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eLCRS - 엔도 > Endo 9: Endocrine Infertility > Flashcards

Endo 9: Endocrine Infertility Flashcards

1
Q

Describe the male hypothalamus-pituitary gonadal axis

A
  • GnRH pulses from the hypothalamus stimulates release of LH + FSH from pituitary
  • LH stimulates testosterone production in testes through leydig cells
  • Testosterone = responsible for secondary sexual characteristics + spermatogenesis
  • FSH stimulates Sertoli cells in seminiferous tubules
  • -> forms sperm + inhibit A / B
  • Testosterone has -ve feedback on hypothalamus + pituitary
  • inhibit has -ve feedback on pituitary FSH secretion
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2
Q

What are the 3 phases of the menstrual cycle?

A
  • follicular phase
  • ovulation
  • luteal phase
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3
Q

Describe the hypothalamus pituitary gonadal axis in the FOLLICULAR PHASE of females

A
  • LH stimulates production of Oestradiol + Progesterone in ovaries
  • FSH stimulates inhibit + follicular development
  • day 10: griffin follicle forms
  • initially oestrogen -ve ly inhibits LH + FSH secretion
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4
Q

Describe the hypothalamus pituitary gonadal axis in the LUTEAL PHASE of females

A
  • once oestrogen level reaches a point, it switches from -ve feedback to +ve feedback
  • which causes increase in GnRH release
  • and increases LH sensitivity to GnRH
  • This leads to a mid cycle surge in LH
  • which triggers ovulation

no implantation = menstruation
implantation = pregnancy

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5
Q

Define Infertility

A

inability to conceive after 1 year if regular unprotected sex

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6
Q

What is primary gonadal failure ?

A
  • there is defect of the gonads
  • so testes / ovaries = not producing testosterone or oestrogen so there is no -ve feedback on HPG axis
  • so you get HIGH GnRH + HIGH LH + HIGH FSH
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7
Q

What is hypothalamic / pituitary disease caused by?

A
  • caused by inability of pituitary gland to produce FSH + LH (primary gonadal failure)
  • -> so LH/FSH = low
  • -> oeastrdiol/testosteron = low
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8
Q

What are clinical features of male hypogonadism?

A
  • Loss of libido
  • Impotence
  • Small Testes
  • Decrease Muscle bulk
  • Osteoporosis
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9
Q

Give 4 main causes of male hypogonadism

A
  1. Hypothalamic-Pituitary Disease
  2. Primary gonadal disease
  3. Hyperprolactinaemia
  4. Androgen receptor deficiency
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10
Q

What are main features of Kallman’s syndrome?

A
  • testes = originally undescended

- stature = low-normal

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11
Q

How might Hypothalamic Pituitary Disease cause hypogonadism in men?

A

due to:

  • hypopituitarism
  • kallmans syndrome (anosmia + low GnRH)
  • illness/ underweight
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12
Q

give examples of Primary gonadal disease (acquired / congenital) that can cause hypogonadism in men.

A
  • congenital: Klinefleter’s syndrome (XXY)

- acquired: testicular torsion, chemotherapy

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13
Q

What investigations might you carry out on a male with hypogonadism?

A
  • LH/FSH/Testosterone levels
  • -> if all low, then MRI Pituitary
  • Prolactin levels
  • Sperm count
  • Chromosomal analysis (klinefelters)
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14
Q

What is Azoospermia ?

A

absence of sperm in ejaculate

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15
Q

What is Oligospermia?

A

reduced no. of sperm in ejaculate

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16
Q

What are possible treatment methods for hypogonadism in males?

A
  • testosterone replacement
  • if hypothalamic/ pituitary disease –> give subcutaneous gonadotrophin injections
  • -> because you need gonadotropins to stimulate testosterone release + spermatogenesis
  • for hyperprolactinaemia –> give dopamine agonist –> which has -ve effect on prolactin release
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17
Q

Give some examples endogenous sites of production of androgens

A
  • interstitial leydig cells of testes
  • adrenal cortex
  • ovaries
  • placenta
  • tumors
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18
Q

Describe 4 main actions of testosterone

A
  1. Development of male genital tract
  2. Maintains fertility in adulthood
  3. Allows control of secondary sexual characteristics
  4. Has anabolic effects on e.g muscle / bone
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19
Q

___% of circulating testosterone = protein bound

A

98%

20
Q

What enzyme converts testosterone to Dihydrotestosterone (DHT) which acts on androgen receptors

A

5-a-reductase

21
Q

What enzyme converts testosterone to 17B-oestradiol (E2) which acts on the oestrogen receptors?

A

aromatase

22
Q

DHT + E2 receptors act via what type of receptors?

A

nuclear receptors

note: they are intracellular

23
Q

What are some clinical uses of testosterone?

A

Testosterone increases:

  • lean body mass
  • muscle size + strength
  • bone formation + bone mass
  • libido + potency
24
Q

note: testosterone doesn’t restore fertility

instead you need gonadotrophin to restore spermatogenesis

A

-

25
Q

What are 3 main disorders in the female?

A
  • amenorrhoea
  • Polycystsic Ovarian Syndrome (PCOS)
  • Hyperprolactinaemia
26
Q

What is amenorrhoea?

A
  • absence of periods
27
Q

What is the difference between Primary and Secondary amenorrhoea?

A

primary = failure to BEGIN menstruation by 16 years of age

secondary = absence of menstruation for 3 months in a woman who has previously had cycles

28
Q

What is oligomenorrhoea?

A
  • irregular long cycles
29
Q

What are some major causes of Amenorrhoea?

A
  • pregnancy
  • lactation
  • ovarian failure
  • Congenital: turner’s syndrome/kallman’s syndrome
  • gonadotrophin failure
  • hyperprolactinaemia
  • excess of androgen due to gonadal tumor
30
Q

What are some methods of investigation of amenorrhoea?

A
  • pregnancy test
  • LH / FSH Oestradiol levels
  • Day 21 Progesterone
  • Prolactin / thyroid function tests
  • androgen levels
  • chromosomal analysis (turners)
  • Ultrasound scan ovaries / uterus
31
Q

How might you treat amenorrhoea?

A
  • treat cause (e.g low weight)
  • if primary ovarian failure –> HRT
  • if hypothalamic/pituitary disease –> HRT for oestrogen
  • -> gondadotrophins for fertility
32
Q

What are main features of Turner’s syndrome?

A
  • short stature
  • Cubitus Valgus
  • Gonadal dysgenesis
33
Q

Why is PCOS associated with increased cardiovascular risk + insulin resistance?

A

????

34
Q

To diagnose PCOS, you 2 of either:

A
  • polycystic ovaries on ultrasound scan
  • oligoovulation/anovulation
  • clinical/biochemical androgen excess
35
Q

what are the 3 clinical features of PCOS?

A
  • Hirsutism
  • menstrual cycle disturbance
  • increased BMI
36
Q

What are the 3 main methods of treating PCOS to achieve fertility?

A
  • Metformin
  • Clomiphene
  • -> anti oestrogen –> inhibits -ve feedback
  • Gonadotrophin therapy (as part of IVF)
37
Q

How does Clomiphene work?

A

Clomiphene has an anti-estrogenic effect on the hypothalamus-pituitary-axis

  • it binds to oestrogen receptor in the hypothalamus
  • and blocks the -ve feedback
  • this causes an increase in GnRH + gonadotrophin secretion
  • this is used in short periods –> to kickstart the HPG axis
38
Q

describe the control of prolactin secretion

what is the effect of dopamine + TRH on prolactin release?

A
  • dopamine= main hormone of prolactin control –> has -ve effect on prolactin release
  • TRH has mild stimulatory effect
39
Q

What are some causes of hyperprolactinaemia?

A
  • dopamine antagonist drugs
  • prolactinoma
  • stalk compression due to pituitary adenoma
  • PCOS
  • Hypothyroidism
  • Oestrogens (OCP)
  • Pregnancy
  • lactation
  • idiopathic
40
Q

Why does stalk compression cause hyperprolactinoma ?

A

stalk compression means dopamine can’t get through –> can’t inhibit prolactin release –> so there is high production of prolactin

41
Q

What are 3 main clinical features of hyper prolactinaemia?

A
  • galactorrhea
  • reduced GnRH secretion/ LH action –> causes hypogonadism
  • prolactinoma
    (headache / visual field defect)
42
Q

How would you treat hyperprolactinaemia?

A
  • treat the cause
  • if prolactinoma –> use dopamine agonist therapy
    e. g bromocriptine/cabergoline
  • -> also causes decrease in size of tumor if caused by prolactinoma
43
Q

A male presents to end clinic who has had bilateral orchidectomy (removal of testes)

what would you expect his blood results to show

  1. Low LH, Low FSH, Low Testosterone
  2. Low LH, high FSH, Low Testosterone
  3. high LH, high FSH, Low Testosterone
  4. high LH, high FSH, high Testosterone
A
  1. high LH, high FSH, Low Testosterone
44
Q

A young woman presents to endocrine clinic who complains of secondary amenorrhea and galactorrhea. Her GP measured her prolactin at 4500 (high). What would you expect her blood results to show:

  1. Low LH, Low FSH, Low oestradiol
  2. Low LH, high FSH, Low oestradiol
  3. high LH, high FSH, Low oestradiol
  4. high LH, high FSH, high oestradiol
A

1

45
Q

how does anosmia occur in gonadal failure?

A
  • if GnRH fails to migrate properly through olfactory –> doesn’t reach brain –> lack of GnRH + sense of smell (anosmia)
46
Q

How does hyperprolactinaemia cause infertility

A

gnRH = released in pulses

hyperprolactinaemia switches it off

eLCRS - 엔도 (20 decks)

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