Endocrine Infertility Flashcards
Which cells within the testes does LH stimulate and what does it make these cells produce?
Leydig Cells Produce testosterone (secondary sexual characteristics + aids spermatogenesis)
Which cells within the testes does FSH stimulate and what does it makes these cells produce?
Sertoli cells (in seminiferous tubules) Produce sperm + inhibin A + B
What does inhibin inhibit?
Pituitary FSH secretion
What are the 3 phases of the menstrual cycle?
Follicular Phase
Ovulation
Luteal Phase
What does LH stimulate in the ovaries?
Oestradiol + progesterone production
What does FSH stimulate in the ovaries?
Follicular development + 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 + 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 GnRH secretion
It increases LH sensitivity to GnRH
Causes mid cycle LH surge leading to ovulation
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?
A problem with the gonads
Testes/ovaries don’t produce enough testosterone/oestrogen so there is no negative feedback on the HPG axis resulting in high GnRH, LH + 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 5 clinical features of male hypogonadism.
Loss of libido Impotence Small testes Decreased muscle bulk Osteoporosis (testosterone has anabolic action in the bone)
State 6 causes of male hypogonadism.
Hypopituitarism Kallmann’s Syndrome (anosmia + low GnRH) Illness/underweight Primary gonadal disease Hyperprolactinaemia Androgen receptor deficiency (RARE)
State 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 + testosterone (if all low- MRI to check pituitary problem)
Prolactin
Sperm count (azoospermia: absence of sperm in ejaculate; oligospermia: reduced number of sperm in ejaculate)
Chromosomal analysis (Klinefelter’s= XXY)
What is given to all patients with hypogonadism?
Testosterone to increase muscle bulk + protect against osteoporosis
How do you restore fertility in someone with hypothalamic/pituitary disease?
Subcutaneous gonadotrophin injections to stimulate testosterone release
What is the treatment for hyperprolactinaemia?
Treat cause- stop drugs
Dopamine agonists – bromocriptine + cabergoline
Pituitary surgery (rarely used because drugs normally works well)
State 5 endogenous sites of production of androgens.
Interstitial leydig cells in the testes Adrenal cortex Ovaries Placenta Tumours
What are 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)
Testosterone is heavily plasma protein bound and it can be converted to other hormones in various tissues. State 2 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?
Increase lean body mass Increase muscle size + strength Bone formation + bone mass Libido + potency (Does NOT restore fertility)
What is the difference between primary and secondary amenorrhoea?
Primary= failure to begin spontaneous menstruation by age 16 Secondary= absence of menstruation for 3 months in a woman who has previously had cycles
What is oligomenorrhoea?
Irregularly long cycles
List 9 causes of amenorrhoea.
Pregnancy Lactation Ovarian failure: Premature ovarian insufficiency, Ovariectomy, Chemotherapy, Ovarian dysgenesis (Turner’s Syndrome (45 X)) Hypothalamic/pituitary disease Kallmann’s syndrome Low BMI Post-pill amenorrhoea (long use of pill, then go off it, it could take a while for the periods to return) Hyperprolactinaemia Androgen excess (gonadal tumour)
State 3 features of Turner’s syndrome.
Short statue
Cubitus valgus (forearm is angled away from the body to a greater degree than normal when fully extended)
Gonadal dysgenesis
State 8 investigations for amenorrhoea.
Pregnancy test
LH, FSH + Oestradiol
Day 21 Progesterone: (high levels indicate ovulation has occurred) measure at day 18, 21 + 24
Prolactin
Thyroid function test (both hyper- + hypothyroidism can cause problems)
Androgens (testosterone, androstenedione, DHEAS)
Chromosomal analysis
Ultrasound scan ovaries/ uterus
What are the implications on health of polycystic ovarian syndrome (PCOS)?
Increased cardiovascular risk Insulin resistance (diabetes)
What are the criteria for diagnosing PCOS?
> 2 of the following:
Polycystic ovaries on ultrasound scan
Clinical/ biochemical signs of androgen excess
Oligoovulation/ anovulation
List 3 clinical features of PCOS
Hirsuitism
Menstrual irregularities
Increased BMI
Describe the treatment for PCOS.
METFORMIN: insulin sensitiser
CLOMIPHENE: anti-oestrogenic effects in the hypo-pit axis – binds to oestrogen receptors in the hypothalamus thereby blocking negative feedback, increases GnRH + 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?
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 + testes
State 9 causes of hyperprolactinaemia.
Dopamine antagonists (anti-emetics + 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 3 clinical features of hyperprolactinaemia?
Galactorrhoea
Reduced GnRH + gonadotrophin secretion: HYPOGONADISM
Prolactinoma: Visual field defect + Headache
Describe treatment of amenorrhoea
Treat cause (e.g. low weight) Primary ovarian failure (Infertile, HRT) Hypothalamic/ pituitary disease (HRT for oestrogen replacement, fertility- gonadotrophins)
