Normal Puberty Hengameh Abdi MD Endocrinologist Endocrine Research
Normal Puberty Hengameh Abdi, MD, Endocrinologist Endocrine Research Center Research Institute for Endocrine Sciences Shahid Beheshti University of Medical Sciences 30 July 2015
Introduction: ü Puberty is not a de novo event but rather a phase in the continuum of development of gonadal function and the ontogeny of the hypothalamicpituitary-gonadal system from the fetus to full sexual maturation and fertility. ü During puberty, secondary sexual characteristics appear, and the adolescent growth spurt occurs, resulting in the striking sex dimorphism of mature individuals; fertility is achieved, and profound psychological effects ensue. 2
Agenda: ü Control of the onset of human puberty ü Hormonal changes during puberty ü Secondary sexual characteristics ü Adrenarche ü Other changes of puberty ü Puberty in Iran 3
(KISS 1 R) The neuroendocrine control of puberty is mediated by the hypothalamic Gn. RH-secreting neurosecretory neurons in the medial basal hypothalamus, which act as an endogenous pulse generator (oscillator). 4
5 Dual mechanism for the inhibition of puberty (Juvenile pause) Styne DM, Grumbach MM. Puberty. In: Melmed S, ed. Williams Textbook of Endocrinology. Elsevier Saunders 2011. 1088
Change in the pattern of pulsatile FSH and LH secretion Styne DM, Grumbach MM. Puberty. In: Melmed S, ed. Williams Textbook of Endocrinology. Elsevier Saunders 2011. 1088 6
Timing and onset of puberty: § Genetic neural control: Increased pulsatile release of Gn. RH caused by a balance in the inhibitory and excitatory factors Genetic factors are estimated to account for 50% to 80% of the variation in the onset of normal puberty. § Ethnicity § Environmental factors: Socioeconomic factors (such as family stress or the presence of an adult nonbiologically-related male) Nutrition and Physical activity General health Geography Environmental endocrine disruptors (environmental contaminants that may affect endocrine processes) 7
Timing and onset of puberty: (cont. ) ü Body fat and Leptin appears to be one of several factors that influence the maturation of the gonadotropinreleasing hormone (Gn. RH) pulse generator. Serum leptin concentrations increase immediately before puberty in both genders. 8
Mean plasma estradiol, FSH and LH in prepubertal and pubertal females by pubertal stage of maturation Grumbach MM. Onset of puberty. In: Berenberg SR, ed. Puberty, Biologic and Social Components. Leiden, The Netherlands: H. E. Stenfert Kroese, 1975: 1 -21. 9
Mean plasma testosterone, FSH and LH in prepubertal and pubertal males by pubertal stage of maturation Grumbach MM. Onset of puberty. In: Berenberg SR, ed. Puberty, Biologic and Social Components. Leiden, The Netherlands: H. E. Stenfert Kroese, 1975: 1 -21. 10
Laboratory information: ü Gn. RH/Gn. RH agonist test ü The basal values of serum LH and FSH measured in modern supersensitive assays: § Serum LH >0. 2 IU/L on ICMA or >0. 6 IU/L on IFMA are specific but not sensitive for the onset of puberty. ü Urine LH and FSH measured in ultrasensitive assays: § A 5 -fold rise in urinary FSH in boys and girls, with a 50 fold rise in urinary LH in boys and a 100 -fold rise in girls during puberty. 11
Laboratory information: (cont. ) ü Onset of puberty in boys is indicated by: § Testes >2. 5 cm in length (volume >3 ml) § Serum testosterone concentration >50 ng/d. L § Pubertal LH response to Gn. RH bolus § Pubertal pattern of LH pulsatility Ø Serum testosterone >20 ng/d. L predicts enlargement of testes to greater than 4 m. L by 12 months in 77% of cases and in 15 months in 100% of case. Ø Prepubertal boys have serum testosterone <10 ng/d. L. Ø Prepubertal girls have serum estradiol <5 -10 pg/m. L. 12
What to expect in girls during puberty? 13
Pubertal maturation in girls: § Increase in height velocity (rather than breast development or thelarche) is usually the first sign of puberty in girls, although breast budding is what most lay or medical observers first notice. § A substantial minority have pubic hair as the initial manifestation (pubarche). § Menarche occurs, on average, 2. 6 years after the onset of puberty (Menarche usually occurs in the 6 month period preceding or following the fusion of the second and first distal phalanges and the appearance of the sesamoid bone) üThe 95 th percentile for menarche is 14. 5 years. 14
Stages of breast development according to Marshall and Tanner • Stage 1: preadolescent; elevation of papilla only. • Stage 2: breast bud stage; elevation of breast and papilla as a small mound, with enlargement of the areolar diameter. • Stage 3: further enlargement of the breast and areola, with no separation of their contours. • Stage 4: projection of the areola and papilla to form a secondary mound above the level of the breast. • Stage 5: mature stage; projection of the papilla only, resulting from recession of the areola to the general contour. 15
Stages of female pubic hair development according to Marshall and Tanner • Stage 1: preadolescent; the vellus over the pubes is not further developed than that over the anterior abdominal wall; there is no pubic hair. • Stage 2: sparse growth of long, slightly pigmented, downy hair that is straight or only slightly curled, appearing chiefly along the labia. • Stage 3: hair is considerably darker, coarser, and curlier. The hair spreads sparsely over the junction of the pubic region. • Stage 4: hair is adult in type, but the area covered by it is still considerably smaller than in most adults. There is no spread to the medial surface of the thighs. • Stage 5: hair is adult in quantity and type, distributed as an inverse triangle of the classic feminine pattern. The spread is to the medial surface of the thighs but not up the linea alba or elsewhere above the base of the inverse triangle. 16
The sequence of events at puberty in females The stage of breast development usually progresses along with the stage of pubic hair development in normal girls, but because different endocrine organs control these two processes, discordance can occur. 17
Because girls reach PHV about 1. 3 years before menarche, there is limited growth potential after menarche; most girls grow only about 2. 5 cm taller after menarche, although there is a variation from 1 to 7 cm. The sequence of events at puberty in females Root AW. J Pediatr. 1973; 83(1) 18
What to expect in boys during puberty? 19
Pubertal maturation in boys: § Growth of the testes is usually the first sign of puberty in the male. Pubertal testicular enlargement is indicated when the longitudinal measurement of a testis is greater than 2. 5 cm (excluding the epididymis) or the volume is greater than 4 m. L. Almost all boys have an increase in testicular volume (≥ 3 m. L) prior to the appearance of penile growth and pubic hair. 20
Stages of male genital development according to Marshall and Tanner • Stage 1: preadolescent. Testes, scrotum, and penis are about the same size and proportion as in early childhood. • Stage 2: the scrotum and testes have enlarged; the scrotal skin shows a change in texture and some reddening. • Stage 3: growth of the penis has occurred, at first mainly in length but with some increase in breadth; there is further growth of the testes and scrotum. • Stage 4: the penis is further enlarged in length and breadth, along with development of the glans. The testes and scrotum are further enlarged. The scrotal skin has further darkened. • Stage 5: genitalia are adult in size and shape. No further enlargement takes place after stage 5 is reached. 21
Stages of male pubic hair development according to Marshall and Tanner • Stage 1: preadolescent; the vellus over the pubic region is not further developed than that over the abdominal wall; there is no pubic hair. • Stage 2: sparse growth of long, slightly pigmented, downy hair that is straight or slightly curled, appearing chiefly at the base of the penis. • Stage 3: hair is considerably darker, coarser, and curlier and spreads sparsely over the junction of the pubes. • Stage 4: hair is adult in type, but the area it covers is still considerably smaller than in most adults. There is no spread to the medial surface of the thighs. • Stage 5: hair is adult in quantity and type, distributed as an inverse triangle. The spread is to the medial surface of the thighs but not up the linea alba or elsewhere above the base of the inverse triangle. 22
The sequence of events at puberty in males The growth and maturation of the penis usually correlates closely with pubic hair development, because both features are under androgen control. 23
The sequence of events at puberty in males Root AW. J Pediatr. 1973; 83(1) 24
Peak Height Velocity: G (8. 3 cm/yr), B (9. 5 cm/yr) Mean age (pubertal stage): G: 11. 5 yr (2 -3), B: 13. 5 yr (3 -4) Grumbach MM. J Pediatr Endocrinol Metab. 2000; 13[suppl 6]: 1439 -1455 25
Adrenarche: § Adrenarche describes the maturational increase in adrenal androgen production, which begins at about six years of age in both girls and boys. Adrenarche seems to be unrelated to the pubertal maturation of the hypothalamic-pituitary-gonadal axis. § Premature adrenarche refers to the rise in serum concentrations of adrenal androgens that causes the appearance of the pubic hair: Boys: <9 yr African American girls: <6 yr White American girls: <7 yr 26
Adrenarche: (cont. ) § Adrenarchal androgens contribute to development of sebaceous glands and pubic hair (pubarche), and possibly to bone mineralization. 27
Other changes of puberty: Ø Voice in boys: breaking of the voice occurs at approximately 13 years, and the adult voice is achieved by about 15 years. Ø Facial hair in boys: P 3 P 5 G 5 Ø Spermarche is the age at first ejaculation (heralded by nocturnal sperm emissions and appearance of sperm in the urine): mean age of 13. 5 Ø Axillary hair: B: 14 yr African American G: 12 yr (White G: later) Ø Acne: Acne vulgaris can be the first notable sign of puberty in a girl, preceding pubic hair and breast development; In boys, progresses with advancement through puberty. 100% of boys have comedones by genital stage 5. 28
Other changes of puberty: (cont. ) Ø Vagina: Structural changes; secretion of clear or whitish discharge increases in the months before menarche. Ø Ovaries: The ultrasound appearance of the prepubertal ovary changes with pulsatile gonadotropin secretion, and a multicystic appearance occurs with more than six follicles of at least 4 mm in diameter; During prepuberty, the ovarian volume is 0. 2 to 1. 6 m. L on ultrasound scans, and after the onset of puberty, the volume increases to 2. 8 to 15 m. L. Ø Uterus: The length of the uterus increases from 2 to 3 cm to 5 to 8 cm; and the volume increases from 0. 4 to 1. 6 m. L to 3 to 15 m. L. 29
Puberty in Iran
Pubertal development in Iranian girls: Comparison with other countries Country/ Time Province Iran, 2001 -2004 Tehran, (n=4020) Mean (95% CI) 10. 15 (10 -10. 28) Mean (95% CI) 10. 48 (10. 34 -10. 62) Mean (95% CI) 14. 54 (14. 47 -14. 63) Iran, 2003 -2004 Tehran, (n=1420) Median (10 -90) 9. 74 (8. 23 -11. 94) Median (10 -90) 10. 49 (8. 86 -12. 17) Median (10 -90) 12. 68 (11. 27 -15. 96) 2. 5 th percentile: 7. 42 97. 5 th percentile: 13. 11 2. 5 th percentile: 7. 03 97. 5 th percentile: 13. 10 (n=399) Median (10 -90) 10. 14 (8. 33 -11. 95) Median (10 -90) 10. 78 (9 -12. 48) Median (10 -90) 12. 65 (11. 18 -14. 11) USA, 1997 Mean (SD) 9. 96 ± 1. 82 Mean (SD) 10. 51 ± 1. 67 Mean (SD) 12. 88 ± 1. 20 Denmark, 1991 -1993 Mean 10. 88 Mean 11. 29 Mean 13. 42 Netherlands, 1965 -1997 Mean 10. 5 Mean 10. 8 Mean 13. 15 UK, 1969 Mean 11. 1 Mean 11. 7 Mean 12. 9 Razzaghy. Azar et al. Iran, 2005 -2006 Isfahan (n=3192) Age at B 2 Age at P 2 Age at Menarche
Probability of different stages of breast development in 6– 18 -year-old Iranian girls Razzaghy-Azar M. Annals of Human Biology. 2006; 33(5/6): 628– 633 32
Probability of different stages of pubic hair development in 6– 18 -year-old Iranian girls Razzaghy-Azar M. Annals of Human Biology. 2006; 33(5/6): 628– 633 33
Probability of the occurrence of menarche in 6– 18 -year-old Iranian girls Razzaghy-Azar M. Annals of Human Biology. 2006; 33(5/6): 628– 633 34
Pubertal development in Iranian boys: Comparison with other studies Country/Time Province P 2 G 2 Iran, 2003 -2004 Tehran, (n=792) Median (10 -90) 10. 34 (6. 84 -13. 10) Median (10 -90) 9. 01 (? -11. 84) USA, 1995 Ohio (n=78) Mean (SD) 11. 2 ± 0. 8 Mean (SD) 11. 2 ± 0. 7 USA, 2001 (n=2114) African-Americans 11. 2 African-Americans 9. 5 Whites 12. 0 Whites 10. 1 35
Probability of different stages of pubic hair and genital development in 6– 15 -year-old Iranian boys Razzaghy-Azar M. Journal of Iran University of Medical Sciences. 2006 36
Timing of puberty in Iranian girls according to their living areas § The lowest age of menarche: 1) Tehran: 11. 99 ± 1. 35 yr 2) Fars: 12. 40 ± 1. 27 yr § The lowest age of thelarche: 1) Ghazvin-Zanjan: 8. 97 ± 1. 45 yr § Highest age of pubarche: 1) Kordestan-Lorestan-Ilam region: 10. 70 ± 1. 23 yr 37 Motlagh ME. J Res Med Sci. 2011; 16(3): 276 -281
Thanks for your patience!
- Slides: 38