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Year 2 - Endocrinology > Endocrine Infertility > Flashcards

Endocrine Infertility Flashcards

1
Q

Reproductive Axis for Males?

A

GnRH stimulates LH and FSH release

Acts on Sertoli & Leydig cells in testis = produces testosterone & inhibin (-ve feedback)

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2
Q

Reproductive Axis for Females?

A

28-day menstrual cycle

Consists of follicular phase (similar axis to male), ovulation (unique) & luteal phase (either menstruation or pregnancy)

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3
Q

What is unique about the reproductive axis for females?

A

Occurs during OVULATION

High levels of oestradiol triggers a POSITIVE FEEDBACK = larger GnRH & LH release

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4
Q

Define Infertility

A

Inability to conceive after ONE YEAR of regular unprotected sex

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5
Q

Stats associated w. infertility?

A

1:6 couples

Males (30%)
Females (45%)
Unknown (25%)

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6
Q

2 reasons that could give rise to infertility?

A
  1. Primary gonadal failure

2. Hypo/pituitary disease

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7
Q

Primary gonadal failure?

A

GONADS fail

HIGH GnRH and LH/FSH

LOW/NO inhibin & testosterone/oestradiol (so less -ve feedback)

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8
Q

Hypo/pituitary disease?

A

Hypothalamus/pituitary fails

LOW/NO GnRH and LH/FSH

LOW/NO inhibin & testosterone/oestradiol

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9
Q

Typical disorder leading to male infertility?

A

Hypogonadism

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10
Q

Clinical features of hypogonadism in men?

A 
x loss of libido
x impotence
x small testes
x decrease muscle bulk
x osteoporosis

Essentially NO testosterone so leads to this

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11
Q

4 causes of hypogonadism in men?

A
  1. Hypothalamic-pituitary disease
  2. Primary gonadal disease
  3. Hyperprolactinaemia (less so in men)
  4. Androgen receptor deficiency
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12
Q

What can consist in hypothalamic-pituitary disease?

A

x Hypopituitarism

x Kallmans syndrome (ansomia [lack of smell] & LOW GnRH)

x Illness/underweight (low leptin, so body says not time to reproduce)

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13
Q

What can consist in primary gonadal disease?

A

Cogenital - Klinegelters syndrome (XXY)

Acquired - testicular torsion, chemotherapy

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14
Q

Potential investigations for hypogonadism in males?

A
  1. Check LH, FSH & testosterone levels - is ALL LOW, do MRI of pituitary as might be pituitary problem
  2. Prolactin (excess)
  3. Sperm count:
    x Azoospermia = ABSENCE of sperm when ejaculate
    x Oligospermia = REDUCED no. of sperm when ejaculate
  4. Chromosomal analysis e.g. Klienfelter’s syndrome
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15
Q

Potential treatments for hypogonadism in males?

A
  1. HRT - replace testosterone for ALL patients
  2. For fertility - if hypo/pituitary disease give SUBCUTANEOUS gonadotrophins (LH/FSH)
  3. Hyperprolactinaemia - dopamine agonist to inhibit prolactin
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16
Q

How do the potential treatments differ for male hypogonadism if want to get pregnant?

A

Testosterone is NOT enough - need to replace LH/FSH as well so do so subcuntaneously

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17
Q

What are the endogenous sites of androgen production?

A 
x Leydig cells of testes
x Adrenal cortex
x Ovaries
x Placenta
x Tumours
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18
Q

4 main actions of testosterone?

A
  1. Developement of male genital tract
  2. Maintains fertility in adulthood
  3. Control of 2o sexual characteristics
  4. Anabolic effects (muscle, bone)
19
Q

Characteristics of testosterone when circulating?

A

98% protein bound!

20
Q

What 2 pathways can testosterone enter when circulating?

A

5alpha-reductase:
testosterone –> DHT
x acts on AR (androgen receptor)

Aromatase:
testosterone –> 17beta-oestradiol
x acts on ER (oestrogen receptor)

21
Q

What are the clinical uses of testosterone?

A 
In adulthood, increases:
x lean body mass
x muscle size & strength
x bone formation & mass (in young men)
x libido
x potency
22
Q

Whilst in men, endocrine disorders are typically hypogonadism, what are the potential disorders in female?

A
  1. Amenorrhoea
  2. PCOS (Polycystic Ovarian Syndrome)
  3. Hyperprolactinaemia
23
Q

Define amenorrhoea?

A

Absence of periods

24
Q

Difference between 1o and 2o amenorrhoea?

A

1o - failure to begin spontaneous menstruation by age 16

1o - absence of menstruation for 3 months in woman who previously had cycles

25
Q

Oligomenorrhoea?

A

Irregular long cycles

26
Q

Potential causes of amenorrhoea?

A
  1. Pregnancy OR lactation
  2. Ovarian failure
  3. Gonadotrophin failure
  4. Hyperprolactinaemia
  5. Androgen excess - gonadal tumour
27
Q

What can consist in ovarian failure?

A

x premature ovarian failure

x Ovariectomy/chemotherapy

x ovarian dysgenesis (Turners Syndrome - 45x) - lack one chromosome

28
Q

What can consist in gonadotrophin failure?

A

x hypo/pit disease

x Kallmann’s syndrome

x low BMI - low leptin will shut off reproductive system

x Post-pill amenorrhoea (should be off it every 4 years for axis to return to normal)

29
Q

Potential investigations for amenorrhoea?

A

x Pregnancy test

x LH, FSH, oestradiol & androgen blood test (tricky however as goes up and down)

x Prolactin & thyroid function tests (hypo/hyperthroidism affects periods)

x Chromosomal analysis (i.e. Turners)

x Ultrasound scan ovaries/uterus

30
Q

Best investigative method for amenorrhoea?

A

Day 21 progesterone!

Normally a rise during ovulation so can check this to see if woman ovulated in previous cycle

31
Q

Potential treatment for amenorrhoea?

A

x Treat the cause e.g. low BMI

x Primary ovarian failure - infertile so HRT

x Hypo/pit disease - HRT for oestrogen replacement and gonadotrophins for fertility treatment

32
Q

PCOS?

A

Polycystic Ovarian Syndrome

33
Q

What is PCOS associated with?

A

Increased CVD & insulin resistance - no evidence as to why

34
Q

What criteria need to be fufilled to diagnose PCOS?

A

2 of the following:

  1. Polycystic ovaries on ultrasound scan
  2. Oligo-/anovulation (irregular OR no ovulation)
  3. Androgen excess - can be assessed clinically (e.g. hirsutism)
35
Q

Clinical features of PCOS?

A
  • Hirsuitism
  • Menstrual cycle disturbance
  • Increased BMI
36
Q

Potential treatment for PCOS?

A

Use the drugs:

  • Metformin
  • Clomiphene

OR

Gonadotrophin therapy (as part of IVF treatment)

37
Q

MOA of Clomiphene?

A

It is an anti-oestrogenic in the HPA (i.e. oestrogen antagonist)

Clomiphene binds to ER in the hypothalamus - blocks normal -ve feedback = increase in GnRH and gonadotrophin secretion

38
Q

Potential causes of hyperprolactinaemia?

A

x Dopamine antagonist drugs

x Prolactinoma

x Stalk compression due to pituitary adenoma

x PCOS

x 1o hypothyroidism

x Oestrogens, pregnancy, lactation

39
Q

Dopamine antagonist drugs?

A

Anti-emetics [treat motion sickness] (metoclopramide)

Anti-psychotics (phenothiazines)

40
Q

Explain how stalk compression due to pituitary adenoma can lead to hyperprolactinaemia?

A

May stop DA & TRH passing down the hypothalamus to pituitary

As majority -ve feedback, prevents this

41
Q

DA and TRH on prolactin?

A

DA - inhibitory (MAJOR EFFECT!)

TRH - stimulatory!

42
Q

Clinical features of hyperprolactinaemia?

A

x Galactorrhoea

x Hypogonadism - reduced GnRH secretion/LH action

x Prolactinoma - headache and visual field defect

43
Q

Potential treatments for hyperprolactinaemia?

A

x Treat the cause - stop drugs

x Dopamine agonists (bromocriptine & cabergoline)

x Prolactinoma - DA agonists or pituitary surgery

Year 2 - Endocrinology (19 decks)

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