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Benha University Hospital, Egypt 
Email: elnashar53@hotmail.com 
Aboubakr Elnashar
Define 
Transitional stage from childhood to adulthood manifested by physiological changes & development of SSC . 
Aboubakr Elnashar
Timing Usually occurs between the ages of 10 & 16 years . 
Major determination is genetic. Other factor . 
1.Geographic location 
2. Exposure to light. 
3.General health & nutrition: 
Aboubakr Elnashar
A.Critical body weight of 47.8 Kg (Frisch hypothesis). 
B.A greater percentage of body fat (16% to 23.5%) may serve as initiating signal. Moderately obese girls have earlier menarche. Anorectics have delayed menarche. Puberty is delayed in morbid obesity, other factors are involved. 
Aboubakr Elnashar
What 
When 
How 
1. Thelarche 
Development of breast, 5Taner stages 
±10 yrs, first sign of puberty 
E2 
2. Adrenarche 
Development of pubic hair, 5 Taner stages & axillary hair, 3Taner stages 
PH: 1yr after Thelarche 
AH is the final SCC 
Adrenal androgen 
3. Spurt of growth 
Accelerated growth, 6-11cm/yr 
With adrenarche 
GH & E2 
4. Menarche 
The first menstruation 
±12yr 
(9-17.7) 
Midpubertal E2 
Stages (Physiological changes) 
The pubertal sequence requires 4.5 yrs. (range, 1.5-6 yrs) 
Aboubakr Elnashar
Aboubakr Elnashar
Aboubakr Elnashar
5. Deposition of SC fat: 17% to menstruate & 22% to ovulate 6. Genital organs changes: Mons pubes, labia maiora & minora: increase in size. Vagina: .length: increase, appearance of the rugae .Epithelium: thick, stratified squamous., containing glycogen .pH: acidic. 
Aboubakr Elnashar
Aboubakr Elnashar
Uterus: enlarge, U/C:2/1 Ovaries: .increase in size, almond shape .300 thousands primary follicle at menarche (2 million at birth) 
Aboubakr Elnashar
Summary of pubertal events 1.FSH & LH rise moderately before the age of 10 yrs, followed by a rise in E2. LH pulse frequency increases are first seen in sleep but then are extended throughout the day. The final adult pattern is 1.5 to 2 hrs intervals between pulse. 2.Increased levels of E2 (gonadarche) results in Maturation of SSC. Increased skeletal growth at low levels of E2. Increased GH & IGF-1 
Aboubakr Elnashar
Aboubakr Elnashar
3. Adrenal androgen cause adrenarche (pelvic & axillary hair). No major role in growth. It is an independent event. 
4. Midpuberty levels of E2 are sufficient to induce menstruation. 
5. Postmenarchal periods are irregular for 12-18 mo {LH surge is late pubertal event} 
Aboubakr Elnashar
Aboubakr Elnashar
Leptin & puberty 
Leptin is a peptide secreted by adipose tissues; it acts on CNS neurons, regulating eating behavior & energy balance. 
Higher levels of leptin correspond to earlier menarche. Girls with idiopathic precocious puberty have higher leptin levels. Leptin levels decrease with increasing Tanner stage. They have increased sensitivity to leptin. The decrease may allow greater food intake. 
Aboubakr Elnashar
Growth hormone: 
At puberty its secretion is critically dependent on sex steroid. 
It stimulates IGF-1 in cartilage & IGF-1 production in liver. 
Aboubakr Elnashar
Define Breast development <8 y or menstruation <9 y. 
Aboubakr Elnashar
Etiology, Classification 
A. True, GnRH dependent, complete, central, isosexual: Activation of the HPO axis, development of the gonads, SSC & ovulation 
1.Constitutional, idiopathic: (85%)diagnosed by exclusion. 
2.CNS: Meningitis, encephalitis, hydrocephalus 
Aboubakr Elnashar
B. Pseudo, GnRH independent, incomplete, peripheral, iso or hetrosexual : 
No activation of the HPO axis, but extrapituitary HCG or sex steroid exposure. 
No developments of the gonads, No ovulation but development of SSC. 
Aboubakr Elnashar
1. Isosexual: 
Feminizing T (Granulosa-Theca cell, malignant teratoma). 
Estrogen intake. 
Albright S (precocious puberty, café-au-lait skin patches, cystic bony changes). 
Hypothyroidism (Short stature & retarded bone age). 
Aboubakr Elnashar
The small cyst like space is similar to the Call-Exner bodies normally seen in granulosa cells 
Aboubakr Elnashar
Aboubakr Elnashar
2. Hetrosexual: Virilizing T: virilization but no uterine bleeding. Androgen intake. CAH 
Aboubakr Elnashar
C. Partial: premature thelarche or adrenarche. It is due to end-organ increased sensitivity to normal circulating low E or A. Follow-up 
Aboubakr Elnashar
Diagnosis 
History 
Examination 
i. Growth: Tanner stage, height & weight percentile 
ii. External genitalia changes 
iii. Abdominal, pelvic & neurological examination. 
IV. Signs of androgenization 
v. Other findings: signs of Albright S, hypothyroidism 
Aboubakr Elnashar
d. X ray of the lower ends of radius & ulna:bone age 
a. Retarded: hypothyroidism b. Normal: Partial 
c. Advanced: 
FSH: Low (<2 IU/ml) ---- pseudo-----follow up 
Normal (> 2 mIU/ml) ----- true: 
CT or MRI --------Normal (idiopathic) 
Abnormal (CNS lesion) 
Aboubakr Elnashar
Treatment Objectives: 
•Arrest maturation until normal pubertal age. 
•Attenuate & diminish established precocious characteristics. 
•Maximize adult height. 
•Avoid abuse, reduce emotional & social problems 
Aboubakr Elnashar
Treatment of the cause: 
•Albright S ( MPA or Testolactone, aromatase inhibitor). 
•Ovarian or CNS tumor (excision). 
•Hypothyriodism, CAH 
Aboubakr Elnashar
Constitutional: GnRh analogue Drug of choice because it achieves all objectives. It acts by binding to the anterior pituitary receptors causing down-regulation & desensitization of the pituitary. 
Aboubakr Elnashar
Regression of symptoms occurs in the first year {Regression of pubertal characteristics, amenorrhea & decreased growth velocity}. Delayed epiphyseal fusion; treatment more effective if begun before bone age >12 yrs. 
Aboubakr Elnashar
Maintain E2 at <10 pg/mL. 
Children require higher doses than adults for suppression. 
Adrenarche will continue. 
Treatment is continued until the epiphyses are fused or the appropriate pubertal & chronological ages are matched. 
Aboubakr Elnashar
SSC do not develop by the age of 14 y or no menstruation till age of 16y 
Aboubakr Elnashar
It is either : 
* Delayed onset: Breast bud does not appear till 13 years or menarche does not occur till 16 years . or 
* Delayed progreession : Menarche does not occur within 5 years after breast bud . 
Aboubakr Elnashar
Causes Early cycles are anovulatory E unopposed by P endometrial hyperplasia Treatment for 3 cycles: Norethistrone acetate 5mg twice daily for 21 d or OCP 
Aboubakr Elnashar
Benha University Hospital, Egypt 
E-mail:elnashar@hotmail.com 
Aboubakr Elnashar

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Puberty

  • 1. Benha University Hospital, Egypt Email: elnashar53@hotmail.com Aboubakr Elnashar
  • 2. Define Transitional stage from childhood to adulthood manifested by physiological changes & development of SSC . Aboubakr Elnashar
  • 3. Timing Usually occurs between the ages of 10 & 16 years . Major determination is genetic. Other factor . 1.Geographic location 2. Exposure to light. 3.General health & nutrition: Aboubakr Elnashar
  • 4. A.Critical body weight of 47.8 Kg (Frisch hypothesis). B.A greater percentage of body fat (16% to 23.5%) may serve as initiating signal. Moderately obese girls have earlier menarche. Anorectics have delayed menarche. Puberty is delayed in morbid obesity, other factors are involved. Aboubakr Elnashar
  • 5. What When How 1. Thelarche Development of breast, 5Taner stages ±10 yrs, first sign of puberty E2 2. Adrenarche Development of pubic hair, 5 Taner stages & axillary hair, 3Taner stages PH: 1yr after Thelarche AH is the final SCC Adrenal androgen 3. Spurt of growth Accelerated growth, 6-11cm/yr With adrenarche GH & E2 4. Menarche The first menstruation ±12yr (9-17.7) Midpubertal E2 Stages (Physiological changes) The pubertal sequence requires 4.5 yrs. (range, 1.5-6 yrs) Aboubakr Elnashar
  • 8. 5. Deposition of SC fat: 17% to menstruate & 22% to ovulate 6. Genital organs changes: Mons pubes, labia maiora & minora: increase in size. Vagina: .length: increase, appearance of the rugae .Epithelium: thick, stratified squamous., containing glycogen .pH: acidic. Aboubakr Elnashar
  • 10. Uterus: enlarge, U/C:2/1 Ovaries: .increase in size, almond shape .300 thousands primary follicle at menarche (2 million at birth) Aboubakr Elnashar
  • 11. Summary of pubertal events 1.FSH & LH rise moderately before the age of 10 yrs, followed by a rise in E2. LH pulse frequency increases are first seen in sleep but then are extended throughout the day. The final adult pattern is 1.5 to 2 hrs intervals between pulse. 2.Increased levels of E2 (gonadarche) results in Maturation of SSC. Increased skeletal growth at low levels of E2. Increased GH & IGF-1 Aboubakr Elnashar
  • 13. 3. Adrenal androgen cause adrenarche (pelvic & axillary hair). No major role in growth. It is an independent event. 4. Midpuberty levels of E2 are sufficient to induce menstruation. 5. Postmenarchal periods are irregular for 12-18 mo {LH surge is late pubertal event} Aboubakr Elnashar
  • 15. Leptin & puberty Leptin is a peptide secreted by adipose tissues; it acts on CNS neurons, regulating eating behavior & energy balance. Higher levels of leptin correspond to earlier menarche. Girls with idiopathic precocious puberty have higher leptin levels. Leptin levels decrease with increasing Tanner stage. They have increased sensitivity to leptin. The decrease may allow greater food intake. Aboubakr Elnashar
  • 16. Growth hormone: At puberty its secretion is critically dependent on sex steroid. It stimulates IGF-1 in cartilage & IGF-1 production in liver. Aboubakr Elnashar
  • 17. Define Breast development <8 y or menstruation <9 y. Aboubakr Elnashar
  • 18. Etiology, Classification A. True, GnRH dependent, complete, central, isosexual: Activation of the HPO axis, development of the gonads, SSC & ovulation 1.Constitutional, idiopathic: (85%)diagnosed by exclusion. 2.CNS: Meningitis, encephalitis, hydrocephalus Aboubakr Elnashar
  • 19. B. Pseudo, GnRH independent, incomplete, peripheral, iso or hetrosexual : No activation of the HPO axis, but extrapituitary HCG or sex steroid exposure. No developments of the gonads, No ovulation but development of SSC. Aboubakr Elnashar
  • 20. 1. Isosexual: Feminizing T (Granulosa-Theca cell, malignant teratoma). Estrogen intake. Albright S (precocious puberty, café-au-lait skin patches, cystic bony changes). Hypothyroidism (Short stature & retarded bone age). Aboubakr Elnashar
  • 21. The small cyst like space is similar to the Call-Exner bodies normally seen in granulosa cells Aboubakr Elnashar
  • 23. 2. Hetrosexual: Virilizing T: virilization but no uterine bleeding. Androgen intake. CAH Aboubakr Elnashar
  • 24. C. Partial: premature thelarche or adrenarche. It is due to end-organ increased sensitivity to normal circulating low E or A. Follow-up Aboubakr Elnashar
  • 25. Diagnosis History Examination i. Growth: Tanner stage, height & weight percentile ii. External genitalia changes iii. Abdominal, pelvic & neurological examination. IV. Signs of androgenization v. Other findings: signs of Albright S, hypothyroidism Aboubakr Elnashar
  • 26. d. X ray of the lower ends of radius & ulna:bone age a. Retarded: hypothyroidism b. Normal: Partial c. Advanced: FSH: Low (<2 IU/ml) ---- pseudo-----follow up Normal (> 2 mIU/ml) ----- true: CT or MRI --------Normal (idiopathic) Abnormal (CNS lesion) Aboubakr Elnashar
  • 27. Treatment Objectives: •Arrest maturation until normal pubertal age. •Attenuate & diminish established precocious characteristics. •Maximize adult height. •Avoid abuse, reduce emotional & social problems Aboubakr Elnashar
  • 28. Treatment of the cause: •Albright S ( MPA or Testolactone, aromatase inhibitor). •Ovarian or CNS tumor (excision). •Hypothyriodism, CAH Aboubakr Elnashar
  • 29. Constitutional: GnRh analogue Drug of choice because it achieves all objectives. It acts by binding to the anterior pituitary receptors causing down-regulation & desensitization of the pituitary. Aboubakr Elnashar
  • 30. Regression of symptoms occurs in the first year {Regression of pubertal characteristics, amenorrhea & decreased growth velocity}. Delayed epiphyseal fusion; treatment more effective if begun before bone age >12 yrs. Aboubakr Elnashar
  • 31. Maintain E2 at <10 pg/mL. Children require higher doses than adults for suppression. Adrenarche will continue. Treatment is continued until the epiphyses are fused or the appropriate pubertal & chronological ages are matched. Aboubakr Elnashar
  • 32. SSC do not develop by the age of 14 y or no menstruation till age of 16y Aboubakr Elnashar
  • 33. It is either : * Delayed onset: Breast bud does not appear till 13 years or menarche does not occur till 16 years . or * Delayed progreession : Menarche does not occur within 5 years after breast bud . Aboubakr Elnashar
  • 34. Causes Early cycles are anovulatory E unopposed by P endometrial hyperplasia Treatment for 3 cycles: Norethistrone acetate 5mg twice daily for 21 d or OCP Aboubakr Elnashar
  • 35. Benha University Hospital, Egypt E-mail:elnashar@hotmail.com Aboubakr Elnashar