9. Endocrine infertility Flashcards
what secretes gonadotrophin releasing hormone?
the hypothalamus
what does the secretion of GnRH stimulate?
the release of gonadotrophins (LH&FSH) from the anterior pituitary which (in men) stimulates testosterone release from the testes
what are the 3 phases of menstruation?
- follicular phase
- ovulation
- luteal phase
describe the follicular phase of menstruation
- stimulation of oestradiol release from ovaries (via LH&FSH)
- as oestradiol levels rise, it induces +ve feedback at the hypothalamus
- increase in GnRH and a big LH surge (vital for ovulation)
describe the luteal phase of menstruation
- if implantation does not occur the endometrium is shed (energy consuming)
- menstrual shedding needs to occur otherwise the excessive growth of the endometrium could cause cancer
- if implantation does occur -> pregnancy
what is infertility defined as and what proportion of couples is it a problem for?
inability to conceive after 1yr of regular unprotected sex
1:6 couples
what is primary gonadal failure?
when the ovaries and testes are not working
- if testes aren’t working there is low testosterone -> less -ve feedback -> increased LH/FSH
- if ovaries aren’t working there is less oestradiol -> increased LH/FSH
what is secondary gonadal failure?
when the hypothalamus or pituitary gland isnt working
- problem with the hypothalamus/pituitary -> LH&FSH will be low
- testosterone and oestradiol will be low
what does high FSH&LH but low testosterone/oestradiol suggest?
primary gonadal failure
what does low FSH&LH and low testosterone/oestradiol suggest?
secondary gonadal failure
what are the clinical features of male hypogonadism?
- loss of libido (sexual interest)
- impotence
- small testes
- decreased muscle bulk (testosterone is often used in anabolic steroids)
- osteoporosis (testosterone is involved in bone strength)
what are the 4 main causes of male hypogonadism?
- hypothalamic-pituitary disease
- hypopituitarism
- kallman’s syndrome
- illness/underweight - primary gonadal disease
- congential: klinefelter’s syndrome (XXY)
- acquired: testicular torsion, chemotherapy - hyperprolactinaemia
- androgen receptor deficiency
describe kallman’s syndrome
GnRH neurones don’t migrate and develop properly -> no GnRH released so patient can’t undergo puberty
anosmia (lack of smell)
undescended testes
low-normal stature
what causes anosmia in Kallman’s syndrome?
GnRH neurones and olfactory neurones migrate together in embryogenesis from the base of the brain upwards
how can male hypogonadism be investigated?
- check LH, FSH and testosterone (if all low suggests secondary failure) -> MRI pituitary
- check prolactin (high prolactin switches off gonadal axis)
- check sperm count:
azoospermia - 0 sperm
oligospermia - less sperm - check appearance and motility of sperm
- chromosomal analysis (e.g. for klinefelter’s)
how is male hypogonadism treated?
- replacement testosterone (tablets, injections) to increase muscle bulk and protect against osteoporosis
- subcutaneous gonadotrophin injections to induce spermatogenesis for fertility
- dopamine agonist if the patient suffers from hyperprolactinaemia
what are the endogenous sites of androgen production?
- interstitial leydig cells of the testes
- adrenal cortex
- ovaries
- placenta
- tumours
what are the main actions of testosterone?
- development of the male genital tract
- maintain fertility in adulthood
- control of secondary sexual characteristics
- anabolic effects (muscle, bone)
what are the 2 enzymes involved in the conversion of testosterone and what do they convert testosterone to?
5𝛼-reductase converts testosterone into the active form dihydrotestosterone (DHT) which binds to androgen receptors
aromatase (found in brain and adipose tissue) converts testosterone to 17𝛽-oestradiol which binds to oestrogen receptors
what will testosterone increase in adulthood?
- lean body mass
- muscle size and strength
- bone formation and bone mass
- libido and potency
what are the 3 disorders in the female?
- amenorrhoea
- polycystic ovarian syndrome (PCOS)
- hyperprolactinaemia
what are the different types of amenorrhoea?
primary amenorrhoea - failure to develop spontaneous menstruation by 16yo
secondary amenorrhoea - absence of menstruation for 3 months in a women who previously had cycles
oligomenorrhoea - irregular long cycles
what are the causes of amenorrhoea?
- pregnancy
- lactation (high prolactin stops menstruation)
- ovarian failure: early menopause, ovariectomy, chemotherapy, ovarian dysgenesis (turner’s syndrome)
- gonadotrophin failure: hypothalamic/pituitary disease, kallman’s syndrome, low BMI, post-pill amenorrhoea, hyperprolactinaemia, androgen XS
what are the signs of turner’s syndrome
- short stature
- cubitis valgus (forearm angled away from body)
- gonadal dysgenesis (defective development)
how can amenorrhoea be investigated?
- pregnancy test
- LH, FSH and oestradiol blood measurements
- day 21 progesterone (to show ovulation)
- prolactin measurement
- thyroid function test
- androgens
- chromosomal analysis (e.g. for turner’s syndrome)
- ultrasound scan ovaries/uterus
how is amenorrhoea treated?
- treat the cause (e.g. low weight)
- if primary ovarian failure give HRT to increase fertility and to protect against osteoporosis
- give gonadotrophins (LH&FSH) as part of IVF treatment
what is polycystic ovarian syndrome associated with?
- increased cardiovascular risk
- insulin resistance (diabetes)
what is the criteria to diagnose PCOS?
2 of the following:
- polycystic ovaries on the ultrasound scan
- oligoovulation/anovulation
- clinical/biochemical androgen excess
what are the clinical features of PCOS?
- hirsutism (XS hair growth in a male pattern)
- menstrual cycle disturbance
- increased BMI
how is PCOS treated?
metformin - insulin sensitiser used in type 2 diabetes to prevent onset
clomiphene - anti-oestrogenic effect on the hypothalamo-pituitary axis by binding to oestrogen receptors in the hypothalamus and blocking -ve feedback. this increases GnRH and gonadotrophin secretion to kickstart HPG axis (5 day course)
gonadotrophin therapy as part of IVF treatment - super-stimulating follicles with IVF (however overstimulation can lead to ovarian hyper-stimulation syndrome)
what does excess prolactin do?
switchs off GnRH pulsatility (-> infertility) and stops LH acting on ovaries and testes
what are the causes of hyperprolactinaemia?
- dopamine antagonist drugs
- > anti-sickness tablets
- > anti-psychotics
- prolactinoma
- stalk compression due to pituitary adenoma (mass blocks the secretion of dopamine so prolactin secretion is not inhibited)
- PCOS
- hypothyroidism (primary hypothyroidism increases TRH which stimulates prolactin)
- oestrogens, pregnancy, lactation
- idiopathic
what are the clinical features of hyperprolactinaemia?
- galactorrhoea
- reduced GnRH secretion/LH action -> hypogonadism
- prolactinoma (headaches and visual field defects)
how can hyperprolactinaemia be treated?
- treat the cause: stop drugs
- dopamine agonist (bromocriptine, cabergoline)
- prolactinoma treatment (pituitary surgery)
