Sex hormones (18) Flashcards
How do we define puberty?
- maturation of reproductive organs
- production of sex-steroids
- develop 2y sexual characteristics
- attain capability to reproduce
What is Tanner Staging/how is it used to describe development?
Thelarche= breast development in girls (1= pre pubertal…5= adult breasts)
Testicular volume in boys (1.5ml prepubertal…adult size testes >15mls)- assessed using orchidometer
Pubarche= pubic hair onset in both (1=prepubertal…5= adult hair)
What is gonadarche?
activation of gonads by HPG axis
What is menarche?
onset of menstrual cycles
What is spermarche?
onset of sperm production
What is adrenarche?
onset of androgen production by adrenal glands
What 2y sexual characteristics are caused by estradiol in girls?
- breast development
- hair growth: pubic and axillary
- sweat gland changes: oily skin/ acne
- changes to external genitalia
What 2y sexual characteristics are caused by testosterone in boys?
- deepening of voice
- hair growth: pubic then axillary, facial
- sweat gland changes: oily skin/acne
- changes to external genitalia
What age is the onset of puberty for girls?
8-13
What age is the onset of puberty for boys?
9-14
What is the difference in the stage at which peak height is obtained for girls/boys?
in girls: at around tanner stage 2-3
in boys: 3-4
What are hormonal changes like during puberty?
adrenarche: DHEA (adrenal androgen) gradually increase
gonadarche: LH + FSH inc.
testosterone inc. in boys
oestradiol inc. in girls
What is GnRH and how can we describe its secretion?
gonadotrophin releasing hormone
- pulsatile secretion
Why are LH and FSH called gonadotrophins?
they stimulate the gonads (testes/ovaries) to make testosterone/oestrogen
How does GnRH secretion vary with age?
- in late foetal life and early neonatal life: activation of HPG axis (“mini puberty”)- important for early maturation of gonads
- in childhood: quiescence (inactivity) of HPG axis
- as puberty is approached: inc. nocturnal GnRH pulsatility
- as puberty is established: normal pulsatile GnRH secretion
How do we classify delayed puberty?
doesn’t start by 14yrs
more common in boys
How do we classify precocious puberty?
starts before 8yrs
more common in girls
When does menarche usually occur?
- 3yrs after thelarche/ soon after peak height velocity
- mean age= 12.7yrs
When do we classify primary amenorrhoea?
period starting later than 16yrs
When do we classify secondary amenorrhoea?
- periods start but then stop for at least 3-6 months
N.B. common for periods to be irregular/anovulatory
How long is a normal menstrual cycle in an adult woman?
28 days (24-35) relatively stable from month to month
When do we classify oligo-menorrhoea?
- few periods over a year
- irregular/infrequent periods >35 day cycles
- or 4-9 cycles per year (less= amenorrhoea)
What are the hormone levels during the follicular phase (pre-ovulatory)?
- FSH rises- follicle stimulating hormone
- 2-3 follicles start to grow
- produce E2 (estradiol) and inhibin B–> -ve feedback to reduce FSH
- smaller follicles die off bc lack FSH (atresia) during ‘FSH window’
- bigger follicle survives bc less dependent on FSH- Graafian follicle
- follicle produces E2–> levels inc.
- switch to +ve feedback
- induces LH surge- causes ovulation (release of egg from follicle)
What are the hormone levels during the luteal phase?
(low FSH and LH)
corpus luteum produces progesterone (most important) and oestradiol
What is the purpose of B-hCG in pregnancy?
maintains continual production of progesterone by corpus luteum
(emulates LH- binds to receptors)
What would happen if GnRH was secreted in a non-pulsatile fashion?
continuous non-pulsatile administration of GnRH causes decreased LH/FSH secretion–> dec. testosterone/oestrogen
What is hypogonadism?
reduced function of testes/ovaries- low testosterone/ oestrogen levels
What is primary hypogonadism?
caused by direct damage to gonads
e. g. infection/trauma/testicular cancer/menopause
- ->dec. sex steroid levels
- -> reduced -ve feedback to hypothalamus and pituitary
- -> inc. LH+FSH
What is secondary/hypogonadotrophic hypogonadism?
e.g. pituitary tumour, hyperprolactinaemia
–> dec./not inc. LH+FSH levels
–> dec. sex steroid levels
(N.B. despite dec. sex steroid and -ve feedback–> no inc. in LH/FSH from pituitary)
What happens in menopause in terms of the HPG axis?
example of 1y hypogonadism ovaries reduced function --> dec. oestrogen (E2) --> reduced -ve feedback --> inc. FSH(/LH) bc low inhibin
What are symptoms of menopause?
lack of estradiol
- dry skin/ thin hair
- hot flushes/sleep disturbance
- mood disturbance
- osteoporosis (bc E2 stimulates osteoblasts)
- sexual dysfunction- dryness, libido
- amenorrhoea (no period for 1yr/ infertility)
- climacteric- irregular periods in years approaching menopause
How do we treat menopause?
hormone replacement therapy- oestrogen
N.B. adding progesterone prevents risk of endometrial hyperplasia and cancer bc otherwise lining would continue to grow + not shed
*How can we assess ovarian reserve?
AMH (anti-mullerian hormone) levels- produced by Sertoli cells in ovaries- v. low at menopause
What age does menopause occur?
median age= 51yrs
range= 45-55
<40yrs= premature
What is premature ovarian insufficiency (POI)?
- same symptoms as menopause but early
- high FSH and low E2
- 20% can get pregnant
What are causes of POI?
- autoimmune
- genetic e.g. Fragile X syndrome, Turner’s
- cancer therapy: previous radio/chemotherapy
What is the binding of ‘total testosterone’ in circulation?
- 60% SHBG bound testosterone–> unavailable
- 38% albumin-bound testosterone–> bioavailable (bound weakly)
- 2% free testosterone–> ACTIVE
What causes ‘late onset hypogonadism’ in males?
SHGB increases, so more of total testosterone binds–> free testosterone reduced
How do testosterone levels vary throughout the day?
high in morning (before 11am)- gradually reduces during day
ideally measured when fasting as sugar can dec.
What are symptoms of testosterone deficiency?
- sexual dysfunction: dec. libido, erectile dysfunction (esp. loss of morning erections)
- hair growth- frequency of shaving change?
- energy levels- wellbeing, fatigue
- body composition- inc. fat? dec. muscle mass? gynaecomastia (male breast enlargement)
- spermatogenesis reduced
- bone health (inc. risk of osteoporosis bc conversion to oestradiol)
What is the action of aromatase in fat tissue, ovaries/testes and bone?
converts testosterone–> 17B-oestradiol
and
androstenedione–> oestrone
N.B. low testosterone–> low oestradiol–> inc. risk of osteoporosis
What factors increase the action of aromatase?
age, OBESITY, insulin, gonadotrophin, alcohol
How would we treat breast cancer that is sensitive to oestrogen?
use aromatase inhibitor e.g. tamoxifen
to reduce prod. of oestradiol
How would we treat prostate cancer where we don’t want DHT?
use 5-alpha reductase inhibitor e.g. finasteride
