Endocrine infertility Flashcards
Testosterone feedback loop diagram
Follicular phase feedback loop diagram
Feedback loop at ovulation diagram.
(oestrogen +ve feedback)
Define infertility.
Inability to conceive after 1 year of regular unprotected sex.
How common is infertility.
1:6 couples
What abnormalities most commonly cause infertility?
Females - 45%
Males - 30%
Unknown - 25%
What hormone levels are seen in primary gonadal failure?
high GnRH, high LH/FSH due to low testosterone/oestrodiol. No -ve feedback
What hormone levels are need in hypo/pituitary disease causing infertility?
Low LH/FSH leading to low testosterone/oestrodiol - failure to stimulate gonads due to pituitary/hypothalamus failiure.
List some clinical features of male hypogonadism?
- Loss of libido = sexual interest / desire
- Impotence
- Small testes
- Decrease muscle bulk
- osteoporosis
List causes of male hypogonadism.
•Hypothalamic-pituitary disease
–Hypopituitarism
–Kallmans syndrome (anosmia & low GnRH)
–Illness / underweight
•Primary gonadal disease
–Congenital: Klinefelters syndrome (XXY)
–Acquired: Testicular torsion, Chemotherapy
- Hyperprolactinaemia
- Androgen receptor deficiency
Give 2 features of Kallman’s syndrome.
Testes originally undescended.
Low stature
What can be investigated to diagnose male hypogonadism?
•LH, FSH, testosterone
–If all low >> MRI pituitary
- Prolactin
- Sperm count
–Azoospermia = absence of sperm in ejaculate
–Oligospermia = reduced numbers of sperm in ejaculate
Chromosomal analysis (Klinefelters XXY).
How can male hypogonadism be treated?
Replacement testosterone.
For fertility (e.g. with pituitary/hypothalamic disease) - replacement gonadotrophins.
Administer dopamine agonist to combat hyperprolactinaemia.
Name the endogenous sites of production of androgens.
- interstitial Leydig cells of the testes
- adrenal cortex (males and females)
- ovaries
- placenta
- tumours
Name the 4 main actions of testosterone.
- development of the male genital tract
- Maintains fertility in adulthood
- Control of secondary sexual characteristics
- Anabolic effects (muscle, bone)
What proportion of circulating testosterone is protein bound?
98%
Diagram outling action of testosterone - conversion and receptor
Give the clinical uses of testosterone.
- 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.
Define primary amenorrhoea.
Absence of periods. Failure to being spontaneous menstruation by 16 years old.
Define secondary amenorrheoa
Absence of menstruation for 3 months in a woman who previously had cycles
Define oligomenorrhoea.
Irregular long cycles
List the causes of amenorrhoea.
Pregnancy/lactation.
Ovarian failure
- premature ovarian insufficiency
- ovariectomy/chemotherapy.
- overian dysgenesis (Turners 45 XO) - lacking one chromosome.
Gonadotrophin failure.
–Hypo / pit disease
–Kallmann’s syndrome (anosmia, Low GnRH)
–Low BMI
–Post pill amenorrhoea
Hyperprolactinaemia.
Androgen excess (gonadal tumour)
Give some characteristics of Turners syndrome.
short stature
cubitus valgus (wide carrying angle)
gonadal dysgenesis.
How common is Turners syndrome?
1:5000 live female births
How can amenorrhoea be investigated?
Pregnancy test.
LH/FSH, oestradiol (if very low)
Day 21 progesterone (should be high)
Prolactin/thyroid function tests.
Test for androgens (testosterone, androenedione, DHEAS).
Chromosomal analysis (Turners)
Ultrasound scan of ovaries/uterus.
Explain how amenorrhoea might be treated.
Treat cause (e.g. low weight)
HRT in case of primary ovarian failure.
Hypothalamic/pituitary disease - HRT for oestrogen replacement, gonadotrophins (LH/FSH) for fertility.
How common is PCOS?
1 in 12 women of reproductive age.
What is PCOS associated with?
increased cardiovascular risk and insulin resistance.
Outline the criteria for PCOS diagnosis.
Polycystic ovaries on USS
oligo-/anovulation
clinical/biochemical androgen excess.
Name 3 clinical features of PCOS.
Hirsuitism.
menstrual cycle disturbance.
Increased BMI
Name two drugs used to treat PCOS.
Metformin
Clomiphene
Outline the mechanism of action of clomiphene.
Bind to oestrogen receptors in hypothalamus. Block normakl -ve feedback –> increased GnRH and gonadotrophins.
Diagram to show control of prolactin secretion.
Outline the causes of hyperprolactinaemia.
dopamine antagonist drugs.
- anti-emetics (metoclopramide)
- anti-psychotics (phenothiazines)
Prolactinoma
Stalk compression due to pituitary adenoma.
PCOS
Hypothyroidism
Oestrogens (pregnancy, lactation)
Idiopathic
Name the clinical features of hyperprolactinaemia.
Galactorrhoea.
Reduced GnRH secretion/LH action –> hypogonadism.
Prolactinoma
- headaches
- visual field defect.
How can hyperprolactinaemia be treated?
Treat cause - stop drugs being administered that might cause it.
Dopamine agonist
- bromocriptine
- cabergoline
Prolactinoma
- opamine agonist therapy.
- pituitary surgery.
