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Year 2 - LCRS - Endocrinology > Endocrine infertility > Flashcards

Endocrine infertility Flashcards

21.10.2019

1
Q

How long is the female menstrual cycle?

A
  • textbook: 28d

- reality: 25-35d

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2
Q

Normal hypothalamo-pituitary-gonadal axis in males

A

GnRH ++ LH, FSH ++Testosterone

negative feedback on H and AP by inhibin

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3
Q

What are the phases of the menstrual cycle?

A
  • follicular phase
  • ovulation
  • luteal phase
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4
Q

Describe, in detail, how the menstrual cycle works

A

LAST YEARS FLASHCARD

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5
Q

What are the possible outcomes in the luteal phase?

A
  • if implantation occurs -> pregnancy

- if implantation does not occur - endometrium I shed (menstruation)

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6
Q

What is infertility?

A
  • inability to concieve after 1 year of regular unprotected sex
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7
Q

How common is infertility?

A

1:6 couples

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8
Q

What abnormalities cause infertility?

A
  • in males (30%)
  • or females (45%)
  • or unknown (25%)
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9
Q

Primary gonadal failure

A
  • there is stimulation by the hypothalamus / AP

- gonads themselves don’t make oestradiol / testosterone

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10
Q

Secondary gonadal failure

A
  • due to hypothalamus / pituitary disease
  • low LH and FSH
  • not enough stimulation of the gonads -> low estradiol / testosterone
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11
Q

Clinical features of male hypogonadism

A
  • Loss of libido = sexual interest / desire
  • Impotence
  • Small testes
  • Decrease muscle bulk
  • osteoporosis
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12
Q

Why does male hypogonadism cause osteoporosis?

A
  • is it because Testosterone is aromatised to oestrogen and oestrogen has bone preserving qualities?
  • is it because of the anabolic effects that testosterone has on muscle and bone?
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13
Q

What are causes of male hypogonadism?

A
  • hypothalamic-pituitary disease (hypopituitarism, Kallmans syndrome, Illness/underwight (linked to leptin))
  • primary gonadal disease (congenital: Klinefelters syndrome XXY; acquired: testicular torsion, chemotherapy)
  • Hyperprolactinaemia
  • androgen receptor deficiency
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14
Q

Kallmanns syndrome

A
  • anosmia
  • low GnRH

=> delayed or absent puberty, impaired sense of smell

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15
Q

Why is anosmia common with low GnRH?

A

This is due to the fact that during embryonal development GnRH neurones and the olfactory nerves travel together

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16
Q

Investigations in male hypogonadism

A
  • LH, FSH, testosterone -> if all low do a pituitary MRI
  • Prolactin
  • Sperm count
  • chromosomal analysis (Klinefelters XXY)
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17
Q

Azoospermia

A

absence of sperm in ejaculate

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18
Q

Oligospermia

A

reduced numbers of sperm in ejaculate

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19
Q

How can you treat male hypogonadism?

A
  • replacement testosterone for all patients
  • For fertility: if hypo / pit disease -> s.c. gonadotrophins (LH & FSH)
  • Hyperprolactinaemia - dopamine agonist
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20
Q

Endogenous sites of production of androgens

A
  1. interstitial Leydig cells of the testes
  2. adrenal cortex (males and females)
  3. ovaries
  4. placenta
  5. tumours
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21
Q

What are the main actions of testosterone?

A
  1. development of the male genital tract
  2. Maintains fertility in adulthood
  3. Control of secondary sexual characteristics
  4. Anabolic effects (muscle, bone)
22
Q

How much of circulating testosterone is protein bound?

A

98%

23
Q

What can testosterone be turned into?

A
  • reduction: Dihydrotestosterone (DHT), more potent, acts via the androgen receptor
  • aromatisation: 17-beta-oestradiol (E2), acts via the oestrogen Receptor (ER) e.g. brain and adipose tissue
24
Q

Enzyme: Testosterone -> DHT

A

5-alpha reductase

25
Q

Enzyme: Testosterone -> 17-beta-oestradiol

A

aromatase

26
Q

Mechanism of action of DHT / E2

A

via nuclear receptors

27
Q

Clinical uses of testosterone

A
  • in adulthood will increase
    • lean body mass
    • muscle size and strength
    • bone formation and bone mass (in young men)
    • libido and potency

It will not restore fertility, which requires treatment with gonadotrophins to restore normal spermatogenesis!!

28
Q

What are 3 common disorders in females that cause infertility?

A
  1. Amenorrhea
  2. PCOS
  3. Hyperprolactinaemia
29
Q

Amenorrhoea

A

= absence of periods

30
Q

Primary amenorrhoea

A

failure to begin spontaneous menstruation by age 16 years

31
Q

Secondary Amenorrhoea

A

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

32
Q

Oligomenorrhoea

A

irregular long cycles

33
Q

Causes of Amenorrhoea

A
  • pregnancy / lactation
  • ovarian failure (premature ovarian failure, ovariectomy, chemotherapy, ovarian dysgenesis in Turners Syndrome 45X
  • Gonadotrophin failure (hypo/pit disease, kallmann’s syndrome, low BMI, post pill amenorrhoea)
  • hyperprolactinaemia
  • androgen excess: gonadal tumor
34
Q

How common is Turners syndrome?

A

1:5000 live female births

35
Q

Investigations for Amenorrhoea

A
  • Pregnancy test
  • LH, FSH, oestradiol
  • Day 21 progesterone (18,21,24 due to variation)
  • Prolactin
  • thyroid function tests
  • androgens (testosterone, androstenedione, DHEAS)
  • chromosomal analysis (Turners 45X)
  • Ultrasound scan of ovaries/uterus
36
Q

Treatment of amenorrhoea

A
  • Treat the cause (eg low weight)
  • Primary ovarian failure – infertile, HRT
  • Hypothalamic / pituitary disease
    HRT for oestrogen replacement
    Fertility: Gonadotrophins
37
Q

PCOS

A

= polycystic ovarian syndrome

  • Associated with increased cardiovascular risk and insulin resistance (>diabetes)
38
Q

How common is PCOS?

A

1 in 12 women of reproductive age have it.

39
Q

What are the criteria needed to diagnose PCOS?

A
  • polycystic ovaries on USS
  • oligo-/anovulation
  • clinical / biochemical androgen excess
40
Q

Clinical feature of PCOS

A
  • Hirsutism
  • Menstrual cycle disturbance
  • Increased BMI
41
Q

Treatment of PCOS

A
  • metformin (insulin sensitiser)
  • clomiphene (anti-oestrogen in the hypo-pit axis)
  • gonadotrophin as part of IVF
42
Q

Clomiphene

A
  • anti-oestrogenic in the hypothalamo-pituitary axis
  • Bind to oestrogen receptors in the hypothalamus -> block normal negative feedback -> increase in the secretion of GnRH and gonadotrophins
43
Q

Hyperprolactinaemia

A
  • prolactin secreted from the AP has a negative effect on GnRH pulsatility and decreases LH actions on gonads
44
Q

What are causes of Hyperprolactinaemia?

A
  • Dopamine antagonist drugs (Anti-emetics (metoclopramide); Anti-psychotics(phenothiazines))
  • Prolactinoma
  • Stalk compression due to pituitary adenoma
  • PCOS
  • Hypothyroidism
  • oestrogens (OCP, pregnancy, lactation)
  • idiopathic
45
Q

Clinical features if Hyperprolactinaemia

A
  • galactorrhoea
  • reduced GnRH secretion / LH action -> hypogonadism
  • prolactinoma (headache, visual field defect)
46
Q

How do you treat hyperprolactinaemia?

A
  • Treat the cause – stop drugs
  • Dopamine agonist
    • Bromocriptine
      - Cabergoline
  • Prolactinoma
    • Dopamine agonist therapy
    • Pituitary surgery rarely needed
47
Q

A male presents to endocrine 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
    1. Low LH, high FSH, Low Testosterone
    2. high LH, high FSH, Low Testosterone
    3. high LH, high FSH, high Testosterone
A

3

48
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

(this is secondary hypogonadism)

Clinically: however you could also have a normal LH and FSH but on the low end. (inappropriately normal in the context of a low oestradiol)

49
Q

Phenothiazine

A
  • antipsychotic
  • dopamine antagonist
  • can cause hyperprolactinaemia
50
Q

Which drugs can cause hyperprolactinaemia?

A

Dopamine antagonist drugs

  • Anti-emetics (metoclopramide)
  • Anti-psychotics (phenothiazines)

Oestrogen (OCP)

Year 2 - LCRS - Endocrinology (18 decks)

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