9 - endocrine infertility Flashcards
What is produced from the hypothalamus that stimulates the release of FSH and LH from the pituitary?
GnRH
Which cells within the testes does LH stimulate and what does it make these cells produce?
Leydig Cells
are stimulated to produce testosterone
Which cells within the testes does FSH stimulate and what does it makes these cells produce?
Sertoli cells (in the seminiferous tubules) are stimulated to produce sperm and inhibin A and B
What is the role of testosterone in the male hypothalamus-pituitary-gonadal axis?
responsible for secondary sexual characteristics and aids spermatogenesis
has a negative feedback on the hypothalamus and pituitary
What does inhibin inhibit?
Pituitary FSH secretion
What are the three phases of the menstrual cycle?
Follicular Phase
Ovulation
Luteal Phase
What does LH stimulate in the ovaries?
Oestradiol and progesterone production
What does FSH stimulate in the ovaries?
Follicular development and inhibin production
What effect does oestrogen have on the HPG axis in the follicular phase of the menstrual cycle?
It has a negative feedback effect – inhibits FSH and LH
What does the leading follicle develop into by around day 10?
Graffian Follicle
What effect does oestrogen have on the HPG axis in the follicular phase of the menstrual cycle?
It has a negative feedback effect – inhibits FSH and LH
Once oestrogen reaches a certain level it switches to positive feedback. How does it do this?
What affect does this have on other hormones and why is this necessary?
It increases the GnRH secretion
It increases LH sensitivity to GnRH
Leads to mid-cycle LH surge which is needed for egg maturation and ovulation
Define primary gonadal failure
defect/failure of the gonads (testes/ovaries)
testes/ovaries don’t produce enough testosterone/
If you did a blood test on someone with primary gonadal failure, what would the levels of hormones in the blood be?
high GnRH
high FSH and LH
(testes/ovaries are not producing testosterone/oestrogen so there is no negative feedback)
Define infertility.
Inability to conceive after 1 year of regular unprotected sex
Describe the levels of the different hormones in the HPG axis in the case of hypothalamic/pituitary disease causing infertility.
(is this secondary/tertiary hypogonadism)
Low GnRH
Low FSH
Low LH
(low oestrodiol and testosterone)
State some of the clinical features of male hypogonadism.
Loss of libido Impotence Small testes Decreased muscle bulk Osteoporosis (testosterone has anabolic action in the bone)
State 5 causes of male hypogonadism
- Hypopituitarism
- Kallmann’s Syndrome (anosmia + low GnRH)
- Primary Gonadal Disease
- Illness/underweight
- Hyperprolactinaemia
- Androgen receptor deficiency (RARE)
How can illness/being underweight cause hypogonadism (males)?
due to the low levels of leptin
State some congenital and acquired causes of primary gonadal disease.
Congenital: Klinefelter’s Syndrome (XXY)
Acquired: Testicular torsion, chemotherapy
What are the main investigations for male hypogonadism?
- LH, FSH and testosterone (if all are low -> MRI to check pituitary problem)
- Prolactin
- Sperm count
- Chromosomal analysis (check for Klinefelter’s)
Define azoospermia and oligospermia in reference to sperm count
azoospermia – absence of sperm in ejaculate; oligospermia – reduced number of sperm in ejaculate
What is the treatment for male hypogonadism?
- replacement testosterone is given to all patients (to increase muscle bulk and protect against osteoporosis)
- gonadotrophins (SC injections) - for fertility (in hypothalamic/pituitary disease)
- dopamine agonist (for hyperprolactinaemia)
(included in Q23)
What is given to all patients with hypogonadism?
Testosterone to increase muscle bulk and protect against osteoporosis
(included in Q23)
How do you restore fertility in someone with hypothalamic/pituitary disease?
Subcutaneous gonadotrophin injections – stimulates testosterone release
(included in Q23)
What is the treatment for hyperprolactinaemia (causing hypogonadism)?
Dopamine agonists – bromocriptine and cabergoline Pituitary surgery (though this is rarely used because medicine normally works well)
State some endogenous sites of production of androgens.
Interstitial leydig cells in the testes Adrenal cortex Ovaries Placenta Tumours
What are the main actions of testosterone?
- Development of the male genital tract
- Maintains fertility in adulthood
- Control of secondary sexual characteristics
- Anabolic effects (muscle, bone)
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.
Converted by 5α-reductase to dihydrotestosterone (DHT), which acts on androgen receptors
Converted by aromatase to 17β-oestradiol, which acts on oestrogen receptors
What type of receptors does DHT and E2 act on?
Nuclear receptors
What are the clinical uses of testosterone?
Lean body mass Muscle size and strength Bone formation and bone mass Libido and potency NOTE: it does NOT restore fertility
What is the difference between primary and secondary amenorrhoea?
Primary Amenorrhoea = failure to develop spontaneous menstruation by the age of 16 years
Secondary Amenorrhoea = absence of menstruation for 3 months in a woman who has previously had cycles
What is oligomenorrhoea?
Irregularly long cycles
List the causes of amenorrhoea.
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)
State some features of Turner’s syndrome.
Short stature
Cubitus valgus (forearm is angled away from the body to a greater degree than normal when fully extended)
Gonadal dysgenesis
State some investigations for amenorrhoea.
- 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
- ultrasound scan of ovaries/uterus (for PCOS)
What is the treatment of amenhorrhoea?
- treat the cause (e.g. low weight)
- for primary ovarian failure give HRT
- for hypothalamic/pituitary disease:
- —-> HRT for oestrogen replacement
- —-> gonadtrophins for fertility
What are the implications on health of polycystic ovarian syndrome (PCOS)?
Increased cardiovascular risk Insulin resistance (diabetes)
What are the criteria for diagnosing PCOS?
They must have at least 2 of the following:
• Polycystic ovaries on ultrasound scan
• Clinical/biochemical signs of androgen excess
• Oligoovulation/anovulation (not ovulating properly)
What are the clinical features of PCOS?
Hirsuitism
Menstrual irregularities
Increased BMI
Describe the treatment for PCOS.
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
What hypothalamic hormone has a stimulatory effect on prolactin release?
Thyrotrophin releasing hormone (TRH)
NOTE: its effects are much weaker
What effect does hyperprolactinaemia have on the HPG axis?
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
State some causes of hyperprolactinaemia.
- Dopamine antagonists (anti-emetics and anti-psychotics)
- Prolactinoma
- Stalk compression due to pituitary adenoma (dopamine can’t get to adenohypophysis)
(milder causes:)
- PCOS
- Hypothyroidism
- Oestrogens (OCP)
- Pregnancy
- Lactation
- Idiopathic
What are the clinical features of hyperprolactinaemia?
- Galactorrhoea
- Reduced GnRH and gonadotrophin secretion ->HYPOGONADISM
- Prolactinoma:
• Visual field defect
• Headache
