Endocrinology of Infertility Flashcards
Which cells within the testes does LH stimulate and what does it make these cells produce?
Leydig Cells –> they 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) –> they are stimulated to produce sperm and inhibin A and B
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
Once oestrogen reaches a certain level it switches to positive feedback. How does it do this?
It increases the GnRH secretion It increases LH sensitivity to GnRH
Define infertility.
Inability to conceive after 1 year of regular unprotected sex
What is primary gonadal failure and what effects does it have on the HPG axis?
It is a problem with the gonads The testes/ovaries don’t produce enough testosterone/oestrogen so there is no negative feedback on the HPG axis meaning that you get high GnRH, high LH and high FSH.
Describe the levels of the different hormones in the HPG axis in the case of hypothalamic/pituitary disease causing infertility.
Low GnRH
Low FSH
Low LH
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) Illness/underweight Hyperprolactinaemia Androgen receptor deficiency (RARE)
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 (azoospermia – absence of sperm in ejaculate; oligospermia – reduced number of sperm in ejaculate) Chromosomal analysis (check for Klinefelter’s)
What is given to all patients with hypogonadism?
Testosterone to increase muscle bulk and protect against osteoporosis
How do you restore fertility in someone with hypothalamic/pituitary disease?
Subcutaneous gonadotrophin injections – stimulates testosterone release
What is the treatment for hyperprolactinaemia?
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 5-alpha-reductase to dihydrotestosterone (DHT), which acts on androgen receptors Converted by aromatase to 17-beta-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, infrequent cycles
List some causes of amenorrhoea.
Physiological: 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 investigations for amenorrhoea.
Pregnancy test
LH, FSH and Oestradio
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
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
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)
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 (so dopamine can’t get to adenohypophysis) 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
