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Yr 2 LCRS - Endo > 9 - Endocrine Infertility > Flashcards

9 - Endocrine Infertility Flashcards

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1
Q

Outline the hypothalamo-pituitary-gonadal axis

A

Hypothalamus
- Gonadotrophin Releasing Hormone (GnRH)

Pituitary
- LH/FSH

Gonads
- Testosterone

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2
Q

What hormone exerts negative feedback on the hypothalamo-pituitary-gonadal axis at the levels of the hypothalamus and pituitary?

A

Testosterone

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3
Q

What is the average menstrual cycle length?

A

28 days

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4
Q

What are the three phases of the menstrual cycle?

A

Follicular Phase

Ovulation

Luteal Phase

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5
Q

What occurs in the follicular phase?

A

Same as in men

GnRH/LH/FSH

Follicles in ovary start to grow

Oestradiol levels increase due to increased follicular cell size

High estradiol positively feeds back to hypothalamus

Big surge in GnRH

Therefore, big surge in LH and FSH

This causes egg maturation

Eventually, causes ovulation

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6
Q

What happens if implantation of a fertilised ovum does not occur?

A

Endometrium is shed

= MENSTRUATION

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7
Q

Define infertility

A

Inability to conceive after 1 year of regular unprotected sex

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8
Q

How many couples does infertility affect?

A

1 in 6

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9
Q

Within couples, where does the cause of infertility lie by percentage?

A

In Males = 30%

In Females = 45%

Unknown = 25%

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10
Q

What is Primary Gonadal Failure?

A

Testes/Ovaries stop functioning

Defect at level of the gonads

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11
Q

What occurs in Primary Gonadal Failure?

A

Less negative feedback from testosterone

High GnRH

High FSH/LH

Low testosterone/oestradoil

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12
Q

What is Secondary Gonadal Failure?

A

Disease/dysfunction of the hypothalamus or pituitary

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13
Q

What occurs in Secondary Gonadal Failure?

A

Low LH/FSH

Low testosterone/oestradiol

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14
Q

What are the clinical features of male hypogonadism?

A

Loss of libido

Impotence

Small testes

Decreased muscle bulk

Osteoporosis

DUE TO LOW TESTOSTERONE

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15
Q

What is libido?

A

Sexual interest/desire

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16
Q

What is impotence?

A

Inability in a man to achieve an erection

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17
Q

What are the cause of male hypogonadism?

A

HYPOTHALAMIC-PITUITARY DISEASE

  • hypopituitarism
  • Kallman’s syndrome
  • illness/underweight

PRIMARY GONADAL DISEASE

  • congenital (e.g. Klinefelter’s Syndrome XXY)
  • acquired (e.g. testicular torsion, chemotherapy)

HYPERPROLACTINAEMIA

ANDROGEN RECEPTOR DEFICIENCY

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18
Q

What is anosmia?

A

The loss of the sense of smell, either total or partial

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19
Q

What is Kallman’s Syndrome?

A

A condition characterized by delayed or absent puberty and an impaired sense of smell.

A form of hypogonadotropic hypogonadism

It is a condition resulting from a lack of production of certain hormones that direct sexual development.

Anosmia and low GnRH

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20
Q

What does anosmia occur in Kallman’s Syndrome?

A

In Kallman’s, there is low GnRH

GnRH neurones start development in the olfactory placed of the back of the brain

They then migrate forward through development, alongside the neurones for smell

If they fail to migrate forward properly, as in Kallman’s, you have a lack of GnRH causing infertility, pubertal failure and lack of smell

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21
Q

What are the signs and symptoms of Kallman’s Syndrome?

A

Stature low-normal

Pubertal failure

Lack of smell

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22
Q

Why does being underweight cause hypogonadism?

A

The result of lectin

Lectin is secrete by white fat tissue

Low lectin = switches off GnRH neurones

Makes biological sense as you wouldn’t want children being born if food is scarce

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23
Q

How do you investigate potential male hypogonadism?

A

LH/FSH/Testosterone

  • If all low –> MRI of the Pituitary
  • If LH/FSH high & Testosterone low –> potential gonad problem

Prolactin

Sperm Count

Chromosomal Analysis
- Such as for Klinefelter’s Syndrome (XXY)

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24
Q

What is azoospermia?

A

Absence of sperm in ejaculate

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25
What is oligospermia?
Reduced numbers of sperm in ejaculate
26
What can be done to help fertility for a couple in which the male suffers from oligospermia?
Intra Cytoplasmic Sperm Injection (ICSI) Take sperm and inject it directly into oocyte in an IVF setting
27
How is male hypogonadism treated?
All Patients - replacement testosterone Fertility [if hypo/pit disease] - s.c. gonadotrophins (LH and FSH) - to stimulate spermatogenesis Hyperprolactinaemia - dopamine agonist
28
When treating male hypogonadism, in what situation what s.c. gonadotrophins not help to improve fertility?
For patients with azoospermia as this is a problem of the testes themselves, not of the hypothalamus or the pituitary
29
What are endogenous site of androgen production?
Interstitial Leidig cells of the testes Adrenal Cortex (males and females) Ovaries Placenta Tumours
30
What are the main actions of testosterone?
Development of the male genital trait Maintains fertility in adulthood Control of secondary sexual characteristics Anabolic effects (muscle, bone)
31
How much circulating testosterone is protein bound?
98% is protein bound
32
What occurs in tissue-specific processing of testosterone?
E.G. MUSCLE AND BONE - want testosterone to have androgenic action - 5α -reductase - converted to DIT - acts via the androgen receptor (AR) E.G. BRAIN AND ADIPOSE TISSUE - aromatase - 17β-oestradiol - acts via oestrogen receptor (ER)
33
What does DIT stand for?
Dihydrotestosterone
34
How do the DIT and E↓2 carry out their mechanism of action?
Via nuclear receptors
35
What is the shorthand form of the 17β-oestradiol?
E↓2 (little 2)
36
What does testosterone do in male adulthood?
Increases: - lean body mass - muscle size and strength - bone formation and bone mass (young men) - libido and potency
37
Can testosterone restore fertility in men?
No This requires treatment with gonadotrophin to restore normal spermatogenesis
38
What are the three main infertility disorders in female?
Amenorrhea Polycystic Ovarian Syndrome (PCOS) Hyperprolactinaemia
39
Define amenorrhea
Absence of periods
40
What is primary amenorrhea?
Failure to begin spontaneous menstruation by age 16 years
41
What is secondary amenorrhea?
Absence of menstruation for 3 months in a woman who has previously had cycles
42
What is oligomenorrhoea?
Irregular long cycles
43
What is a major potential difference in causes for primary and secondary amenorrhea?
As women with primary amenorrhea have had no previous periods, this could more likely be a congenital problem than secondary amenorrhea.
44
What are the causes of amenorrhea?
Pregnancy/Lactation Ovarian Failure Gonadotrophin Failure Hyperprolactinaemia Androgen Excess (Gonadal Tumour)
45
Why does lactation cause amenorrhea?
High prolactin levels Suppresses reproductive axis via kisspeptin receptors
46
What is premature ovarian failure?
Also known as primary ovarian insufficiency It is a loss of normal function of your ovaries before age 40. If your ovaries fail, they don't produce normal amounts of the hormone estrogen or release eggs regularly.
47
What occurs that causes menopause to happen?
The set number of eggs that a woman is born with run out
48
What are the signs and symptoms of Turners Syndrome (45 XO) in women?
Short stature Cubitus valgus (wide carrying angle when resting arms) Gonadal dysgenesis
49
How many live female births are affected by Turners Syndrome?
1 in 5000
50
What can cause Ovarian Failure?
Premature ovarian failure Ovariectomy/chemotherapy Ovarian dysgenesis (Turners 45 XO, lacking one chromosome)
51
What can cause Gonadotrophin Failure?
Hypo/Pit Disease Kallmann's Syndrome (anosmia, low GnRH) Low BMI Post-Pill Amenorrhea
52
How is post-pill amenorrhea treated?
Patient comes off the pill and period typically returns within 12 months
53
How do healthcare professionals attempt to prevent post-pill amenorrhea?
Advise patients to change their pill every 4 years
54
How would you clinically investigate and diagnose someone with amenorrhea?
Pregnancy Test LH/FSH/Oestradiol Day 21 Progesterone - see if ovulation is occurring - progesterone increases during ovulation Prolactin, Thyroid Function Tests Androgens - testosterone - androstenedione - DHEAS Chromosomal analysis - Turner's 45 XO Ultrasound Scan - Ovaries/Uterus
55
How do you treat amenorrhea?
Treat the cause - e.g. low weight Primary Ovarian Failure - Essentially infertile - HRT Hypothalamic/Pit Disease - HRT for oestrogen replacement - Gonadotrophins as part of IVF treatment for fertility
56
What is the incidence of PCOS?
1 in 12 women of reproductive age
57
What conditions does PCOS increase the risk of a woman getting?
Associated with increased cardiovascular risk and insulin resistance (>diabetes)
58
How do you diagnose PCOS?
Patient must have 2 of the following: - polycystic ovaries on USS - oligo-/anovulation - clinical/biochemical androgen excess (male hirsute pattern of growth)
59
Define oligoovulation and anovulation
Oligoovulation = infrequent or irregular ovulation Anovulation = ovulation does not take place during menstrual cycles
60
What are the clinical features of PCOS?
Hirsutism Menstrual Cyle Disturbance Increased BMI
61
Name 3 treatments used for PCOS
Metformin Clomiphene Gonadotrophin Therapy as part of IVF treatment
62
Why is Clomiphene used to treat PCOS?
Anti-Oestrogenic in the hypothalamo-pituitary axis Binds to oestrogen receptors in the hypothalamus This blocks the normal negative feedback Resulting in secretion of GnRH and gonadotrophins
63
What is the main problem with IVF?
It is very expensive
64
In what genders can hyperprolactinaemia occur?
All genders
65
How is the normal secretion of prolactin controlled?
- Hypothalamus secretes dopamine - Dopamine inhibits pituitary (inhibitory) - Anterior pituitary doesn't release prolactin However, TRH has a small stimulatory action on the anterior pituitary to release prolactin but this is much smaller than dopamine's inhibitory effect
66
What are the effects of Prolactin in the body?
Involved in breast milk expression and secretion, therefore you only really need it when breastfeeding. In high amounts, prolactin also switches off GnRH pulsatility In high amounts, prolactin also reduces LH actions on ovary/testes. The biological reasoning for this is that when you're breastfeeding, it tries to decrease fertility so a woman does not get pregnant again straight away
67
How is GnRH released?
GnRH released in pulsatile manner every 90 minutes on average
68
What are the causes for hyperprolactinaemia?
Dopamine Antagonist Drugs Prolactinoma Stalk Compression due to pituitary adenoma PCOS Hypothyroidism Oestrogens (OCP), Pregnancy, Lactation Idiopathic
69
Name types of Dopamine Antagonist Drugs
- anti-emetics (metoclopramide) | - anti-psychotics (phenothiazines)
70
What is a prolactinoma?
Benign tumour of the pituitary gland releasing too much prolactin
71
How does stalk compression of the pituitary due to a pituitary adenoma cause hyperprolactinaemia?
Tumour compresses pituitary stalk Dopamine not release down hypothalamo-pituitary tract Therefore, prolactin release is not effectively inhibited by dopamine High prolactin release from pituitary
72
What are the clinical features of hyperprolactinaemia?
Galactorrhoea Reduced GnRH secretion/LH action - leading to hypogonadism - loss of periods Prolactinoma - headache - visual field defect
73
How is hyperprolactinaemia treated?
Treat the cause - e.g. stop dopamine antagonist drugs Dopamine agonist Prolactinoma - dopamine agonist therapy - pituitary surgery rarely needed
74
Name 2 examples of dopamine agonist drugs
Bromocriptine Cabergoline
75
What are the benefits of dopamine agonist therapy for a patient with a prolactinoma?
Can shrink the tumour Can switch off the prolactin secretion
76
What would the blood results show with regards to gonadotrophins and androgens from a male who has had bilateral orchidectomy?
High LH High FSH Low Testosterone
77
What would the blood results show regarding gonadotrophins and oestrogen in a young woman who presents with secondary amenorrhea and galactorrhea? [She also has prolactin of 4500, which is high]
Low LH Low FSH Low Oestradiol (High prolactin switches of GnRH pulsatility, decreasing gonadotrophins and sex hormones)

Yr 2 LCRS - Endo (28 decks)

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