Endocrine Infertility Flashcards

(43 cards)

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
Oligomenorrhoea?
Irregular long cycles
26
Potential causes of amenorrhoea?
1. Pregnancy OR lactation 2. Ovarian failure 3. Gonadotrophin failure 4. Hyperprolactinaemia 5. Androgen excess - gonadal tumour
27
What can consist in ovarian failure?
x premature ovarian failure x Ovariectomy/chemotherapy x ovarian dysgenesis (Turners Syndrome - 45x) - lack one chromosome
28
What can consist in gonadotrophin failure?
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
Potential investigations for amenorrhoea?
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
Best investigative method for amenorrhoea?
Day 21 progesterone! Normally a rise during ovulation so can check this to see if woman ovulated in previous cycle
31
Potential treatment for amenorrhoea?
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
PCOS?
Polycystic Ovarian Syndrome
33
What is PCOS associated with?
Increased CVD & insulin resistance - no evidence as to why
34
What criteria need to be fufilled to diagnose PCOS?
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
Clinical features of PCOS?
- Hirsuitism - Menstrual cycle disturbance - Increased BMI
36
Potential treatment for PCOS?
Use the drugs: - Metformin - Clomiphene OR Gonadotrophin therapy (as part of IVF treatment)
37
MOA of Clomiphene?
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
Potential causes of hyperprolactinaemia?
x Dopamine antagonist drugs x Prolactinoma x Stalk compression due to pituitary adenoma x PCOS x 1o hypothyroidism x Oestrogens, pregnancy, lactation
39
Dopamine antagonist drugs?
Anti-emetics [treat motion sickness] (metoclopramide) Anti-psychotics (phenothiazines)
40
Explain how stalk compression due to pituitary adenoma can lead to hyperprolactinaemia?
May stop DA & TRH passing down the hypothalamus to pituitary As majority -ve feedback, prevents this
41
DA and TRH on prolactin?
DA - inhibitory (MAJOR EFFECT!) TRH - stimulatory!
42
Clinical features of hyperprolactinaemia?
x Galactorrhoea x Hypogonadism - reduced GnRH secretion/LH action x Prolactinoma - headache and visual field defect
43
Potential treatments for hyperprolactinaemia?
x Treat the cause - stop drugs x Dopamine agonists (bromocriptine & cabergoline) x Prolactinoma - DA agonists or pituitary surgery