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LCRS Endo > Endocrine infertility > Flashcards

Endocrine infertility Flashcards

1
Q

what hormones does GnRH stimulate?

A

LH and FSH

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2
Q

what do Sertoli cells produce?

A

inhibin

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3
Q

what do Leydig cells produce?

A

testosterone

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4
Q

what is the menstrual cycle duration?

A

25-35 days

28 average

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5
Q

what are the phases of menstrual cycle?

A

follicular phase
ovulation
luteal phase

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6
Q

what is the effect of a high levels of oestradiol (E2) on the hypothalamus mid-cycle ? what stage of the menstural cycle does this indicate?

A

positive feedback increases GnRH and therefore LH release for ovulation

ovulation stage

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7
Q

what is the definition of infertility?

A

inability to conceive after 1 year of regular unprotected sex

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8
Q

what are the main two reasons for infertility?

A

1) primary gonadal failure

2) hypothalamic-pituitary disease

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9
Q

what are the hormone levels in primary gonadal failure?

A

due to gonadal failure :
high GnRH
high FSH and LH
low inhibin/testosterone/oestradiol

negative feedback means more gonadotrophin are released

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10
Q

what are the hormone levels in hypo-pit disease?

A

due to hypo-pit failure:

  • low GnRH
  • low FSH and LH
  • low/no inhibin/testosterone/oestradoil

hypothalamus and pituitary don’t react to the negative feedback signal from low production of gonadal hormones

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11
Q

what are the main 5 clinical features of male hypogonadism?

A
  • loss of libido
  • impotence
  • small testes
  • decreased muscle bulk (loss of anabolic effect)
  • osteoporosis (loss of anabolic effect)

these are the effects of low testosterone

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12
Q

what are the 4 causes of male hypogonadism?

A
  • hypo-pit disease
  • primary gonadal disease
  • hyperprolactinaemia
  • androgen receptor deficiency
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13
Q

what comes under hypo-pit disease causing male hypogonadism?

A
  • hypopituitarism
  • Kallmans syndrome (anosmia and low GnRH)
  • illness/underweight (low BMI)
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14
Q

what are 2 types of causes for primary gonadal disease in males?

A
  • congenital: Klinefelters

- acquired: testicular torsion, chemotherapy

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15
Q

what factors are investigated in male hypogonadism?

A 
- LH, FSH and testosterone 
if these are are low--> MRI pituitary 
- prolactin 
- sperm count 
- chromosomal analysis
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16
Q

what are the sperm count disorders?

A

azoospermia- absence of sperm in ejaculation

oligospermia- reduced sperm in ejaculation

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17
Q

what are the 3 treatment options for male hypogonadism?

A

HRT- to replace testosterone (address decreased muscle mass and osteoporosis)

Subcutaneous gonadotrophins- for fertility, as testosterone is not enough

hyperprolactinaemia- dopamine agonist to inhibit prolactin

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18
Q

where are testosterone/androgens produced?

A 
Leydig cells 
adrenal cortex
ovaries
placenta
tumours

prostate
liver
brain
skin

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19
Q

what are the 4 main actions of testosterone?

A
  • development of male genital tract
  • secondary sexual characteristics
  • maintenance of adult fertility
  • anabolic effects (muscle and bone)
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20
Q

how much of circulating testosterone is protein bound?

A

98%

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21
Q

what converts testosterone to DHT?

where does it act?

A

5 alpha reductase

acts on androgen receptor

22
Q

what converts testosterone to 17 beta oestradiol?

where does it act?

A

aromatase

acts on oestrogen receptor

23
Q

what are the clinical uses of testosterone in adulthood?

A
  • increase lean body mass
  • muscle size and strength
  • bone formation and mass
  • libido and potency

does not restore fertility without gonadotrophins

24
Q

what is primary amenorrhoea?

A

failure to begin spontaneous menstruation by age 16

25
Q

secondary amenorrhoea?

A

absence of menstruation for 3 months but they have had cycles before

26
Q

oligomenorrhoea

A

irregular, long cycles

27
Q

causes of amenorrhoea

A
  • pregnancy/lactation (high prolactin)
  • ovarian failure
  • gonadotrophin failure (same as male)
  • hyperprolactinaemia
  • androgen excess
28
Q

ovarian failure constitutes as/ due to

A
  • premature ovarian insufficiency
  • ovariectomy, chemotherapy
  • ovarian dysgenesis (Turner syndrome 45 X0)
29
Q

investigations for amenorrhoea

A
  • pregnancy test
  • LH, FSH, E2 and androgen blood test
  • Day 21 progesterone (to indicate ovulation has occurred)
  • prolactin, thyroid function tests
  • chromosomal analysis
  • USS of ovaries/uterus
30
Q

treatment for amenorrhoea

A
  • treat cause e.g. low BMI
  • HRT for infertility due to POI
  • HRT for oestrogen replacement
  • gonadotrophins for fertility treatment
31
Q

Polycystic Ovarian Syndrom

A

1 in 12 women
increased CVS risk and
insulin resistance risk (however no evidence why)

32
Q

what are the requirements to diagnose PCOS?

A

2 of the 3:

1) polycystic ovaries on USS
2) oligo-/anovulation - irregular/no ovulation
3) androgen excess e.g. hirsutism

33
Q

3 key clinical features of PCOS

A
  • hirsutism
  • menstrual cycle disturbance
  • increased BMI

there will be high androgen levels and high LH levels

34
Q

what is the treatment of PCOS?

A
  • metformin due to insulin resistance risk)
  • clomiphene (stimulate ovulation)
  • gonadotrophin therapy (part of IVF)
  • spironolactone (hirsutism)
35
Q

what is clomiphene?

A

anti-oestrogenic drug i.e oestrogen antagonist
binds to receptors in hypothalamus and blocks normal negative feedback
therefore increased GnRH and therefore LH/FSH

used for anovulation infertility

36
Q

what causes of hyperprolactinaemia

A
  • use of dopamine antagonists (promote prolactin secretion)
  • prolactinoma
  • pit stalk compression due to pit adenoma
  • PCOS
  • hypopituitarism
  • oestrogens, pregnancy, lactation
  • (idiopathic)
37
Q

examples of dopamine antagonists that promote hyperprolactinaemia

A

anti-emetics like metoclopramide

anti-psychotics like phenothiazines

38
Q

what is the effect of stalk compression

A

stops dopamine and TRH passing down to the pituitary

compression allowing an autonomous output

39
Q

clinical features of hyperprolactinaemia

A
  • galactorrhea
  • hypogonadism (reduce LH action)
  • prolactinoma- headache and visual field defects

prolactin associated with child bearing therefore decreases the function of sex hormones that allow reproduction hence the hypogonadism effect

40
Q

treatment of hyperprolactinaemia

A
  • treat cause e.g. drugs
  • dopamine agonists (inhibit prolactin)
  • pit surgery (rare)

dopamine is the inhibitor of prolactin

41
Q

dopamine agonists

A

cabergoline and bromocriptine

treat the prolactinoma

42
Q

what effect does dopamine have on prolactin?

A

dopamine is the main inhibitory hormone of prolactin so reduces its production

hence the use of dopamine agonists for prolactinomas (when prolactin levels are high)

43
Q

what is the effect of excess prolactin?

A

reduce GnRH, LH and FSH (pregnancy state levels)

hypogonadism

44
Q

how should Cabergoline be used for women wanting to become pregnant?

A

Cabergoline is a dopamine agonist that will reduce prolactin

  • should be stopped when pregnant as it will reduce prolactin levels so GnRH, FSH, LH will increase
  • GnRH will directly affect the corpus luteum and suppress progesterone production and therefore distrupt the pregnancy
  • they can go back to using Cabergoline after giving birth but can’t breast feed (low prolactin)

you want GnRH to be low during pregnancy

45
Q

what is investigated in diagnosing causes of ammenorhoea?

A
  • Check prolactin, FSH and LH levels (gonadotrophin failure)
  • prolactin (hyperprolactinaemia)
  • pregnancy test
  • androgen levels (excess)
  • family history for premature menopause
  • chromosomal analysis (Turner 45 XO)
  • thyroid function test
  • BMI changes
  • diet
46
Q

what does high oestrogen, low FSH and LH indicate?

A

pregnancy

47
Q

what does low LH and FSh and low oestrogen indicate?

A

hypopituitary disease
prolactinoma
low leptin

48
Q

what does high LH and FSh and low oestrogen indicate?

A

premature ovarian failure

49
Q

how much testosterone is protein bound?

A

98%

therefore inactive

50
Q

what reaction does 5 alpha reductase catalyse?

A

DHT to testosterone and vice versa

51
Q

what reaction does aromatase catalyse?

A

testosterone to 17beta oestradiol and vice versa

LCRS Endo (18 decks)

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