Puberty And Its Problems

كلية الطب ?جامعة بابل المرحلة الخامسة
د-نسرين مالك
Gynaecology

Puberty And Its Problems

Puberty is define as the period of time during which secondary sexual characteristics develop, menstruation begins, and the psychological outlook of the girl changes, as she develops a more adult aspect to herself.
The end result of puberty is the establishment of the fully physically mature adult woman, capable of reproductive performance, and fully psychologically developed as an adult.

The onset of puberty depends on several factors :-

1-Genetic factors.
2-Geographical factors:- peoples of high altitudes usually have a delay in their onset of puberty.
3- Nutritional factors :-As the body fat is intimately involved in the coordination of the onset of GnRH release.
4- Heavy exercises : Menarche is often delayed in gymnasts, distance runners, and ballet dancers, as some theories propose that this due to an insufficient percentage of body fat that may result in hypothalamic anovulation and amenorrhea.
5-Psychological factors: Like anorexia nervosa which lead to decrease in body fat ,so affect the release of GnRH from the hypothalamus.

The endocrinological changes :-
1-The hypothalamo-pituitary-ovarian axis is functionally complete during the later half of fetal life . The follicle stimulating hormone (FSH) levels are suppressed from 20 weeks of gestation by the production of oestrogen by the placenta and by the fetus itself.

2- At birth the fetus is separated from its placenta and therefore the major source of oestrogen is removed. The FSH level then rises in response to hypo-oestrogenic state of the fetus and remains elevated for some 6-18 months after birth .
After this time is suppressed due to the central inhibition of the production of the gonadotrophin –releasing hormone (GnRH )which controls the pituitary production of FSH ( this is controlled by a gene in the GnRH cell nucleus in the hypothalamus under the effect of leptin , a peptide produced by the fat cells).

3- During the childhood ,FSH pulses are almost undetectable , and at around the age of 8 or 9 years a change gradually occurs in the function of the GnRH cell.
This change begins with production of single nocturnal spikes of GnRH and subsequently FSH. These spikes of FSH increase in frequency during the night- time hours over a period of 1-2 years. Eventually ,the frequency of the FSH pulses increases such that they are detectable in the daylight hours ,and after a period of 4-5 years ,a fully functional production of GnRH with normal adult frequency and pulse amplitude leads to the establishment of the ovulatory menstrual cycle. Puberty therefore occurs over a total of 5-10 years .

Physiology of puberty :-

The physical changes of puberty are divided into five stages in the following sequences :-
1-Thelarche :The onset of breast development , usually begins between 9 and 11 years of age .It is a sign of ovarian estrogen production , and it is completed over approximately 3 years.

2-Pubic hair growth.
3-Axillary hair growth.
Adrenarche refers to the production of androgen from the adrenal gland ,which is
important for the growth of pubic and axillary hair ( pubarche ).This is start in 11-12
years of age .

4-Growth spurt :-The growth spurt in children occurs about 2 years earlier in girls than boys , and in most girls in UK occurs around the age of 11.5- 12 years .
Growth velocity at this stage reaches a peak of 8 cm per year , but the production of oestrogen from the ovary at this time eventually closes the epiphyses such that final height is achieved at around the age of 14.5 years.

5-Menarche :- The average age at onset of menstruation is between 12-13 years, or 2.5 years after the development of the breast buds.
The adolescent menstrual cycle is usually irregular for the first 1 to 2 years after menarche , reflecting anovulatory cycles . On average, it takes about 2 years after menarche before regular ovulatory cycles are achieved ( it may take some 5-8 years before the menstrual cycle normality is established ).


The breast , pubic and axillary hair development are classified by the Tanner system into five stages:

Tanner stages of development of secondary sexual characteristics:-

Breast development:-
Stage 1: Prepubertal.
Stage 2: Breast bud stage with elevation of breast and papilla; enlargement of areola.
Stage 3: Further enlargement of breast and areola; no separation of their contour.
Stage 4: Areola and papilla form a secondary mound above level of breast.
Stage 5: Mature stage: projection of papilla only, related to recession of areola.

Pubic hair:-
Stage 1: Prepubertal (can see velus hair similar to abdominal wall).
Stage 2: Sparse growth of long, slightly pigmented hair, straight or curled, along labia.
Stage 3: Darker, coarser and more curled hair, spreading sparsely over junction of pubes.
Stage 4: Hair adult in type, but covering smaller area than in adult; no spread to medial
surface of thighs.
Stage 5: Adult in type and quantity, spread to medial surface of thighs with horizontal distribution ("feminine").


Common pubertal problems:-

Precocious puberty:-
Is the development of any sign of secondary sexual characteristics at an age earlier ,2.5 SD below suspected age of maturation ( before 8 years of age ).
Most cases of precocious puberty are idiopathic (75? ).

The problem of such condition is that early maturation will cause early epiphyseal closure causing half of the cases to be less than 150 cm long , other effect is contracted pelvis. So early examination, diagnosis of every suspected cases is important to eliminate serious disease and arrest premature osseous closure.

Classification of precocious puberty:-
Precocious puberty classified according to the secondary sexual characteristics to :-
1- Heterosexual precocious puberty:- in which there is development of secondary sexual characteristics opposite from the anticipated phenotypic sex, due to increase androgen secretion, like virilizing neoplasm ( ovarian or adrenal ), congenital adrenal hyperplasia , exogenous androgen exposure .



2- Isosexual precocious puberty:- development of secondary sexual characteristics
that go with anticipated phenotypic sex.

Isosexual precocious puberty divided into :-
A-True isosexual precocious puberty ( central precocious puberty ):-
In this type the hypothalamus start to work, the causes are :
1- Idiopathic 90? ( no brain cause ).
2- Organic brain damage 10? (as following meningitis or hydrocephaly ).

B-Pseudoisosexual precocious puberty ( Peripheral precocious puberty ):-
Here the ovary work automatically (independent on hypothalamus) so the estrogen source either from the ovaries or from a source outside the ovaries examples ;
1- Malignant ovarian tumours that secreting estrogen like granulosa cell tumours,Brenner tumours and others.
2- Adrenal tumor which is androgenic type and rarely estrogenic one.
3- Exogenous estrogen exposure like combined contraception hormones ,or steroids
for medical use.
4-Chronic severe hypothyroidism, this will stimulate the pituitary gland to secrete
TSH , so excessive TSH will cross react with FSH and LH independent on
GnRH.
5-McCune- Albright syndrome :- which is a disorder involving cystic bony change (polyostotic fibrous dysplasia), there is also associated endocrine dysfunction particularly of the hypothalamus and pituitary gland, therefore precocious puberty is common in this condition .
6-Peutz-jeggers syndrome:- is characterized by bleeding per rectum , pigmentation in the lips; this syndrome makes the ovary more susceptible to tumor.

Precocious puberty either incomplete or complete according to the degree of changes that occur.
Incomplete precocious puberty:- This is termed incomplete because somatic changes do not occur in sequence and it only involves the breast and pubic hair.
Complete precocious puberty :- In which the whole physical changes occur completely and in their normal sequences.
The beginning of incomplete precocious puberty may be the beginning of complete one, so we must examine the patient after 3 months to ensure if this is a transient one or not.

Diagnosis of precocious puberty:-
The diagnosis made by taking history ,physical examination ,and investigation;
1- History ; Family history of premature pubertal development should be excluded,
sequence and velocity of sexual maturation , drugs and hormones
exposure , CNS infection, tumors, seizure , and bleeding per rectum.

2- Physical examination; 1- Appearance of pigmentations.
2- Skeletal deformities, serial height? weight recordings.
3- Secondary sexual characteristics and staging.
4-Breast examination.
5-Careful abdominal and pelvic examination.
6- Full neurological examination .
7-Visual field testing.

3- Investigations: Radiological;1- Skull x- ray(for pituitary gland ) .
2-CT scan for sella turcica.
3- U\S for abdomen and pelvis.
4- MRI for brain, abdomen(adrenal) and pelvis.
5- Serial bone age.

Laboratory; 1- FSH, LH, hCG (the hCG hormone it has been found to be secreted by some ovarian germ cell tumours).
2- Dehydroepiandrosterone sulfate (DHEAS).
androstendione, testosterone , esradiol.
3- Progesterone, 17-OH progesterone,11- deoxycortisol.
For diagnosis of congenital adrenal hyperplasia.
4- Thyroid function test (TSH, free T4 or freeT4 Index).
5- GnRH analogue test.
6- EEG (Electoencephalography).

Treatment:-
Most female has idiopathic precocious puberty (75?) ,these girls requires treatment to prevent further sex steroid release and accelerated epiphyseal fusion.

1-The most effective treatment is by GnRH agonists. they are available as long acting formulations administered as intramuscular injection ,subcutaneous injection, and also available as intranasal sprays. such as nafarelin (200 mcg intranasal spray) or leuprolide acetate depot (3.75 mg intramuscularly ).

Long term GnRH agonist treatment will suppress pituitary release of LH and FSH, resulting in decline of gonadotrophin level to prepubertal concentration and arrest gonadal steroid secretion .

The child can remain on this therapy until aged about 11.5-12 years, after that normal gonadotrophin release , sex steroid production ,and pubertal maturation will reassume following discontinuation of GnRH agonist therapy .
GnRH agonist not indicated in precocious puberty that is independent on gonadotrophin release (estrogen secreting neoplasm ), unless the hypothalamic- pituitary axis has been activated.

2-Other type of treatment is medroxyprogesterone acetate (MPA) as an oral or intramuscular rout.
MPA is effective in retarding breast and genital development ,but has no effect on peak height or osseous maturation.

3-Individuals with tumors, infections or other CNS disorders requires neurosurgical consultation .

4-Individuals with pseudoprecocious puberty treatment is done by identifying the cause and treated accordingly such as elimination of exposure to exogenous compounds, and those with abdominal, pelvic or adrenal neoplasm require surgical exploration.

Delayed puberty:- Delayed puberty is characterized by the absence of breast development by the age of 14 years or the absence of menses by age of 16 years .

Categories:-
1- Hypergonadotrophic hypogonadism : It includes conditions in which ovaries or gonads are not functioning and are unable to respond to gonadotrophins (FSH, LH) and this result in the gonadotrophins levels will be high. Examples include Turner syndrome (45X0); gonadal dysgenesis; idiopathic premature ovarian failure ; autoimmune ovarian failure; and ovarian failure secondary to radiotherapy or chemotherapy.

2-Hypogonadotrophic hypogonadism: The ovaries are normal; however, the signal from hypothalamus is absent. Examples are includes Kallmann syndrome ( isolated GnRH deficiency), or hypothalamic suppression by stress, severe disease or malnutrition, or tumor invasion of the pituitary (prolactinoma or craniopharyngioma).

3-Eugonadotrophic: Constitutional delay .These patients have normal progression of the stages of puberty; the initiation of the process is simply delayed.

Management:-
Treatment depends on the etiology of the delay. In cases of gonadal dysgenesis ,the gonads should be removed at diagnosis because of the risk of neoplastic degeneration. Otherwise hormone replacement with estrogen , and subsequently both estrogen and progesterone ( the introduction of progesterone to the regime usually occurs 18 months to 2 years after initial estrogen ), the hormonal replacement is required to promote sexual development and menarche.
In case of isolated GnRH deficiency but there is functioning pituitary gland can give GnRH agonist, or give gonadotrophins (FSH and LH), while in case of damaged pituitary gland the GnRH agonist will be ineffective so we can give gonadotrophins (FSH and LH) in order to stimulate the ovaries.