Physiology of normal and abnormal puberty

1. Puberty
ABDULMAGID SARHAN
MD, FRCOG
ZAGAZIG UNIVERSITY

2. Puberty
❑ Definition of puberty
❑ Timing of puberty
❑ Hormonal changes
❑ Physical changes
❑ Abnormal puberty

3. Definition of Puberty
▪ Puberty is the process of physical changes through
which a child's body matures into an adult body
capable of sexual reproduction.
▪ Puberty is what happens in children's bodies that
changes them into adults.
▪ Puberty is the process of hormonal, physical and
psychological changes that make a child an adult
person.

4. Timing of Puberty
▪ The main factor is genetic
▪ Body weight
▪ Nutrition and general health
▪ Altitude
▪ Weather
▪ Light
▪ living standards , Rural and Urban areas

5. Timing of Puberty
There is a fairly good correlation between
▪ times of menarche of mothers and daughters and
between sisters.
▪ age of onset and duration of puberty; the earlier the
onset, the longer the duration

6. The Physiology of Puberty
❑ HORMONAL
I. Adrenarche
II. Decreasing repression of the gonadostat
III. Gonadarche
Gradual amplification of the GnRH-gonadotropin and
gonadotropin-ovarian steroid interactions leading to
gonadarche.
❑ PHYSICAL
I. Growth Spurt
II. Thelarche
III. Pubarche
IV. Menarche

7. The Physiology of Puberty
in the fetus,
neonate, infant, and
prepubertal child
are all capable of
secreting hormones
in adult
concentrations.

8. Adrenarche
▪ Occurs progressively in late childhood from about age
6-7 to adolescence (13-15 years of age).
▪ The clinical signs of adrenal androgen activity)
precedes by 2 years the linear growth spurt.
▪ Premature adrenarche by itself is occasionally seen.

9. Adrenarche
▪ Expressed by a rise in circulating androstenedione,
dehydroepiandrosterone (DHA),
dehydroepiandrosterone sulfate (DHAS).
▪ This is associated with an increase in size and
differentiation of the inner zone (zona reticularis) of the
cortex.
▪ The growth of pubic and axillary hair is due to an
increased production of adrenal androgens at puberty.

10. Decreasing repression of the gonadostat

11. Decreasing repression of the gonadostat
The Period of Infancy and Childhood
(the gonadostat) is highly sensitive to negative feedback
of estrogen (10 pg/mL). 6-15 times more sensitive to
negative feedback at this period than in the adult.

12. Alteration of GnRH-Gonadotropin and
Gonadotropin-Ovarian Steroid Interactions
❑ Augmented GnRH pulses first occurs during sleep. There is sleep-
associated release of LH in both sexes.
❑ This difference between nighttime and daytime switches by late
puberty with an increase in daytime and a decrease in sleep
pulsatility.
❑ GnRH pulses appear and are maintained independently of
steroid feedback.

13. Alteration of GnRH-Gonadotropin and
Gonadotropin-Ovarian Steroid Interactions
▪ GnRH acts as a self-primer on the gonadotrope cells by
inducing cell surface receptors specific for GnRH and
necessary for its action (up-regulation).
▪ FSH rises initially and plateaus in mid-puberty while LH
rises more slowly and reaches adult levels in late puberty.
▪ As gonadotropin secretion appears, ovarian steroid
synthesis is stimulated and estrogen secretion rises.

14. Stages of Pubertal Development
I. Growth Spurt.
II. Thelarche (breast development)
III. Pubarche (Pubic & Axillary hair)
IV. Menarche
4.5 Years (range 1.5 to 6).

15. Growth

16. Growth
▪ Occurs 2 years earlier (at 11-12 years)
than that of a boy
▪ in 1 year, her rate of growth doubles,
yielding a height increment of 6 - 11
cm .
▪ The average girl reaches this growth
peak about 2 years after breast
budding and 1 year prior to
menarche.

17. Growth
▪ due to:
o Estrogen
20 pg/mL
critical hormone in both sexes
o growth hormone (pulsatile fashion)
o insulin-like growth factor-I (IGF-I)
▪ Is influenced by growth in utero.
▪ Adrenal androgens are not involved.

18. Thelarche (breast development)

19. Breast Development

20. Pubarche

21. Menarche

22. Precocious Puberty

23. Precocious Puberty
▪ Pubertal changes before the age of 8 (menarche before age
10) are regarded as precocious. (the mean ±2.5 SD)
▪ substantial number of normal girls begin pubertal
development before age 8.67 .
▪ In children ages 6 to 8, the clinician's response is influenced by
the anxiety and distress in patient and parents, and the
clinical presentation.

24. Precocious Puberty
▪ GnRH-Dependent
(True, GnRH-Dependent, central)
▪ Idiopathic 74.0% 41.0%
▪ CNS problem 7.0% 26.0%
▪ GnRH-Independent
(Precocious Pseudo puberty, GnRH-independent, peripheral)
▪ Ovarian (cyst or tumor) 11.0%
▪ Testicular (cyst or tumor) 10.0%
▪ McCune-Albright syndrome 5.0% 1.0%
▪ Adrenal feminizing 1.0% 0.0%
▪ Adrenal masculinizing 1.0% 22.0%
▪ Ectopic gonadotropin production 0.5% 0.5%

25. Precocious Puberty
▪ In clinical practice, these classifications are of little practical
use because they are final diagnoses after a comprehensive
evaluation.
▪ Precocity occurs in girls 5 times more frequently than in boys,
and almost three-quarters of precocity in girls is idiopathic.
▪ The clinician is obligated to rule out a serious disease process in
central or peripheral sites.
▪ In girls over 4 years old a specific etiology is rarely found. In
younger girls, a CNS lesion is usually present.

26. Precocious Puberty
❑ Premature Thelarche (breast budding without pubertal growth)
❑ Often occurs in the first few years of life and is usually self-limited,
requiring no therapy.
❑ Follow-up has revealed that most of these children experience normal
puberty and growth and, eventually, normal reproduction.
❑ The breast growth may regress after a few months, wax and wane for
years, or last until puberty.
❑ Premature thelarche can be unilateral. Premature thelarche later in
childhood is a component of precocious puberty and warrants

27. Precocious Puberty
Premature Menarche
❑ Isolated premature menarche without other evidence of maturation is an
exceedingly rare presentation of precocity.
❑ Normal growth, development, and fertility are not affected.
❑ Should consider:
❑ infection,
❑ the presence of a foreign body,
❑ abuse and trauma, and
❑ local neoplasms.

28. Precocious Puberty
Premature Adrenarche
▪ The appearance of pubic hair before age 6 in black girls and
age 7 in white girls,
▪ An adrenal enzyme deficit should be excluded by appropriate
laboratory testing
▪ Treatment is not necessary because the transient acceleration
in growth and bone maturation has no major influence on
puberty or final height.
▪ Surveillance of these patients should be continued because,
although not certain, it has been suggested that they have an
increased incidence of anovulation, hirsutism, and
hyperinsulinemia.

29. Diagnosis of Precocious Puberty
The cause of precocious development may be obvious by
findings in the history or physical examination. Familial
occurrence helps to exclude certain disease processes (tumors).
Clinically, the nature of precocity dictates certain diagnostic
priorities.
✓ Rule out life-threatening disease. e.g. neoplasms of the CNS,
ovary, and adrenal.
✓ Define the velocity of the process. Is it progressing or
stabilized?.
✓ Exclude isolated, nonendocrine causes of vaginal bleeding
e.g. trauma, foreign body, vaginitis, genital neoplasm.

30. Diagnosis of Precocious Puberty
Physical Diagnosis:
• Record of growth, Tanner stages, height and weight percentiles.
• External genitalia changes.
• Abdominal, pelvic, neurologic examinations.
• Signs of androgenization.
• Special findings: McCune-Albright, hypothyroidism.
Laboratory Diagnosis:
• Bone age.
• Head MRI, ultrasonography of abdomen and pelvis.
• FSH, LH, hCG assays.
• Thyroid function tests (TSH and free T4).
• Steroids (serum DHAS, T, E, P, 17-hydroxy P).
• Inhibin levels.
• GnRH testing.

31. Diagnosis of Precocious Puberty
Laboratory Findings in Disorders Producing Precocious Puberty
Gonadal Size Basal FSH/LH Estradiol GnRH
Idiopathic Increased Increased Increased Pubertal
Cerebral Increased Increased Increased Pubertal
Gonadal Unilat. incr. Decreased Increased Flat
Albright Increased Decreased Increased Flat
Adrenal Small Decreased Increased Flat

32. McCune-Albright syndrome
(polyostotic fibrous dysplasia)
▪ Accounts for 5% of female precocity .
▪ Consists of:
▪ multiple disseminated cystic bone lesions that easily
fracture,
▪ cafee-au-lait skin spots of various sizes and shapes,
▪ sexual precocity.
▪ Can be associated with ovarian cysts, growth hormone-
and prolactin-secreting adenomas, hyperthyroidism,
adrenal hypercortisolism, and osteomalacia.

33. Treatment of Precocious Puberty
The objectives of management and treatment of precocious
puberty include:
✓ Diagnose and treat intracranial disease.
✓ Arrest maturation until normal pubertal age.
✓ Attenuate and diminish established precocious characteristics.
✓ Maximize eventual adult height.
✓ Facilitate the avoidance of abuse and reduction of emotional
problems, and provide contraception if necessary.

34. Treatment of Precocious Puberty
A number of therapies have been used to achieve these goals.
These have included:
✓ medroxyprogesterone acetate,
✓ cyproterone acetate, and
✓ danazol,
but in addition to undesirable side effects, bone maturation
and growth were not regularly or sufficiently controlled. These
drugs have been replaced by the use of
GnRH analogues.

35. Treatment of Precocious Puberty
GnRH analogues.
✓ The dose of GnRH agonist treatment is monitored by estradiol
levels. The objective is to maintain it less than 10 pg/mL
✓ Treatment is maintained until the epiphyses are fused or until
appropriate pubertal and chronologic ages are matched.
✓ Discontinuation of therapy is followed by prompt reactivation of
the pubertal process in a pattern similar to that of normal
adolescents.
✓ GnRH agonist treatment is not effective for noncentral forms of
precocious puberty.

36. Treatment of Precocious Puberty
psychosocial problems in children with precocious puberty.
✓ Intellectual, behavioral, and psychosexual maturation in keeping with
their chronological age, not their physical or pubertal age.
✓ Parents, teachers, and peers may have unrealistic expectations and
careful explanation must be given to parents.
✓ The children should be counseled that their secondary sexual
characteristics are normal albeit early.
✓ If the child is bright, advancement in school may be possible with special
tutoring and this can prove beneficial.
✓ Children with precocious puberty can place a stress on the marital or
family relationship, and psychological counseling can be useful.

37. Prognosis of Precocious Puberty
The prognosis for precocious puberty depends on the
underlying cause.
▪ adrenal hyperplasia
▪ ovarian tumors and adrenal tumors
▪ CNS causes

38. Prognosis of Precocious Puberty
▪ Short stature as an adult
▪ is approximately 152 cm .
▪ consider adding growth hormone to patients who
appear to be falling short of their predicted height,
however the expense of growth hormone is a factor .
▪ Most women have normal menstrual cycles and fertility,
and they do not have premature menopause.
▪ psychosexual scars.
▪ have higher verbal IQ scores.

39. ABDULMAGID SARHAN