Puberty and Reproductive Endocrinology

Question 1

Define puberty

Answer 1

• stage of physical maturation in which an individual becomes physiologically capable of pro-creation
• physically changes include
  
  • growth spurt,
  • secondary sex characteristics,
  • menarche/ spermatogenesis

Question 2

What physical changes take place in girls from ages 8 - 16yrs

Answer 2

• GROWTH SPURT 8 - 14 yrs
  
  • 6 - 10 cm / yr peak
  • 2.5 yrs duration
• BREAST GROWTH 8 - 13 yrs ( 11 yrs )
  
  • (Thelarche), Usually the first sign
  • before or after these ages would be seen as precocious or delayed puberty
• PUBIC HAIR 9 - 13 yrs
  
  • (Pubarche), 1st Pubertal Sign in 25% of girls
• AXILLARY HAIR 9.5 - 15 yrs
  
  • (Adrenarche), May follow menarche
• MENSTRUATION 10 - 16 yrs ( 13 yrs )
  
  • (Menarche)
  • signals the fusion of the growth plates

Question 3

What endocrine changes occur during puberty?

Answer 3

• neural mechanisms that suppress of GnRH are decreased at puberty
• Pulsatile GnRH release (nocturnal) every 90-120 min from 6 to 9 years
• increased GnRH leads to increased FSH, LH
• Ovaries/testes become sensitized to the effects of FSH and LH
  
  • this is the Final phase: development of positive/negative feedback mechanism
• ACTH stimulates the adrenals –> Pubic & Axillary hair development

Question 4

What changes happen to the Testes during puberty?

Answer 4

• Production of gametes (sperms)
  
  • Sertoli cells under FSH control
• Production of androgens (Testosterone)
  
  • Leydig cells under LH control
  • 95% from testes, 5% from adrenals
• Testosterone in blood – converted to DHT in the target organs
• Enlarging testicles is a sign of puberty
  
  • in quarry precocious puberty, the testicular volume of 4ml signals the start of puberty
  • in clinical assessment, an orchidometer is used

Question 5

Explain the Ovarian Cycle

Answer 5

• Follicular phase
  
  • Initially Oestrogen rises due to (FSH) with LH surge in mid cycle (ovulation)
  • Ovulation occurs
• Luteal phase
  
  • Negative feedback after ovulation
  • No further ovulation in the same cycle
  • rise in progesterone as the endometrium thickens
  • at the end of the luteal phase menstration occurs

averagely 28 days

Question 6

What is the age of Menarche?

Answer 6

• Related to general health, genetic and nutritional factors
• Mean age is falling at a rate of 4 months per decade
  
  • Mean age in 1840 = 16.5 y; 1990 = 12.8 y
• One in 8 girls now reaches menarche while at primary school
  
  • tall in primary school (early presentation of menarche may mean slower growth later on)
• Bodyweight and % fat is also important
  
  • Mean weight at menarche is 47.8kg
  • 16-24% fat
  • Athletes, patients with anorexia – late onset

Question 7

What is Adrenarche?

Answer 7

• Adrenal androgens – responsible for axillary and pubic hair
• ACTH stimulates zona reticularis of the adrenal cortex
• DHEAS & Androstenedione
  
  • Girls – starts by 6, adequate levels by 8
  • Boys – starts by 8, adequate levels by 10
    
    • this is becoming more premature as obesity increases in the population

Question 8

What is the chronological order of puberty for girls?

Answer 8

• average age 10.9 yrs (8.5-13.3yrs) last between 2-3 yrs
• Growth spurt: 12.2 yrs
• Breast development
• Pubic hair
• Axillary hair
• Menarche: average age of 12.9 yrs (10-15 yrs)

Question 9

What is the chronological order of puberty for boys?

Answer 9

• average age is 11-2 years (9.2-14.2), overal takes 3-5 years
• Testicular volume
• Penile length
• Pubic hair
• Growth spurt: 13.9yrs
• Axillary / Facial hair
• Deep voice: average age is 14/6yrs (12-17yrs)

Question 10

What is Precocious Puberty?

Answer 10

• Presence of true pubertal features at a young & inappropriate age
• Central or True precocious puberty
  
  • Gonadotrophin dependent
• Peripheral or Pseudo-precocious puberty
  
  • Gonadotrophin independent
• can have normal variants of premature, thelarche or adrenarche that is not associated with the entire puberty cascade

Question 11

What is this an image of?

• what does it indicate?
• what are the symptoms?

Answer 11

• Hypothalamic Hamartoma - MRI
  
  • Non-neoplastic, homogenous sessile mass, iso-intense to brain parenchyma in the region of the tuber cinerarium in the hypothalamus
  • more prevalent in boys than girls
• This is a cause of True/ Central precocious puberty
• blood clots in nappy, bilate breast buds, high gonad hormones,
• older bone age

Question 12

What is the treatment for True/ central precocious puberty?

Answer 12

• Long acting LHRH analogue therapy
  
  • sustained supra-physiological LHRH levels
  • causes cessation of gonadotrophin release- stops the further pubertal progression
• Pubertal progression when the treatment is stopped

Question 13

What would be seen in normal premature thelarche?

Answer 13

• Isolated breast development
• usually seen in children < 2-3 yrs of age
• just a rise in FSH not LH

Question 14

What would be seen in normal premature adrenarche?

Answer 14

• Isolated pubic hair development
  
  • can be the first sing of puberty of some
• still needs to be investigated for other causes e.g androgen producing tumour
  
  • urine sample: for urinary steroid profile

Question 15

Explain the presentation/ cause of pseudo-precocious puberty in females

Answer 15

• Iso sexual (Feminizing)
  
  • (MAS) McCune-Albright Syndrome, Ovarian, Adrenal, Other, Exogenous estrogens
• Hetero sexual (Masculinizing)
  
  • (CAH) Congenital Adrenal Hyperplasia, Ovarian, Adrenal, Exogenous androgens

Question 16

Explain the presentation/ cause of pseudo-precocious puberty in males

Answer 16

• Iso-sexual or masculinising
  
  • CAH, Adrenal/Leydig cell tumor
• Hetero-sexual or feminising
  
  • Adrenal cause

Question 17

What is Congenital Adrenal Hyperplasia?

Answer 17

• a gene mutation which affects the steroid biosynthesis pathway
• most commonly affects the 3-beta hydroxysteroid dehydrogenase pathway (3ßHSD)
  
  • decrease in Aldosterone
  • decrease in cortisol
  • increase in Testosterone
• the type of metabolites found in urine steroid profiles indicates what type of CAH an individual has
  
  • needs to be identified early in infants due to risk of salt wasting

Question 18

Review the steroid biosynthesis pathway of CAH

Answer 18

Question 19

What are key concerns of delayed puberty?

Answer 19

• possibly genetic component
  
  • look at genetic profile potentially
    
    • Turner syndrome in females
    • Klinefelter Syndrome in males
• fear that puberty will never occur
  
  • emotional and psychological upset of immaturity especially with short stature
• Long term sequelae: reduced bone mineralization

Question 20

What is Klinefelter Syndrome?

• aetiology
• presentation
• treatment

Answer 20

• genetic condition where there is an extra X chromosome
  
  • 1:1000 male infants
  • causes androgen deficiency
• usually presents with
  
  • no pubertal progress
  • learning difficulties
  • Tall (98th centile)
  • young bone age
  • reduced testicular volume
  • azoospermia/ infertility
  • micro genitalia
• treated with lifelong testosterone replacement therapy

Question 21

What is Turner Syndrome?

• aetiology
• presentation
• treatment

Answer 21

• a genetic abnormality where a female is missing an X chromosome
  
  • occurs in 1:2000 live female births
  • Turner Mosaic karyotype
• Presents with
  
  • triad: short stature, streak gonads, primary amenorrhoea
  • dysmorphic features - webbing of neck, cubitus valgus
  • coarctation of aorta horseshoe kidney
  • recurrent ear infection
  • widely spaced nipples
  • elevated gonadotrophins
  • early signs in lymphodema
• Treat with
  
  • Growth Hormone Therapy early on
  • pubertal induction + ongoing HRT
  • active monitoring to detect co-morbidities
  • assisted conception

Question 22

What is another cause of delayed puberty in male adolescence?

Answer 22

• Gonadotrophin deficiency
  
  • Kallman’s gene analysis could be done
  • an MRI may be done
• absent smell sensation
• will be on lifelong testosterone replacement therapy
• low testicular volume, no rise in any gonadal axis hormones

Question 23

How is puberty staged?

Answer 23

• Tanner staging
• From 1-5
  
  • 1. testicular volume <3ml, no pubic hair elevation of papilla only
  • 5. adult size and shape penis spread to the medial surface of the thighs, recession of the areola to the counter of the breast projection of papilla only

Question 24

What affects the timing of puberty?

Answer 24

• genetic, likely to go through puberty at a similar time to your parents
• dietary factors
  
  • lower weight/ weight loss –> later puberty
  • higher weight/ weight gain –> earlier puberty
• Genetic central gonadal hormone effects
• idiopathic factors

Question 25

What are the effects of Testosterone?

Answer 25

* increased aggression and libido * enlargement of the larynx * the male pattern of pubic hair growth * maturation of the genitalia * muscle development * sperm production * bone growth * acne

Question 26

Go over the key feature of male reproductive endocrinology

Answer 26

* LH works on the Leydig cells * produces Testosterone: has a negative feedback * FSH works on Seminiferous tubule * to produce sperm

Question 27

Go over female reproductive endocrinology - Ovulation

Answer 27

* in the follicular stage of the ovarian cycle, FSH matures primordial follicles to primary follicles * the combined action of LH and FSH then converts the one follicle into secondary follicle then into a Mature Graafian * as oestrogen levels rise the mature Graafian follicle releases it's egg * the corpus luteum (the remnants of the follicle without the egg) go on to release progesterone and estrogen * this thickens the lining of the endometrium, increasing blood flow in preparation for implantation of a viable egg * If this doesn't occur then menstruation occurs as the corpus luteum ages

Question 28

Go over the female reproductive endocrinology - hormones and site of cell action

Answer 28

* FSH works on _Granulosa cells_ in the ovaries to produce Oestrogen and progestins, Activin, and Inhibin * LH works on _Theca cells_ to produce Progestins and Androgens * LH stimulates Granulosa cells

Question 29

Review the action of gonad hormones on the Thecal and Granulosa cells

Answer 29

* In Thecal cells * LH binds to the receptor activating the cAMP, protein Kinase A chain * this stimulates cholesterol to be converted to _Androstenedione_ * Androstenedione moves into the granulosa cell * FSH has bound to the receptor in the granulosa cell and activated the protein kinase A pathway * this allows Androstenedione to be converted to Estradiol * Estradiol then leaves the cell and enters the blood

Question 30

What is the role of oxytocin?

Answer 30

* In Breast-feeding * contracts the myoepithelial cells of the alveoli in a classic neuroendocrine reflex * in Childbirth * in late pregnancy, myometrium becomes sensitive to oxytocin and creates a positive feedback loop of cervical stretching and uterine contractions