Puberty and Lactation

Question 1

Define puberty.

Answer 1

Developmental stage during which adolescents reach sexual maturity and become capable of reproduction

Question 2

Describe the main hormonal processes involved in puberty.

Answer 2

Involves physiological processes of:

• Adrenarche = increase in production of androgens by adrenal cortex
• Gonadarche = activation of the gonads by gonadotrophins

Question 3

Identify the main gonadotrophins and androgens.

Answer 3

Gonadotrophins =  FSH and LH from pituitary
Androgens = steroid hormones e.g. testosterone, DHT, androstendione

Question 4

Identify the main physiological outcomes of puberty.

Answer 4

• Growth in stature
• Change in body composition
• Development of secondary sexual characteristics
• Achievement of fertility

Question 5

Distinguish between puberty and adolescence.

Answer 5

Puberty – physical changes (as opposed to adolescence)

Question 6

Do women have androgens at all ?

Answer 6

Yes, at low levels (serve in libido and sexual arousal)

Question 7

Define primary sexual characteristics.

Answer 7

Reproductive organs, present at birth

Question 8

Define secondary sexual characteristics.

Answer 8

Develop during puberty, not directly required for reproduction

Question 9

Define Thelarche, Pubarche, and Menarche.

Answer 9

• Thelarche = onset of breast development
• Pubarche = first appearance of pubic hair
• Menarche = onset of menstruation (i.e. ability to produce mature ova and an endometrium that could support a zygote)

Question 10

How long does the process of puberty take ? What does it begin with ?

Answer 10

4-5 years

Begins with adrenarche

Question 11

Describe the hormonal process behind adrenarche. When does it occur ? What is the trigger of it ?

Answer 11

=HPA axis (Hypothalamic-Pituitary-Adrenal axis)

• Starts at 6-8 year of age
  1) ACTH produced by pituitary
  2) Stimulates adrenal glands to secrete androgens – predominantly DHEA (dehydroepiandrosterone sulfate) (ACTH may also cause adrenal gland to result in vulva pigmentation)
  3) Increased androgen levels responsible for
• Development of pubic and axillary hair (pubarche)
• Development of pilosebaceous unit in the skin - acne
• Increases cortical bone density

Trigger not known

Question 12

List the sequence of physiological and physical events in the process of puberty in girls. State when each of these events happens.

Answer 12

1) Breast development
- first sign, usually between 8.5 and 12.5 years

2) Pubic hair growth and rapid height spurt
- occur almost immediately after breast development

3) Menarche
- average age 13
- on average 2.5 years after the start of puberty
- signals the end of growth (only around 5cm height gain remaining)

Some normal variation in order and timing

Question 13

Why does menarche signal the end of menarche ?

Answer 13

Menarche signals the end of menarche because gonadal steroids (oestrogen and testosterone) triggers closure of epiphyseal plates (so only around 5cm height gain remaining)

Question 14

Describe the hormonal process behind menarche.

Answer 14

HPG AXIS: gonadrotrophin secretions, leading to mensruation in females

• FSH and LH secreted in anterior pituitary (triggered by GnRH from hypothalamus)
• Affects ovary and results in increase in number of growing follicles
• Rise in estrogen (this leads to beginning of growth of uterus, fallopian tubes, vagina, labia, breasts, endometrium)
• Secretion of estrogen irregular (this leads to irregular anovulatory menstruation)
• Estrogen output becomes steady and rises to a critical level (this leads to LH secretion and ovulation) (as the ovaries mature, become more sensitive to gonadotropin and release more steroid hormones – when these levels become high enough to exert negative feedback on gonadotropin secretion, a cycle will develop and menarche can occur)
• Adult cyclical menstruation

Question 15

How long does it take for regulatory ovulatory cycles to develop ?

Answer 15

Up to 18 months for regular ovulatory cycles to develop

Question 16

How does body fat influence ovulation ?

Answer 16

Onset of ovulation related to critical level of body fat – triggers GnRH release.

Question 17

Describe Tanner Stages.

Answer 17

An assessment system for evaluating the stages that are seen clinically in the developmental progression through puberty (from pre-puberty i.e. stage I to adult development i.e. stage V)

Question 18

List the sequence of physiological and physical events in the process of puberty in men. State when each of these events happens.

Answer 18

1) Testicular enlargement to greater than 4mls volume
- first sign, 10-15 years (mean 11)

2) Pubic hair growth and penile growth
- Normally 2 year interval between onset of pubic hair and axillary and facial hair

3) Spermarche – appearance of sperm in seminal fluid
- mean age 13.4

4) Growth spurt
- when testicular volume is 12-15mls, after a delay of around 18 months
- Growth spurt in males later and of greater magnitude accounting for greater average final height in males

Question 19

Define precious puberty, and delayed puberty in boys.

Answer 19

Precocious puberty before 9, delayed after 15

Question 20

What Tanner stages do growth spurt and spermarche correspond to ?

Answer 20

Growth Spurt and spermarche around tanner G3-4 (ie stage 3-4 of testicular growth)

Question 21

What is the equivalent of menarche in males ?

Answer 21

Spermarche, i.e. the appearance of sperm in the urine and the onset of nocturnal sperm emissions, occurring shortly after the attainment of peak height velocity.

Question 22

Describe the hormonal process behind the development of male primary sexual characteristics, in puberty.

Answer 22

HPG AXIS: gonadrotrophin secretions, leading to spermatogenesis in males

• FSH/LH promotes testes to produce sex steroids - testosterone
• FSH promotes testicular enlargement
• Testosterone promotes penile enlargement
• Testosterone critical for spermatogenesis

Question 23

Which cells are testosterone, estrogen, progesterone, and inhibin produced by ?

Answer 23

Testosterone leydig cells and estrogen and progesterone and inhibin by sertoli cells

Question 24

Is asymmetrical testicular development normal in puberty ?

Answer 24

Asymmetrical testicular development (up to one tanner stage between testicles) at pubertal onset, can be normal

Question 25

How frequent is Transient gynaecomastia ? How long does it typically last ? Why does it occur ?

Answer 25

Transient gynaecomastia – occurs in about 50% of boys often at Tanner stage (PH) 3-4 and typically lasts <1 year ‘idiopathic pubertal gynaecomastia’ – presumably due to an imbalance in estrogenic to androgenic stimulation and excess oetrogen, lack of androgen or increased breast tissue sensitivity to oestrogen

Question 26

Identify a tool used to measure testicular volume.

Answer 26

Prader Orchidometer (from 1 mL in childhood to 25 mL in adulthood)

Question 27

What hormonal process is responsible for the development of secondary sexual characteristics in male ?

Answer 27

Virtually all dependent on testosterone and its metabolite DHT.

Question 28

Identify the main secondary sexual characteristics in male.

Answer 28

♦ Facial, underarm, pubic hair
♦ Deepening of voice (due to growth of larynx) (breaking of voice in puberty due to this androgen induced growth)
♦ Thick secretion of skin oil glands (can cause acne)
♦ Masculine pattern of fat distribution
♦ Bone growth via growth hormone secretion (sex steroids stimulate growth spurt by stimulating GH release)
-then termination via closure of epiphyseal plates (sex steroids also promote the closure of epiphyseal plates so that growth in height ceases at the end of puberty)
♦ Stimulation of muscle protein synthesis
♦ Erythropoietin stimulation giving higher haematocrit in males

Question 29

Describe the process of initiation of puberty. When does this occur ?

Answer 29

Hypothalamic-Pituitary-Gonadal axis (HPG)
-pulses of LH released at night bring about secretion of increasing levels of gonadal steroid hormones

• Some evidence for several mutations in various signalling proteins and receptors as playing a role. Kisspeptin, GABA, melatonin

1) Juvenile pause – pulsatile GnRH in mid fetal life, but gonadotrophins reduce during late infancy or early childhood and the HPA axis becomes quiescent through childhood (minor GnRH pulses mostly at night, and of low frequency and amplitude so not sufficient to trigger gonadotrophin release)– this allows further growth and development before an individual becomes sexually mature and capable of reproduction.
2) Early-mid puberty – amplification of nocturnal pulses of LH reflects the re emergence of the GnRH pulse generator and beginning of puberty
3) Mid to late puberty - daytime pulses increase
4) Adult pattern – roughly one pulse/hour with significant variation throughout the menstrual cycle.

Exact mechanism that signals start of puberty is unknown but body weight and other metabolic factors must play a key role

Question 30

Identify factors contributing to earlier puberty (in developed countries).

Answer 30

♠ Genetics – family history of early puberty. Timing correlates with mother and sisters (genetics accounts for the majority of variability in the timing of pubertal onset in developed countries)
♠ Social factors
-Lower social class and obesity = earlier menarche
♠ Geographic factorand – closer to equator, lower altitudes, urban setting
♠ Environmental exposures – endocrine disrupting chemicals – industry uses e.g. plastics, agriculture, fuels
♠ Race – onset earlier in Afro-Carribean and African-American children compared to white children

Question 31

Define menopause. When does this typically occur ?

Answer 31

Cessation of menstruation, said to have occurred after 1 year of amenorrhoea.
Occurs between 45 – 55 years (average 51.5 for the past 100 years).

Question 32

Define peri-menopause. How long does this last ?

Answer 32

The 4- to 7-year (can last up to 12) period prior to menopause during which estrogen levels begin to drop.(characterised by erratic periods)

Question 33

Identify any factors which may cause earlier menopause.

Answer 33

Smokers 6-18 months earlier than non smokers

Question 34

Explain the endocrine changes that take place during the menopause.

Answer 34

-Follicle supply diminishes, but doesn’t ‘run out’, remaining follicles not as sensitive to FSH and LH

-Oestrogen levels fall;
Positive feedback on pituitary
Increase in FSH and LH. The FSH rise precedes the LH rise; Without a follicular source, the larger proportion of postmenopausal estrogen is derived from ovarian stromal and adrenal secretion of androstenedione, which is aromatized to estrone in the peripheral circulation.

Question 35

Define neurohumoral.

Answer 35

Nerve part and chemical transmitter part in the circulation

Question 36

Describe the WHO recommendations for lactation.

Answer 36

WHO/UN advises women to breast feed exclusively for 6 months for optimal lifetime benefits (since breast milk contains all baby’s nutritional and hydration requirements for first 6 months of life)

Question 37

Identify the main benefits arising from 6 months of exclusive breastfeeding for the baby.

Answer 37

• Reduced incidence of GI, respiratory and middle ear infection (esp in LBW infants)
• Decreased risk of childhood diabetes, asthma and eczema.
• Reduced risk of lactose intolerance.
• Improved intellectual and motor development.
• Decreased risk of obesity in later life.
• Possible reduced autoimmune diseases
• 27% reduced risk of sudden infant death syndrome

Question 38

What kinds of studies study lactation in newborns ?

Answer 38

Cant do RCTs therefore mostly observational case control (retrospective) and cohort studies (prospective)

Question 39

Explain how exclusive breastfeeding for 6 months can help improve intellectual and motor development.

Answer 39

Breast milk contains polyunsaturated fatty acids (not in formula) important for brain growth and development. Physical contact of BF provides psychosocial stimulation and bonding that may have developmental benefits.

Question 40

Identify the main benefits arising from 6 months of exclusive breastfeeding for the mother.

Answer 40

• Promotes recovery from childbirth.
• Promotes return to ‘normal’ body weight (due to energy expended in production of the milk ~500calories/day extra needed, depending on activity level)
• Promotes a period of infertility (lactational amenorrhoea)
• Reduces risk of premenopausal breast cancer.
• Reduces risk of ovarian cancer.
• Possibly improves bone mineralisation (can help post MP when there is loss of bone density)

Question 41

What is the main problem associated with formula milk ?

Answer 41

Comes at a cost to the household and potential a socioeconomic cost of looking after a child with potentially avoidable illness

Question 42

Describe the anatomy of the breast.

Answer 42

• Nipple is surrounded by pigmented skin (areola)
-areola has glands that secrete an oily fluid that protects the skin of the nipple and areola during lactation and produce the mothers individual scent that attracts the baby to the breast.

• Modified sebaceous glands (alveoli) empty via lactiferous ducts that are dilated to form lactiferous sinuses which open on the surface of the nipple

• Lactiferous ducts are slightly wider at nipple to allow a little pooling of the milk
• Sebaceous glands are. microscopic exocrine glands in the skin that secrete an oily or waxy matter, called sebum, to lubricate and waterproof the skin and hair of mammals

• Adipose tissue is dominant in the non-lactating breast.
Glandular tissue only develops fully during pregnancy (“predominant tissue in the lactating breast is glandular”)

• 2 types of cells:

1) Secretory alveoli/acini - the milk producing cells (stimulated by prolactin)
2) Each alveolus is surrounded by contractile myo-epithelial cells (stimulated by oxytocin)

Question 43

Which part of the breast does the infant latch onto ?

Answer 43

Nipple

Question 44

Describe the path of the maternal milk in the breast upon lactation.

Answer 44

• Infant cannot suck milk from alveoli – need another reflex to get milk into ducts and onto nipple where can be accessed.
• From alveoli (where milk is produced) to lactiferous ducts and into lactiferous sinuses where it can pool ready to be accessed by the baby when it suckles.

Question 45

Describe the process of breast development.

Answer 45

• At birth the breast consists of lactiferous ducts without any alveoli (also male breast)
• At puberty under influence of oestrogen the ducts proliferate and masses of alveoli form at the ends of the branches
• Each cycle involves proliferative changes in the alveoli and there may be some secretory activity
• During pregnancy under the influence of oestrogen, progesterone and prolactin the glandular portion of the breast undergoes hypertrophy replacing adipose tissue
-Prolactin levels increase during pregnancy and stimulates growth and development of the mammary tissue in preparation for milk production
• From week 16 the breast tissue is fully developed for lactation but is quiescent awaiting activation
• After parturition the breast produces colostrum before mature milk production begins

Question 46

Describe the process of alveoli develoment.

Answer 46

1) Prior to pregnancy, ducts with few alveoli exist
2) In early pregnancy, alveoli grow
3) In mid-pregnancy, alveoli enlarge and acquire lumen
4) During lactation, alveoli dilate (in order to hold milk), leading to expansion of breast
5) After weaning, gland regresses

Question 47

How many lactiferous ducts are there per breast ?

Answer 47

Each lobule has a lactiferous duct

Nipple has average of 9 ducts passing to the outside

Question 48

What are the main components of lactation ?

Answer 48

1) Milk production (has to do with suckling reflex)
AND
2) Let down (aka milk ejection reflex)

Question 49

How are the processes of milk production and let down regulated ?

Answer 49

Both are controlled by neurohumoral reflexes.
→ Prolactin is the hormone responsible for milk production
→ Oxytocin is responsible for the milk ejection reflex

Question 50

Describe the hormonal control of lactation.

Answer 50

• Lactation is initiated by this precipitous drop in oestrogen and progesterone after delivery (initially high at end of pregnancy)
• Prolactin reduced at birth (after being high at end of pregnancy) BUT surges each time mother nurses baby due to nerve impulses from nipples to hypothalamus.
• When not nursing, hypothalamus produces prolactin inhibitory hormone
• Lactation inhibits FSH and LH and thus lactation interferes with reproductive function

Question 51

What happens to the hormonal control of lactation without nursing stimulus ?

Answer 51

Without nursing stimulation, no prolactin surge, alveoli regress, and loss of milk production (not possible to pick up breast feeding later))

Question 52

Describe the hormonal control of the suckling reflex.

Answer 52

Suckling stimulus inhibits the hypothalamic release of dopamine (PIF) and prolactin is released in proportion to the strength and duration of the suckling.

Levels of prolactin highest about 30 minutes after the beginning of a feed – so secreted after a feed to stimulates milk production for the next feed (I.E. The baby orders up it next meal as it suckles at its current one)

Question 53

Identify Prolactin Inhibiting Factors.

Answer 53

Dopamine

Vasoactive intestinal polypeptide

Question 54

Explain the importance of the proportional release of prolactin to the strength and duration of suckling ? Is this the case for the full duration of lactation ? Why can this proportional relationship be problematic ?

Answer 54

During the first few weeks the more a baby suckles and stimulates the nipple, the more milk will be produced – important when breast feeding is becoming established. When baby first born and needs nutrition to maintain weight etc suckling will be longer and stronger and that will promote more milk to be produced

Not such a dose effect after a few weeks. When baby being weaned and getting some other nutrition so reduced strength and duration of suckling = less milk produced.

Potential Problem: When problems with latching on, less milk produced and can negative cycle.

Question 55

What are the “side effects” of prolactin on the mother ?

Answer 55

Prolactin also helps mother feel relaxed and sleepy

Question 56

Describe the hormonal control of milk ejection reflex.

Answer 56

• Suckling stimulates neurons in the hypothalamus to synthesize oxytocin which is carried to posterior pituitary.
• The release of oxytocin into the blood stream acts on myo-epithelial cells in the alveoli – causing the ‘let down’ of milk (so baby can access milk out of the ducts and sinuses rather than being stuck in the alveoli)

Question 57

What are the “side effects” of oxytocin on the mother ?

Answer 57

Oxytocin also has a role in making mother feel calm and helps emotional bonding.
First few days after delivery oxytocin can also cause painful uterine contractions when the baby suckles.

Question 58

What are the triggers, and inhibitors of the milk ejection reflex ?

Answer 58

• Conditioned reflex (so can occur in the absence of suckling stimulus)

• let down in response to mother expecting a feed as well as from suckling, smelling or seeing the baby or hearing it cry (so works before or during a feed)
• Oxytocin release is inhibited by catecholamines - stress can inhibit the reflex (which can frequently occur when woman is trying to express milk – eg when baby not physically there eg going back to work so can be difficult to express without that stimulation)

Question 59

How is lactation inhibited during pregnancy?

Answer 59

• Prolactin controls/promotes milk production.
• Prolactin is secreted during pregnancy (from anterior pituitary), but its action is inhibited by high levels of progesterone and oestrogens and hPL (human placental lactogen).
• These steroid levels fall after parturition and milk production begins.

-However, in pregnancy, since prolactin levels increase, stimulates growth and development of the mammary tissue in preparation for milk production.

Question 60

Describe the role of prolactin in lactational amenorrhea.

Answer 60

♦ Women who exclusively breast feed their baby will delay the onset of menstrual cycles.
♦ Prolactin suppresses hypothalamic release of GnRH and therefore pituitary FSH and LH.
♦ It prevents follicular growth, ovulation and menstruation.

Question 61

What are the conditions for lactational amenorrhea to be effective ?

Answer 61

♦ LAM effective so long as:

• must be ammenorrhoeic
• baby must be exclusively breast fed
• baby less than 6 months old

Question 62

Which hormones are used as indicators for menopause ,

Answer 62

FSH is the diagnostic marker for ovarian failure, while LH is not necessary to make the diagnosis.

Question 63

How can we measure GnRH levels ?

Answer 63

GnRH too short a half life to measure so pulsatility inferred from LH levels measured (half life of 30mins compared to 300mins for FSH).

Question 64

Distinguish between the consequences of high GnRH pulse frequencies, and low GnRH pulse frequencies.

Answer 64

High GnRH pulse frequencies favor LH synthesis and secretion, while low GnRH pulse frequencies favor FSH synthesis and secretion.

Question 65

Describe the effect on continuous GnRH infusions, and pulsatile GnRH infusions, on gonadotropin release.

Answer 65

• Gonadotropin (LH/FSH) release:

• Suppressed by continuous infusion of GnRH (e.g. in childhood)
• Pulsatile administration (in hypothalamus) will lead to gonadal stimulation, maturation and production of steroid hormones