9. Endocrine Infertility Flashcards
1
Q
Outline the male hypothalamo-pituitary-gonadal axis
A
- GnRH pulses from hypothalamus
- Stimulation of LH + FSH release from pituitary
- LH stimulates leydig cells to produce testosterone
- FSH stimulates sertoli cells in seminiferous tubules to produce sperm and inhibin A + B
- Inhibin has negative feedback on pituitary FSH secretion
2
Q
What are the phases of the menstrual cycle?
A
- Follicular phase
- Ovulation
- Luteal phase
3
Q
Describe the follicular phase
A
- GnRH pulses stimulate LH + FSH
- LH stimulates production of oestradiol and progesterone in the ovaries
- FSH stimulates follicular development and inhibin
- Around day 10, leading follicle => Graffian Follicle
- Oestrogen initially has negative feedback on LH + FSH secretion
4
Q
Describe ovulation and the luteal phase
A
- Once oestrogen reaches a certain level, it switches from negative to positive feedback
- Increases GnRH release and LH sensitivity to GnRH
- Mid-cycle LH surge
- Triggers ovulation from the leading follicle
- Progestrone rises
- If no implantation - endometrium is shed
5
Q
Define infertility, and the proportion of couples it can affect
A
- Inability to conceive after 1 year of regular unprotected sex
- 1/6 couples can be affected
- Abnormalities - 30% males, 45% females, 25% unknown
6
Q
What does primary gonadal failure lead to?
A
- Testes/ovaries not producing testosterone/oestrogen
- No negative feedback on HPG axis
- High GnRH and high LH + FSH
7
Q
What is hypothalamic/pituitary disease?
A
- Secondary gonadal failure/hypopituitarism
- Inability of pituitary to produce FSH + LH - low levels
- Therefore, low oestradiol/testosterone
8
Q
What are the clinical features of male hypogonadism?
A
- Loss of libido
- Impotence
- Small testes
- Decreased muscle bulk
- Osteoporosis (testosterone has anabolic action in the bone)
9
Q
What are the causes of hypothalamic-pituitary disease?
A
- Hypopituitarism - secondary gonadal failure
- Kallmann Syndrome - anosmia and low GnRH, due to failure of GnRH and olfactory neurones to migrate from back of brain in development
- Illness/underweight - low levels of leptin
10
Q
Give congenital and acquired causes of primary gonadal disease
A
- Congenital: Klinefelters Syndrome (XXY)
* Acquired: Testicular torsion, chemotherapy
11
Q
What effect can hyperprolactinaemia have on the gonads?
A
Inhibit gonadal function
12
Q
How else can low testosterone levels/insensitivity be referred to and why?
A
- Hypoandrogenism
- Testosterone = androgen
- Androgen receptor deficiency is a rare congenital cause of hypogonadism
13
Q
How do you investigate male hypogonadism?
A
- LH, FSH and testosterone - if low, MRI of pituitary
- Prolactin
- Sperm count: azoospermia = absence, oligospermia = reduced numbers
- Chromosomal analysis
14
Q
What is an ICSI?
A
- Intracytoplasmic sperm injections
* Combats infertility in someone with oligospermia
15
Q
How can male hypogonadism be treated?
A
- All patients: replacement testosterone for all patients
- Hypothalamic/pituitary disease: subcutaneous gonadotrophin injections, inducing spermatogenesis for fertility
- Hyperprolactinaemia: dopamine agonist, (main influence) negative effect on prolactin release
16
Q
What are the endogenous sites of androgen production?
A
- Adrenal cortex
- Interstitial Leydig cells
- Ovaries
- Placenta
- Tumours
17
Q
What are the main actions of testosterone?
A
- Development of male genital tract
- Maintains fertility in adulthood
- Control of secondary sexual characteristics
- Anabolic effects
18
Q
How much of testosterone is protein bound
A
98%
19
Q
How is testosterone altered to act on androgen receptors?
A
- 5 α-reductase converts it into dihydrotestosterone (DHT)
* Goes into nucleus - nuclear receptors
20
Q
How is testosterone altered to act on oestrogen receptors?
A
- Aromatase converts it into 17β-oestradiol (E2)
* Goes into nucleus - nuclear receptors
21
Q
What are the clinical uses of testosterone?
A
• Lean body mass • Muscle size and strength • Bone formation and bone mass • Libido and potency (• will not restore fertility)
22
Q
What is primary amenorrhoea?
A
Failure to develop spontaneous menstruation by age 16
23
Q
What is secondary amenorrhoea?
A
- Absence of menstruation for 3 months in a woman who has previously had cycles
- Probably not congenital
24
Q
What is oligomenorrhoea?
A
Irregular long cycles
25
What are the causes of amenorrhoea?
```
• Pregnancy
• Lactation
• Ovarian failure
- premature ovarian insufficiency
- oophorectomy/ovariectomy
- chemotherapy
- ovarian dysgenesis - Turner's syndrome
• Gonadotrophin failure (can also be caused by the pill)
```
26
What are some of the features of Turner's syndrome?
* Short stature
* Cubitus Valgus (angled forearm)
* Gonadal dysgenesis
27
How can amenorrhoea be investigated?
* Pregnancy test
* LH, FSH and oestradiol
* Day 21 progesterone - rises in second half of menstrual cycle
* Prolactin
* Thyroid function test - hyper/hypothyroidism can cause problems
* Androgens
* Chromosomal analysis
* Ultrasound
28
How can amenorrhoea be treated?
```
• Treat the cause
• Primary ovarian failure - hormone replacement therapy (HRT)
• Hypothalamic/pituitary disease
- HRT for oestrogen replacements
- Gonadotrophins for fertility
```
29
Who gets polycystic ovarian syndrome (PCOS) and what is it associated with?
* 1/12 women of reproductive age
| * Associated with increased cardiovascular risk and insulin resistance (diabetes)
30
What are the criteria to diagnose PCOS?
• 2 of the following:
- polycystic ovaries on ultrasound
- oligoovulation/anovulation
- androgen excess
31
What are the clinical features of PCOS?
* Hirsuitism
* Menstrual cycle disturbance
* Increased BMI
32
How is PCOS treated (fertility)?
• Metformin - insulin sensitiser
• Clomiphene
- anti-oestrogenic effect in hypothalamo-pituitary axis
- Binds to oestrogen receptors in hypothalamus, blocking negative feedback
- Increase in GnRH and gonadotrophin secretion
• Gonadotrophin therapy
33
What happens if prolactin secretion is dysregulated?
* Gonadal function switched off via LH actions on the ovaries and testes
* Reduced GnRH pulsatility - released all the time rather than in pulses
34
What are the causes of hyperprolactinaemia?
* Dopamine antagonists: anti-emetics and anti-psychotics (more likely as it's used long term)
* Prolactinoma
* Stalk compression due to adenoma - dopamine can't get through
* PCOS
* Hypothydroidism
* Oestrogens (pill), pregnancy, lactation
* Idiopathic
35
What are the clinical features of hyperprolactinaemia?
* Galactorrhoea
* Hypogonadism - due to reduced GnRH secretion/LH action
* Prolactinoma - headache, visual field defect
36
How can hyperprolactinaemia be treated?
* Treat the cause e.g. stop taking drugs causing the problem if possible, surgery
* Dopamine agonists - bromocriptine, cabergoline (also decreases tumour if prolactinoma)
