Weeks 9,10&11 Transitions Flashcards
Effects of testosterone at puberty
- ‘Male traits’
- Bone density/growth
- Density greatly increases
- Disproportionate (facial, shoulder
width) - Muscle mass
- Increases bulk and strength
- Main driver of physeal closure in
males
Endochondral vs Intramembranous ossification
Endochondral ossification
* Occurs on a cartilage scaffold
* Most of the skeleton
* The physis
* Fracture healing (cast)
Intramembranous ossification
* Embryonic flat bones
* Subperiosteal bone growth
* Fracture healing (plate/screws)
Main effects of oestrogen in females
‘Female traits’
* Fat distribution
* Buttocks, hips, thighs
* Facial subcutaneos fat
* Bone density/growth
* Increase density
* Widened pelvis, anteverted hips
- Main driver of physeal closure in
females
What are the two stages of puberty?
Adrenarche - Awakening of the adrenal gland
- Adrenal androgen precursor secretion (DHEA, DHEA-S, and androstenedione)
- Physical signs include pubic/axillary hair development, axillary odor, and acne
Gonadarche (8-14 years): onset of true central puberty
Increased pulsatile release of GnRH from the hypothalamus
Increased pituitary release of gonadotropins LH and FSH
Breast development and growth of ovaries (estradiol and progesterone production);
Growth of testes (testosterone production)
What physical signs are associated with adrenache and gonadarche?
Adrenarche: pubic/axillary hair development, axillary odor, and acne
Gonadarche: effects of oestrogen and testosterone
What is meant by mini-puberty?
This is the second awakening of the HPG axis and occurs in infancy
What initiates pubertal onset?
Puberty is initiated with a sustained increase in pulsatile GnRH release from the hypothalamus
Which hypothalamic structure plays a key role in pubertal control?
Hypothalamic kisspeptin release plays key role in controlling pubertal onset
Kisspeptin binds to the G-protein coupled receptor (KISS1R) expressed by GnRH neurons, to initiate a sequence of downstream events
What is the main factor of pubertal onset?
Genetics
What metabolic factor has an influence on pubertal onset?
Leptin
Appears to play a permissive role in puberty initiation and maintenance
of reproductive function
Earlier initiation of puberty seen in obese children may be partly explained by higher leptin levels
What neuron produces kisspeptin?
KNDy neuron
What is precocious puberty and what is the age definition?
Precocious puberty: early development of secondary sexual characteristics before 8 years
in girls, 9 years in boys
What might enduce precocious puberty?
Benign premature adrenarche, CNS or pituitary lesions, McCune-Albright syndrome,
gonadotropin-secreting tumours or exogenous sex hormones, congenital adrenal hyperplasia (increased androgens)
What is the definition of delayed puberty?
Delayed puberty: absence or incomplete development of secondary sexual characteristics
by 13 years in girls, 14 years in boys
During puberty what might cause contrasexual development?
Contrasexual development
- More prevalent in girls due to endogenous androgen production existing anyway. Examples are polycystic ovaries, increased adrenal gland responses such as congenital adrenal hyperplasia
Less common in boys, typically caused by estrogen-secreting tumours
How do puberty blockers work?
They are GnRH agonists.
Naturally GnRH is pulsile so by applying a constant does the pituitary becomes desensitised and stops reacting to it and stops releasing LH and FSH
What are the three signals used in bone resorption?
RANKL - released by osteoblasts and osteocytes, promotes osteoclast resorption.
OPG - released by osteoblasts, binds to RANKL thus inhibiting resportion
PTH - parathyroid hormone - stimulates osteoblasts to release RANKL
Draw out the calcium homeostasis loop
What is the rough timeline of bone mass?
Peak: 27
Platau: 27-40
Decline: 40 onwards
Menopause: 46 increased decline
Two very common insufficiency fractures seen in women over 60
On the left is a distal radius fracture and in this case a Colle’s fracture
And on the right a proximal humerus fracture.
Both of these are usually sustained in a simple fall, like tripping over a rug
What is oestrogen’s role in preventing osteoporosis?
Oestrogen inhibits oscteoclasts.
It limits the amount of RANKL that osteoblasts release and promotes OPG synthesis.
Without this osteoclast scranning outdoes osteoblast cooking and there’s no food left
What is the definition of osteoporotic bone?
A decrease in bone density.
Osteoporotic bones have normal bone quality, present in reduced quantity.
Osteoclasts scran bone like saz scrans cheese, not from the edge, indiscriminantly.
Symptoms of menopause
Average age of menopause
Average age 51 years
Typical range 45–55 years
What age is considered abnormal menopause
< 40 years
What is the difference between primary ovarian insufficiency and premature ovarian failure
Primary ovarian insufficiency:
* Altered, suboptimal ovarian function and hormone production
Premature ovarian failure:
* Ovaries fully stop functioning
Hormone’s that decrease in menopause that normally negatively feedback on the hypothalamus and pituitary?
Oestrogen, Inhibin, aMH
What is the telltale hormonal sign of menopause?
Increased FSH.
This is noticed before any mentrual symptoms.
I assume we use this over oestrogen because it is affected by all three inhibiting hormones so has the most significant change.
Anatomical changes that occur in the female reproductive system during menopause.
Think
- Ovaries
- Opening of Cervix
- Vagina
- Uterus
- Fallopian tubes
What is the cause of the temperature regulation symptoms of menopause?
Vasomotor symptoms:
Abrupt drops in estrogen levels disrupt hypothalamic thermoregulatory centre
Results in miscommunication between brain and vascular system
Rusults in disruption of core body temperature and
normal temperature responses
Cardiovascular effect of menopause?
Cardiovascular disease
Explaination:
Estrogens promote vascular remodelling + elasticity,
regulate reactive dilation and local inflammatory activity
Loss of estrogen may lead to impaired endothelial function and vascular changes
What is the menopausal effect on metabilism
Decreases
Metabolic consequences:
Loss of estrogen associated with metabolic changes
and lower metabolic rate
Menopausal women have increased visceral fat and
adverse lipid profiles
What are the contraindications of menopausal hormone replacement therepy?
When would you give it?
When might you give it?
When would you definitely not?
- Risk of breat cancer or endometrial cancer
- Risk of CVD
- Active liver disease
- Undiagnosed vaginal bleeding
What are the serum FSH levels consistent with perimenopause?
What hormones does menopausal HRT consist of?
estrogen for symptoms
progestogen to protect endometrium from estrogen
What is the HRT regime for menopause in:
Women without a uterus (and no endometriosis)
Women with a uterus but recent mentrusation
With with a uterus and longer since mentstruation
Mirena is the coil
What is the treatment for menopausal loss of libido?
None
Testosterone can work but has too many side effects
Treatments for urogenital atrophy
Vaginal lubricant
Estring (sits in vagina and give a slow release of estrogen)
In H&E which stains the the nucleus and which stains the cytoplasm?
Which stains acidic substances and which is an acidic stain?
Which is pink and which is purple?
Haematoxylin is a basic stain which stains the acidic components in the cell, such as the nuclear DNA. Purple
Eosin being an acidic stain, stains the basic components of
the cytosol. Pink
What is the mechanism by which oestrogen inhibits osteoclast activity?
It inhibits the release of RANKL by osteoblasts
What is McCune-Albright syndrome (MAS)
Genetic dissorder which causes early puberty, brittle bones, cafe-au-late marks and hyperthyroidism
What is oestrogens relationship to CVD?
Complicated, it provides protection against the CVD effects of testosterone hence increased risk of CVD post menopause
However it is also the cause of CVD side effects in the combined pill.
