sex hormones Flashcards
what is puberty
maturation of reproductive organs
production of sex steroids eg oestradiol/testosterone
development of secondary sexual characteristics
attain capability to reproduce
how is puberty graded
Tanner staging
in girls, how is puberty graded
thelarche - development of the breast
stages 1-5
in boys, how is puberty graded
growth of testes
testicular volume
stages 1-5
compared to beads called prader orchidometer
in both boys and girls, how is puberty graded
onset of pubic hair
pubarche
stages 1-5
what does gonadarche mean
activation of the gonads via HPG axis
what does thelarche mean
onset of breast development
what does menarche mean
onset of menstrual cycle
what does spermarche mean
onset of spermatogenesis
what does adrenarche mean
adrenal androgen production (starts ~2 years before gonadarche)
what does pubarche mean
onset of pubic hair
what are the 2ndary sexual characteristics in females caused by
effects of oestradiol
what are the 2ndary sexual characteristics in females
breast development
hair growth - pubarche, axillary
sweat gland composition - skin oiliness, acne
changes to external genitalia
what are the 2ndary sexual characteristics in males caused by
effect of testosterone
what are the 2ndary sexual characteristics in males
deepening of voice
hair growth - pubic, axillary and facial
sweat gland composition - skin oiliness and acne
changes to external genitalia
what is the 1st sign of puberty in girls
thelarche
what is the late sign of puberty in girls
menarche
what are the measurements in ml for testicular size for boys at different stages of puberty
prepubertal <4mls
adult size > 15mls
what is adrenarche and where does it happen in girls
activation of adrenal androgen production
in girls this happens in the ovaries and adrenal glands
where does adrenarche happen in boys
in the testes and adrenal gland
Name 2 androgens
testosterone and androstenedione
where do some androgens (DHEA/DHEAS) tend to be secreted more from
the adrenal glands
in which gender is adrenarche more important for pubarche for
girls, as boys have testosterone so they are less reliant on adrenal androgens
what is the first sign of gonadarche
activation of the HPG axis - hypothalamic pituitary gonadal axis
what normal secretion is pulsatile
GnRH - gonadotrophin releasing hormone
what does GnRH do
stimulates the rest of the axis
stimulates gonadotrophs in the pituitary to secrete LH/FSH (gonadotrophins - stimulate growth in testes/ovaries)
what happens to the HPG axis over time
in childhood = quiescent
closer to puberty = increased nocturnal GnRH pulsatility and eventually normal pulsatile generation during the day
during late pregnancy and neonatal life there is early activation of the HPG axis
when does menarche start
~2-3 years after thelarche
soon after peak height velocity
mean age = 12.7 years (range 10.7-16.1)
what is primary amenorrhoea
menarche later than 16 years is regarded as abnormal
what is secondary amenorrhoea
periods start and then stop for at least 3-6 months
most common physiological cause = pregnancy
how long is it common for periods to be irregular/anovulatory for
18 months
how long is the menstrual cycle in adult women
28 day cycle (24-35 days)
+/- 2 days each month
measured from the 1st day of full bleeding
what is the definition of amenorrhoea
absence of periods
no periods for at least 3-6 months
or up to 3 periods per year
what is oligo-menorrhoea
few periods
irregular or infrequent periods >35 cycles
4-9 cycles per year
what is a follicle
in ovaries there are follicles and each follicle is a fluid filled sac containing an egg
what do follicles contain
granulosa and theca cells which support the development of the egg
describe the follicular phase - where FSH rises
FSH stimulates follicle to grow
2-3 follicles start to grow
and they produce oestrogen (oestradiol - E2) and hormone inhibin B - both of which negative feedback to hypothalamus and pituitary gland to reduce FSH levels
as FSH decreases, smaller follicles dependent on FSH for growth die - atresia
larger follicles that are less FSH dependent are the dominant follicles
the dominant follicles grow further > E2 produced (at low levels = negative feedback but at high levels = positive feedback - stimulating the hypothalamus and pituitary to make gonadotrophins mostly LH)
mid cycle LH surge - induces ovulation (release of egg from follicle and remainder becomes corpus luteum) which produces progesterone and oestradiol
what peaks about 7 days after ovulation
progesterone (due to corpus luteum?)
what happens at day 21 if levels are too high
ovulation
describe the uterine cycle
as progesterone falls down - induces menstrual bleed
first few days = menstrual bleed
next 10 days = proliferative phase
what happens in the proliferative phase
(E2 is gradually increasing - important for proliferation of new epithelial cells in endometrium)
- endometrial lining regrows
- growth of new epithelial cells
- gland proliferation
- increase in stroma/arterioles
what happens in the secretory phase
progesterone
- transformation to be receptive for implantation
- increased volume of stromal cells»_space;> thick spongy lining
- cork screw shaped glands secreting glycogen
- coiling and lengthening of spiral arteries
what is ovulation
release of egg > goes through fallopian tube
where it meets the sperm and becomes fertilised (ampulla region) = embryo
travels to endometrium and implants around day 21
if the egg successfully implants in the endometrium, what does it produce and what does it do
beta hCG (pregnancy hormone) - stimulates LH receptors as LH surge was important for the corpus luteum > needs LH > maintains functions of the corpus luteum which will survive making progesterone and E2 maintaining the pregnancy
what happens if no hCG is produced
corpus luteum dies off > no more progesterone made > endometrium sheds > bleeding = new menstrual cycle
what happens if GnRH is absent or not pulsatile
reduced LH/FSH > reduced ovarian/testicular function
continous non-pulsatile administration of GnRH causes decreased LH/FSH secretion
can we measure GnRH
no ofc not silly
we use LH as a surrogate marker instead
in the follicular phase how often is every LH pulse
every 90-120 mins
in the luteal phase, how often is every LH pulse
slowed by progesterone
every 3-4 hours
what is hypogonadism
decreased function of the gonads
in males, what is hypogonadism
testes - decreased testosterone
in females what is hypogonadism
decreased oestrogen
causes of hypogonadism
problem with the gonads (testes/ovaries)
problem with hypothalamus/pituitary gland not making enough LH/FSH
- infections
- trauma
- cancer of testes
what is primary hypogonadism
problem with the gland that is supposed to secrete that hormone (eg testicular or ovarian damage)
what happens in hypogonadism
normally makes testosterone or oestradiol - negative feedback on hypothalamus and pituitary but now there is reduced negative feedback so more LH/FSH
most common cause of hypogonadism in females
menopause > ovaries stop functioning > decreased oestrogen > less negative feedback > high FSH/LH
which hormone is more related to reducing FSH for menopause
inhibin B as inhibin drops because ovaries stop making it > increased FSH
what causes secondary hypogonadism
decreased function of hypothalamus/pituitary
- pituitary tumour
- high prolactin
what is hypogonadotropic hypogonadism
problem with the gland that controls hormones that stimulates glands that make that hormone
symptoms of menopause
due to lack of E2 - oestradiol
- skin dryness/hair thinning
- hot flushes/sweating/sleep disturbance
- mood disturbance
- osteoporosis - decreases bone mineral density (BMD) as E2 stimulates osteoblasts
- sexual dysfunction - vaginal dryness, low libido
- weight gain
- amenorrhoea - perimenopause - within a year of no periods, postmenopause - after 1 year of no periods
- cessation of fertility
- climacteric - irregular periods in years closer to menopause
treatment for menopause
menopause hormone therapy (MHT)
- oestrogen replacement - oestrogen stimulates the endometrium to proliferate
- add progesterone - if endometrium is intact to prevent risk of endometrial hyperplasia/cancer
what are ovarian reverse markers
AMH levels (antimullerian hormone)
peaks at adult
falls off towards menopause
to assess ovarian reserve
what cells make AMH
granulosa cells in ovaries
what age does menopause occur
45-55 years
median age 51
what age does premature menopause occur
<40 years
what condition has the same symptoms as menopause and what is its diagnosis
early menopause - premature ovarian insufficiency (POI)
high FSH >25 iU/L (2 times at least 4 weeks apart)
what are causes of POI
autoimmune
genetic - fragile X syndrome/Turners syndrome (XO)
previous cancer therapy - eg. chemo/radiotherapy
what is andropause
fall of testosterone
peak testosterone = 40 years
most of testosterone is..
SHBG bound testosterone - stronhly and albumin weakly binds to testosterone
free testosterone 2% is active
late onset hypogonadism
what happens to SHBG as you grow older
increases with age - produced in liver > less free testosterone
testosterone has diurnal rhythm - highest in the morning - measure before 11am
can fall up to 20% with sugar > measure while fasting ideally
testosterone deficiency symptoms
sexual dysfunction - low libido
erectile dysfunction - loss of early morning erections
reduced hair growth
reduced energy levels - fatigue
mood disturbance
body composition - increased fat/reduced muscle mass
gynaecomastia - breast enlargement in men
decreased spermatogenesis - high levels of intratesticular testosterone
bone health - via conversion to oestrogen
what can testosterone be converted into
testosterone > oestrogens by aromatase in adipose tissue
testosterone > dihydrotestosterone by 5 alpha reductase in eg prostate/scalp
DHT is more potent ligand for androgen receptor
