USS

FSH, LH & hCG assay FSH, LH & hCG assay

TFTs (TSH & free T4) TFTs (TSH & free T4)

DHAS, 17-OH-P, E2, testosterone & progesterone DHAS, 17-OH-P, E2, testosterone & progesterone

GnRH testing GnRH testing

Approach to diagnosis:Approach to diagnosis:

* Full signs of prec pub + pubertal levels of Gn (basal * Full signs of prec pub + pubertal levels of Gn (basal & Gn RH stimulated) = ? pituitary source of Gn. & Gn RH stimulated) = ? pituitary source of Gn.

* If Gn levels are suppressed by GnRH while E* If Gn levels are suppressed by GnRH while E22 levels levels are markedly increased, = ? ectopic source of Gn. are markedly increased, = ? ectopic source of Gn.

* Signs of sexual puberty + skeletal maturation = ? * Signs of sexual puberty + skeletal maturation = ? ovarian tumour or cyst (high E2 level & low Gn). ovarian tumour or cyst (high E2 level & low Gn).

NB: If progesterone level is high = ? Luteoma. NB: If progesterone level is high = ? Luteoma.

* Signs of sexual puberty+ virilization=adrenal hyper-* Signs of sexual puberty+ virilization=adrenal hyper-plasia (plasia (17 OH-P or DOC) or virilizing adrenal or 17 OH-P or DOC) or virilizing adrenal or ovarian tumour (ovarian tumour ( DHEA-S or androstenedione). DHEA-S or androstenedione).

* Signs of sexual puberty + vaginal bleeding + short * Signs of sexual puberty + vaginal bleeding + short stature with DELAYED bone age = hypothyroidism. stature with DELAYED bone age = hypothyroidism.

TreatmentTreatment Prompt investigation and treatment are essential Prompt investigation and treatment are essential

to avoid short stature. to avoid short stature. Causal treatment for tumours and hyperplasia. Causal treatment for tumours and hyperplasia.

Cyproterone acetate, medroxyprogesterone Cyproterone acetate, medroxyprogesterone acetate or testolactone (an aromatase inhibitor). acetate or testolactone (an aromatase inhibitor).

GnRHa for true precocious puberty (idiopathic & GnRHa for true precocious puberty (idiopathic & neurologic) is the treatment of choice because it neurologic) is the treatment of choice because it delays both somatic and skeletal maturation. delays both somatic and skeletal maturation. Treatment is continued until the age of 11.5-12 Treatment is continued until the age of 11.5-12 GnRHa therapy fails with McCune Albright synd GnRHa therapy fails with McCune Albright synd and has little effect beyond Tanner stage 3. and has little effect beyond Tanner stage 3.

NB:NB: Precocious puberty is not associated with Precocious puberty is not associated with premature menopause.premature menopause.

DELAYED PUBERTY DELAYED PUBERTY

= No signs of puberty by the = No signs of puberty by the age of 14; no thelarche by the age of 14; no thelarche by the age of 13; no menarche by the age of 13; no menarche by the age of 15. age of 15.

Management should not be Management should not be postponed waiting for delayed postponed waiting for delayed menarche.menarche.

Aetiology:Hypergonadotrophic hypogonadism is the most frequent cause of delayed puberty (43%): Gn, steroids. Ovarian failure:- with abnormal karyotype = 26%. - with normal karyotype constitutes 17% (46,XX = 15%; 46,XY = 2%). Examples: Mumps, resistant ovary syndrome (absent follicular receptors for Gn) & autosomal recessive familial form.

Hypogonadotrophic hypogonadismHypogonadotrophic hypogonadism = 31%. This may be: = 31%. This may be: Reversible (18%): Reversible (18%): Physiologic delay = 10%. GnRH challenge test differ-Physiologic delay = 10%. GnRH challenge test differ-

entiates constitutional delay from similar conditions. entiates constitutional delay from similar conditions. Weight loss/anorexia = 3%. Weight loss/anorexia = 3%. Prolactinomas = 1.5%. Prolactinomas = 1.5%. Primary hypothyroidism = 1%. Primary hypothyroidism = 1%. CAH = 1%. CAH = 1%. CushingCushing’’s disease = 0.5%. s disease = 0.5%. Irreversible (13%): Irreversible (13%): GnRH deficiency = 7%. GnRH deficiency = 7%. Hypopituitarism = 2%. Hypopituitarism = 2%. Craniopharyngeoma, in late childhood, is the most Craniopharyngeoma, in late childhood, is the most

common neoplasm associated with delayed puberty = common neoplasm associated with delayed puberty = 1%. 1%.

Congenital CNS defects = 0.5%.Congenital CNS defects = 0.5%. Other pituitary adenomas = 0.5%.Other pituitary adenomas = 0.5%. Malignant pituitary tumours = 0.5%.Malignant pituitary tumours = 0.5%.

Eugonadotrophic hypogonadismEugonadotrophic hypogonadism = 26%.= 26%. Delayed menarche with adequate Delayed menarche with adequate

2ry sexual characters. 2ry sexual characters. Mullerian agenesis = 14%. Mullerian agenesis = 14%. Inappropriate feedback leading to Inappropriate feedback leading to

anovulation & androgen excess (→ anovulation & androgen excess (→ oestrogen excess) = 7%. oestrogen excess) = 7%.

Vaginal septum = 3%. Vaginal septum = 3%. Androgen insensitivity syndrome = 1%. Androgen insensitivity syndrome = 1%. Imperforate hymen = 0.5%. Imperforate hymen = 0.5%. Hand-Schuller-Christian disease Hand-Schuller-Christian disease

(histiocytosis-X) in children is associated (histiocytosis-X) in children is associated with delayed growth & puberty. with delayed growth & puberty.

Loss of 10-15% of weight for height Loss of 10-15% of weight for height delayed puberty and/or menarche. delayed puberty and/or menarche.

The commonest cause of The commonest cause of delayed puberty is delayed puberty is ovarian failure. ovarian failure.

More than 1/4 of the girls More than 1/4 of the girls with delayed puberty with delayed puberty have chromosomal have chromosomal abnormalities. abnormalities.

ManagementManagement Serum Serum GnGn assay is important in distinguishing assay is important in distinguishing

hypo- & hyper-gonadtrophic causes of delayed hypo- & hyper-gonadtrophic causes of delayed puberty. puberty.

With With low FSHlow FSH levels, levels, skull films & prolactinskull films & prolactin assay assay are mandatory. are mandatory.

Absent 2ry sexual characters: Conjugated estro-Absent 2ry sexual characters: Conjugated estro-gen 1.5 mg twice daily until breast develop-gen 1.5 mg twice daily until breast develop-ment is progressing or spotting occurs. ment is progressing or spotting occurs.

Dose is then reduced to OD, with progestin (10 Dose is then reduced to OD, with progestin (10 mg provera) is added for 10 days/month.mg provera) is added for 10 days/month.

Therapy is discontinued when the bone age Therapy is discontinued when the bone age matches the chronologic age. matches the chronologic age.

Patients with inappropriate feedback should Patients with inappropriate feedback should receive progestins every other month to receive progestins every other month to prevent endometrial hyperplasia. prevent endometrial hyperplasia.

ThankThank you you