Endocrine infertility Flashcards
21.10.2019 (50 cards)
1
Q
How long is the female menstrual cycle?
A
- textbook: 28d
- reality: 25-35d
2
Q
Normal hypothalamo-pituitary-gonadal axis in males
A
GnRH ++ LH, FSH ++Testosterone
negative feedback on H and AP by inhibin
3
Q
What are the phases of the menstrual cycle?
A
- follicular phase
- ovulation
- luteal phase
4
Q
Describe, in detail, how the menstrual cycle works
A
LAST YEARS FLASHCARD
5
Q
What are the possible outcomes in the luteal phase?
A
- if implantation occurs -> pregnancy
- if implantation does not occur - endometrium I shed (menstruation)
6
Q
What is infertility?
A
- inability to concieve after 1 year of regular unprotected sex
7
Q
How common is infertility?
A
1:6 couples
8
Q
What abnormalities cause infertility?
A
- in males (30%)
- or females (45%)
- or unknown (25%)
9
Q
Primary gonadal failure
A
- there is stimulation by the hypothalamus / AP
- gonads themselves don’t make oestradiol / testosterone
10
Q
Secondary gonadal failure
A
- due to hypothalamus / pituitary disease
- low LH and FSH
- not enough stimulation of the gonads -> low estradiol / testosterone
11
Q
Clinical features of male hypogonadism
A
- Loss of libido = sexual interest / desire
- Impotence
- Small testes
- Decrease muscle bulk
- osteoporosis
12
Q
Why does male hypogonadism cause osteoporosis?
A
- is it because Testosterone is aromatised to oestrogen and oestrogen has bone preserving qualities?
- is it because of the anabolic effects that testosterone has on muscle and bone?
13
Q
What are causes of male hypogonadism?
A
- hypothalamic-pituitary disease (hypopituitarism, Kallmans syndrome, Illness/underwight (linked to leptin))
- primary gonadal disease (congenital: Klinefelters syndrome XXY; acquired: testicular torsion, chemotherapy)
- Hyperprolactinaemia
- androgen receptor deficiency
14
Q
Kallmanns syndrome
A
- anosmia
- low GnRH
=> delayed or absent puberty, impaired sense of smell
15
Q
Why is anosmia common with low GnRH?
A
This is due to the fact that during embryonal development GnRH neurones and the olfactory nerves travel together
16
Q
Investigations in male hypogonadism
A
- LH, FSH, testosterone -> if all low do a pituitary MRI
- Prolactin
- Sperm count
- chromosomal analysis (Klinefelters XXY)
17
Q
Azoospermia
A
absence of sperm in ejaculate
18
Q
Oligospermia
A
reduced numbers of sperm in ejaculate
19
Q
How can you treat male hypogonadism?
A
- replacement testosterone for all patients
- For fertility: if hypo / pit disease -> s.c. gonadotrophins (LH & FSH)
- Hyperprolactinaemia - dopamine agonist
20
Q
Endogenous sites of production of androgens
A
- interstitial Leydig cells of the testes
- adrenal cortex (males and females)
- ovaries
- placenta
- tumours
21
Q
What are the main actions of testosterone?
A
- development of the male genital tract
- Maintains fertility in adulthood
- Control of secondary sexual characteristics
- Anabolic effects (muscle, bone)
22
Q
How much of circulating testosterone is protein bound?
A
98%
23
Q
What can testosterone be turned into?
A
- reduction: Dihydrotestosterone (DHT), more potent, acts via the androgen receptor
- aromatisation: 17-beta-oestradiol (E2), acts via the oestrogen Receptor (ER) e.g. brain and adipose tissue
24
Q
Enzyme: Testosterone -> DHT
A
5-alpha reductase
25
Enzyme: Testosterone -> 17-beta-oestradiol
aromatase
26
Mechanism of action of DHT / E2
via nuclear receptors
27
Clinical uses of testosterone
- in adulthood will increase
- lean body mass
- muscle size and strength
- bone formation and bone mass (in young men)
- libido and potency
It will not restore fertility, which requires treatment with gonadotrophins to restore normal spermatogenesis!!
28
What are 3 common disorders in females that cause infertility?
1. Amenorrhea
2. PCOS
3. Hyperprolactinaemia
29
Amenorrhoea
= absence of periods
30
Primary amenorrhoea
failure to begin spontaneous menstruation by age 16 years
31
Secondary Amenorrhoea
absence of menstruation for 3 months in a woman who has previously had cycles
32
Oligomenorrhoea
irregular long cycles
33
Causes of Amenorrhoea
- pregnancy / lactation
- ovarian failure (premature ovarian failure, ovariectomy, chemotherapy, ovarian dysgenesis in Turners Syndrome 45X
- Gonadotrophin failure (hypo/pit disease, kallmann's syndrome, low BMI, post pill amenorrhoea)
- hyperprolactinaemia
- androgen excess: gonadal tumor
34
How common is Turners syndrome?
1:5000 live female births
35
Investigations for Amenorrhoea
- Pregnancy test
- LH, FSH, oestradiol
- Day 21 progesterone (18,21,24 due to variation)
- Prolactin
- thyroid function tests
- androgens (testosterone, androstenedione, DHEAS)
- chromosomal analysis (Turners 45X)
- Ultrasound scan of ovaries/uterus
36
Treatment of amenorrhoea
- Treat the cause (eg low weight)
- Primary ovarian failure – infertile, HRT
- Hypothalamic / pituitary disease
HRT for oestrogen replacement
Fertility: Gonadotrophins
37
PCOS
= polycystic ovarian syndrome
- Associated with increased cardiovascular risk and insulin resistance (>diabetes)
38
How common is PCOS?
1 in 12 women of reproductive age have it.
39
What are the criteria needed to diagnose PCOS?
- polycystic ovaries on USS
- oligo-/anovulation
- clinical / biochemical androgen excess
40
Clinical feature of PCOS
- Hirsutism
- Menstrual cycle disturbance
- Increased BMI
41
Treatment of PCOS
- metformin (insulin sensitiser)
- clomiphene (anti-oestrogen in the hypo-pit axis)
- gonadotrophin as part of IVF
42
Clomiphene
- anti-oestrogenic in the hypothalamo-pituitary axis
- Bind to oestrogen receptors in the hypothalamus -> block normal negative feedback -> increase in the secretion of GnRH and gonadotrophins
43
Hyperprolactinaemia
- prolactin secreted from the AP has a negative effect on GnRH pulsatility and decreases LH actions on gonads
44
What are causes of Hyperprolactinaemia?
- Dopamine antagonist drugs (Anti-emetics (metoclopramide); Anti-psychotics(phenothiazines))
- Prolactinoma
- Stalk compression due to pituitary adenoma
- PCOS
- Hypothyroidism
- oestrogens (OCP, pregnancy, lactation)
- idiopathic
45
Clinical features if Hyperprolactinaemia
- galactorrhoea
- reduced GnRH secretion / LH action -> hypogonadism
- prolactinoma (headache, visual field defect)
46
How do you treat hyperprolactinaemia?
- Treat the cause – stop drugs
- Dopamine agonist
- Bromocriptine
- Cabergoline
- Prolactinoma
- Dopamine agonist therapy
- Pituitary surgery rarely needed
47
A male presents to endocrine clinic who has had bilateral orchidectomy (removal of testes). What would you expect his blood results to show:
1. Low LH, Low FSH, Low Testosterone
2. Low LH, high FSH, Low Testosterone
3. high LH, high FSH, Low Testosterone
4. high LH, high FSH, high Testosterone
3
48
A young woman presents to endocrine clinic who complains of secondary amenorrhea and galactorrhea. Her GP measured her prolactin at 4500 (high). What would you expect her blood results to show:
1. Low LH, Low FSH, Low oestradiol
2. Low LH, high FSH, Low oestradiol
3. high LH, high FSH, Low oestradiol
4. high LH, high FSH, high oestradiol
1
(this is secondary hypogonadism)
Clinically: however you could also have a normal LH and FSH but on the low end. (inappropriately normal in the context of a low oestradiol)
49
Phenothiazine
- antipsychotic
- dopamine antagonist
- can cause hyperprolactinaemia
50
Which drugs can cause hyperprolactinaemia?
Dopamine antagonist drugs
- Anti-emetics (metoclopramide)
- Anti-psychotics (phenothiazines)
Oestrogen (OCP)
