Endocrine Infertility

Question 1

Which cells within the testes does LH stimulate and what does it make these cells produce?

Answer 1

Leydig Cells –> they are stimulated to produce testosterone

Question 2

Which cells within the testes does FSH stimulate and what does it makes these cells produce?

Answer 2

Sertoli cells (in the seminiferous tuules) –> they are stimulated to produce sperm and inhibin A and B

Question 3

What does inhibin inhibit?

Answer 3

Pituitary FSH secretion

Question 4

What are the three phases of the menstrual cycle?

Answer 4

Follicular Phase
Ovulation
Luteal Phase

Question 5

What does LH stimulate in the ovaries?

Answer 5

Oestradiol and progesterone production

Question 6

What does FSH stimulate in the ovaries?

Answer 6

Follicular development and inhibin production

Question 7

What effect does oestrogen have on the HPG axis in the follicular phase of the menstrual cycle?

Answer 7

It has a negative feedback effect – inhibits FSH and LH

Question 8

What does the leading follicle develop into by around day 10?

Answer 8

Graffian Follicle

Question 9

Once oestrogen reaches a certain level it switches to positive feedback. How does it do this?

Answer 9

It increases the GnRH secretion

It increases LH sensitivity to GnRH

Question 10

Define infertility.

Answer 10

Inability to conceive after 1 year of regular unprotected sex

Question 11

What is primary gonadal failure and what effects does it have on the HPG axis?

Answer 11

It is a problem with the gonads
The testes/ovaries don’t produce enough testosterone/oestrogen so there is no negative feedback on the HPG axis meaning that you get high GnRH, high LH and high FSH.

Question 12

Describe the levels of the different hormones in the HPG axis in the case of hypothalamic/pituitary disease causing infertility.

Answer 12

Low GnRH
Low FSH
Low LH

Question 13

State some of the clinical features of male hypogonadism.

Answer 13

Loss of libido 
Impotence  
Small testes  
Decreased muscle bulk 
Osteoporosis (testosterone has anabolic action in the bone)

Question 14

State 5 causes of male hypogonadism.

Answer 14

Hypopituitarism 
Kallmann’s Syndrome (anosmia + low GnRH) 
Illness/underweight 
Hyperprolactinaemia 
Androgen receptor deficiency (RARE)

Question 15

State some congenital and acquired causes of primary gonadal disease.

Answer 15

Congenital: Klinefelter’s Syndrome (XXY)
Acquired: Testicular torsion, chemotherapy

Question 16

What are the main investigations for male hypogonadism?

Answer 16

LH, FSH and testosterone (if all are low –> MRI to check pituitary problem)
Prolactin
Sperm count (azoospermia – absence of sperm in ejaculate; oligospermia – reduced number of sperm in ejaculate)
Chromosomal analysis (check for Klinefelter’s)

Question 17

What is given to all patients with hypogonadism?

Answer 17

Testosterone to increase muscle bulk and protect against osteoporosis

Question 18

How do you restore fertility in someone with hypothalamic/pituitary disease?

Answer 18

Subcutaneous gonadotrophin injections – stimulates testosterone release

Question 19

What is the treatment for hyperprolactinaemia?

Answer 19

Dopamine agonists – bromocriptine and cabergoline  
Pituitary surgery (though this is rarely used because medicine normally works well)

Question 20

State some endogenous sites of production of androgens.

Answer 20

Interstitial leydig cells in the testes  
Adrenal cortex
Ovaries  
Placenta  
Tumours

Question 21

What are the main actions of testosterone?

Answer 21

Development of the male genital tract 
Maintains fertility in adulthood  
Control of secondary sexual characteristics 
Anabolic effects (muscle, bone)

Question 22

Testosterone is heavily plasma protein bound and it can be converted to other hormones in various tissues. State two products that testosterone can be converted to and the enzymes responsible for these conversions.

Answer 22

Converted by 5-alpha-reductase to dihydrotestosterone (DHT), which acts on androgen receptors
Converted by aromatase to 17-beta-oestradiol, which acts on oestrogen receptors

Question 23

What type of receptors does DHT and E2 act on?

Answer 23

Nuclear receptors

Question 24

What are the clinical uses of testosterone?

Answer 24

Lean body mass 
Muscle size and strength 
Bone formation and bone mass  
Libido and potency  
NOTE: it does NOT restore fertility

Question 25

What is the difference between primary and secondary amenorrhoea?

Answer 25

Primary Amenorrhoea = failure to develop spontaneous menstruationby the age of 16 years
Secondary Amenorrhoea = absence of menstruation for 3 months in a woman who has previously had cycles

Question 26

What is oligomenorrhoea?

Answer 26

Irregularly long cycles

Question 27

List some causes of amenorrhoea.

Answer 27

Pregnancy 
Lactation 
Ovarian failure: 
 Premature ovarian insufficiency
 Oophorectomy 
 Chemotherapy
 Ovarian dysgenesis (Turner’s Syndrome (45 X))
Hypothalamic/pituitary disease 
Kallmann’s syndrome  
Low BMI 
Post-pill amenorrhoea (if you use the pill for a long time and then go off it, it could take a while for the periods to return) 
Hyperprolactinaemia 
Androgen excess (gonadal tumour)

Question 28

State some features of Turner’s syndrome.

Answer 28

Short statue
Cubitus valgus (forearm is angled away from the body to a greater degree than normal when fully extended)
Gonadal dysgenesis

Question 29

State some investigations for amenorrhoea.

Answer 29

Pregnancy test
LH, FSH and Oestradiol
Day 21 Progesterone (this should be high (showing that you’re ovulating) because progesterone rises in the second half of the menstrual cycle)
Prolactin
Thyroid function test (both hyper- and hypothyroidism can cause problems with the menstrual cycle)
Androgens (testosterone, androstenedione, DHEAS)
Chromosomal analysis

Question 30

What are the implications on health of polycystic ovarian syndrome (PCOS)?

Answer 30

Increased cardiovascular risk  
Insulin resistance (diabetes)

Question 31

What are the criteria for diagnosing PCOS?

Answer 31

They must have at least 2 of the following:
 Polycystic ovaries on ultrasound scan
 Clinical/biochemical signs of androgen excess
 Oligoovulation/anovulation

Question 32

What are the clinical features of PCOS?

Answer 32

Hirsuitism
Menstrual irregularities
Increased BMI

Question 33

Describe the treatment for PCOS.

Answer 33

METFORMIN – insulin sensitiser
CLOMIFENE – anti-oestrogenic effects in the hypothalamo-pituitary axis – binds to oestrogen receptors in the hypothalamus thereby blocking the negative feedback –> increased GnRH and gonadotrophin secretion
GONADOTROPHIN THERAPY as part of IVF treatment

Question 34

What hypothalamic hormone has a stimulatory effect on prolactinrelease?

Answer 34

Thyrotrophin releasing hormone (TRH)

Question 35

What effect does hyperprolactinaemia have on the HPG axis?

Answer 35

It reduces GnRH pulsatility so that it is released basally all the time rather than in regular pulses
It will switch off gonadal function via LH actions on the ovaries and testes

Question 36

State some causes of hyperprolactinaemia.

Answer 36

Dopamine antagonists (anti-emetics and anti-psychotics)  
Prolactinoma 
Stalk compression due to pituitary adenoma (so dopamine can’t get to adenohypophysis) 
PCOS 
Hypothyroidism 
Oestrogens (OCP)
Pregnancy 
Lactation  
Idiopathic

Question 37

What are the clinical features of hyperprolactinaemia?

Answer 37

Galactorrhoea 
Reduced GnRH and gonadotrophin secretion --> HYPOGONADISM 
Prolactinoma: 
 Visual field defect 
 Headache