Endocrine Infertility Flashcards

1
Q

Draw the hypothalamo-pituitary-gonadal axis for males and females

A

See diagram and notes
LH stimulates testosterone production in the leydig cells - testosterone has a negative feedback effect.
FSH stimulates sertoli cells in the seminiferous tubules - sperm and inhibin A. Inhibin also has a negative feedback

Oestradiol initially has a negative feed back on FSH and LH. At high enough concentration it switches to a positive feedback.

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2
Q

What are the main actions of testosterone?

A
Secondary sexual characteristics and spermatogenesis 
Anabolic effect (muscle and bone)
Maintains fertility in adult hood
Development of the male genital tract
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3
Q

What are the phases of the menstrual cycle?

A

28 day menstrual cycle
Follicular phase (same as men; draw HPG axis)
Ovulation (surge in LH -egg maturation and ovulation)
Luteal phase

See notes

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4
Q

Define infertility

A

Inability to conceive after 1 year of regular unprotected sex. Affects 1:6 couples

Caused by abnormalities

1) in males 30%
2) in females 45%
3) unknown 25%

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5
Q

Describe primary gonadal failure

A

The testes/ovaries are defective resulting in low testosterone/oestradiol but a high GnRH and high LH and FSH

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6
Q

Describe hypo/pituitary disease

A

Inability for pituitary gland to produce FSH and LH so low levels of FSH and LH as well as low oestradiol/testosterone.

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7
Q

What are the clinical features of male hypogonadism?

A
Loss of libido
Impotence
Small testes
Decrease muscle bulk
Osteoporosis
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8
Q

What are the causes of male hypogonadism?

A

Hypothalamic-pituitary disease

1) Hypopituitarism
2) Kallmans syndrome (anosmia(lack of smell) & low GnRH)
3) Illness/underweight - mainly due to low levels of leptin which tells your body you are too underweight, not a suitable time to reproduce

Primary gonadal disease

1) Congenital: Klinefelters syndrome (XXY)
2) Acquired: Testicular torsion, chemotherapy

Hyperprolactinaemia

Androgen receptor deficiency - RARE

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9
Q

How do you investigate male hypogonadism?

A

Measure LH, FSH, Testosterone - if all are low they then carry out an MRI for the pituitary to check for pituitary problem

Measure prolactin

Spermcount: Azoospermia and Oligospermia. You look under the microscope to check numbers and motility

Chromosomal analysis (XXY)

See notes - intracytoplasmic sperm injection

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10
Q

Define azoospemia and oligospermia

A
azoospermia = absence of sperm in ejaculate
oligospermia = reduced numbers of sperm in ejaculate
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11
Q

How do you treat male hypogonadism?

A

Replace testosterone - increase their muscle bulk and protect against osteoporosis
For fertility: if hypothalamic/pitutary disease - subcutaneous gonadotrophin injections which induce spermatogenesis
Hyperprolactinaemia - dopamine agonist (cabergoline)

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12
Q

What are the endogenous sites of production of androgens?

A

1) Interstitial leydig cells of the testes
2) Adrenal cortex
3) Ovaries
4) Placenta
5) Tumours

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13
Q

How does testosterone move around in the circulation?

A

Heavily protein bound - 98% protein bound

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14
Q

What can testosterone be converted to and how?

A

Testosterone is converted to dihydrotestosterone (DHT) by 5a-reductase which acts via the androgen receptor
It can also be converted to 17b-oestradiol by aromatase which acts via the oestrogen receptor.
Tissue dependent on what testosterone is converted to.
Both receptors act via nuclear receptors - intracellular. They have to go through the nucleus to have an effect

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15
Q

What are the clinical uses of testosterone?

A
Increase:
Lean body mass
Muscle size and strength
Bone formation and bone mass
Libido and potency

It will not restore fertility

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16
Q

What are the gonadal disorders in females?

A

Amenorrhoea
Polycystic Ovarian Syndrome
Hyperprolactinanaemia

17
Q

Describe ammenorrhoea

A

Abscence of periods
Primary - failure to begin spontaneous menstruation by age 16 years. Suggests congenital problem
Secondary - absence of menstruation for 3 months in a woman who has previously had cycles
Oligomenorrhoea = irregular long cycles

18
Q

What are the causes of ammenorrhoea I (at the ovaries)?

A

Pregnancy
Lactation - high prolactin suppresses periods
Ovarian failure
1) Premature ovarian failure (early menopause)
2) Ovariectomy/chemotherapy
3) Ovarian dysgenesis (turners 45XO) - lacking X chromosome

19
Q

What are the features of Turner’s syndrome?

A

Short stature
Cubitus Valgus (where the forearm is angles away from the body to a greater degree than normal when fully extended)
Gonadal dysgenesis (defective development)
1:5000 live female births

20
Q

What are the causes of ammenorrhea II (hypothalamo-pituitary level)?

A

Gonadotropin failure
1) Hypo/pituitary disease
2) Kallmann’s syndrome (anosmia, Low GnRH)
3) Low BMI
4) Post pill ammenorrhoea - Periods won’t come back for 12 months after stopping it after a long use. Stop using pill every 4 years
Hyperprolactinaemia
Androgen excess: gonadal tumour - easy to diagnose since T in excess. RARE

21
Q

How do you investigate ammenorrhoea?

A
Pregnancy test
LH, FSH, oestradiol
Day 21 progesterone
Prolactin,
Thyroid function tests
Androgens (testosterone, androstenedione, DHEAS)
Chromosomal analysis (Turner's)
Ultrasound scan ovaries/uterus

See notes

22
Q

How do you treat ammenorrhoea?

A
Treat the cause (e.g low weight)
Primary ovarian failure - infertile, HRT
Hypothalamic/pituitary disease
1) HRT for oestrogen replacement
2) Fertility: gondadotrophins (LH and FSH) - part of IVF treatment
23
Q

Describe PCOS

A

Polycystic ovarian syndrome. 1:12 women affected of reproductive age
Associated with increased cardiovascular risk and insulin resistance

24
Q

What are the criteria to diagnose PCOS?

A

Polycystic ovaries on USS
Oligo-/anovulation
Clinical/biochemical androgen excess

25
Q

Clinical features of PCOS?

A

Hirsutism
Menstrual cycle disturbance
Increased BMI

26
Q

How do you treat PCOS?

A

Metformin - Insulin sensitiser used in type II diabetes
Clomiphene - Anti-oestrogen effect in the hypothalamo-pituitary axis. Blocks the oestrogen receptors in the hypothalamus = blocking negative feedback so an increase in GnRH occurs + gonadotrophin secretion.
Used to kick start the HPG axis - short term
Gonadotrophin therapy as part of IVF treatment

27
Q

Draw a diagram showing the control of prolactin secretion

A

See diagram
Dopamine switches of prolactin secretion. Prolactin suppresses GnRH pulsatility + inhibits LH actions on the ovarys/testes

28
Q

What are the causes of hyperprolactinaemia?

A

Dopamine antagonist drugs - anti-emetics (metoclopramide) and anti-psychotics (phenothiazines)
Prolactinoma
Stalk compression due to pituitary adenoma - see diagram

PCOS
Hypothyroidism
Oestrogens (OCP), pregnancy, lactation
Idopathic

29
Q

What are the clinical features of hyperprolactinaemia?

A

Galactorrhoea
Reduced GnRH secretion/LH action&raquo_space; hypogonadism
Prolactinoma - headache, visual field defects

30
Q

How do you treat hyperprolactinaemia?

A

Treat the cause - stop drugs
Dopamine agonist - cabergoline and bromocriptine. They can shrink the tumour as well
Prolactinoma - Dopamine agonist therapy, pituitary surgery rarely needed.