Endocrine Infertility

Question 1

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

Answer 1

Leydig Cells
Produce testosterone (secondary sexual characteristics + aids spermatogenesis)

Question 2

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

Answer 2

Sertoli cells (in seminiferous tubules)
Produce sperm + inhibin A + B

Question 3

What does inhibin inhibit?

Answer 3

Pituitary FSH secretion

Question 4

What are the 3 phases of the menstrual cycle?

Answer 4

Follicular Phase
Ovulation
Luteal Phase

Question 5

What does LH stimulate in the ovaries?

Answer 5

Oestradiol + progesterone production

Question 6

What does FSH stimulate in the ovaries?

Answer 6

Follicular development + 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 + 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 GnRH secretion
It increases LH sensitivity to GnRH
Causes mid cycle LH surge leading to ovulation

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

A problem with the gonads
Testes/ovaries don’t produce enough testosterone/oestrogen so there is no negative feedback on the HPG axis resulting in high GnRH, LH + 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 5 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 6 causes of male hypogonadism.

Answer 14

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

Question 15

State 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 + testosterone (if all low- MRI to check pituitary problem)
Prolactin
Sperm count (azoospermia: absence of sperm in ejaculate; oligospermia: reduced number of sperm in ejaculate)
Chromosomal analysis (Klinefelter’s= XXY)

Question 17

What is given to all patients with hypogonadism?

Answer 17

Testosterone to increase muscle bulk + protect against osteoporosis

Question 18

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

Answer 18

Subcutaneous gonadotrophin injections to stimulate testosterone release

Question 19

What is the treatment for hyperprolactinaemia?

Answer 19

Treat cause- stop drugs
Dopamine agonists – bromocriptine + cabergoline
Pituitary surgery (rarely used because drugs normally works well)

Question 20

State 5 endogenous sites of production of androgens.

Answer 20

Interstitial leydig cells in the testes  
Adrenal cortex
Ovaries  
Placenta  
Tumours

Question 21

What are the 4 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 2 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

Increase lean body mass 
Increase muscle size + strength 
Bone formation + bone mass  
Libido + potency  
(Does NOT restore fertility)

Question 25

What is the difference between primary and secondary amenorrhoea?

Answer 25

Primary= failure to begin spontaneous menstruation by age 16  
Secondary= 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 9 causes of amenorrhoea.

Answer 27

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

Question 28

State 3 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 8 investigations for amenorrhoea.

Answer 29

Pregnancy test
LH, FSH + Oestradiol
Day 21 Progesterone: (high levels indicate ovulation has occurred) measure at day 18, 21 + 24
Prolactin
Thyroid function test (both hyper- + hypothyroidism can cause problems)
Androgens (testosterone, androstenedione, DHEAS)
Chromosomal analysis
Ultrasound scan ovaries/ uterus

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

> 2 of the following:
Polycystic ovaries on ultrasound scan
Clinical/ biochemical signs of androgen excess
Oligoovulation/ anovulation

Question 32

List 3 clinical features of PCOS

Answer 32

Hirsuitism
Menstrual irregularities
Increased BMI

Question 33

Describe the treatment for PCOS.

Answer 33

METFORMIN: insulin sensitiser
CLOMIPHENE: anti-oestrogenic effects in the hypo-pit axis – binds to oestrogen receptors in the hypothalamus thereby blocking negative feedback, increases GnRH + gonadotrophin secretion
GONADOTROPHIN THERAPY as part of IVF treatment

Question 34

What hypothalamic hormone has a stimulatory effect on prolactin release?

Answer 34

Thyrotrophin releasing hormone (TRH)

Question 35

What effect does hyperprolactinaemia have on the HPG axis?

Answer 35

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 + testes

Question 36

State 9 causes of hyperprolactinaemia.

Answer 36

Dopamine antagonists (anti-emetics + 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 3 clinical features of hyperprolactinaemia?

Answer 37

Galactorrhoea
Reduced GnRH + gonadotrophin secretion: HYPOGONADISM
Prolactinoma: Visual field defect + Headache

Question 38

Describe treatment of amenorrhoea

Answer 38

Treat cause (e.g. low weight)
Primary ovarian failure (Infertile, HRT)
Hypothalamic/ pituitary disease (HRT for oestrogen replacement, fertility- gonadotrophins)