Endocrine infertility Flashcards
What stimulates release of LH and FSH from the pituitary?
GnRH pulses from the hypothalamus
What does LH stimulate?
Testosterone production in the testes
Which cells does LH specifically stimulate to produce testosterone?
Leydig cells
What is testosterone responsible for?
Secondary sexual characteristics and aids spermatogenesis
Where does FSH stimulate (including cells)?
Sertoli cells in seminiferous tubules -> sperm and inhibin A and B
What does testosterone have a negative feedback effect on?
Hypothalamus and pituitary
What does inhibin have a negative feedback effect on?
Pituitary FSH secretion
What are the three phases of the menstrual cycle?
Follicular phase
Ovulation
Luteal phase
What does LH stimulate in the ovaries?
Production of progesterone and oestradiol
What does FSH develop?
Follicles and inhibin
After day 10, what happens in terms of follicles?
The leading follicle develops into the Graffian follicle
What is the initial effect of oestrogen on LH and FSH?
It inhibits their secretion
In the follicular phase, how does a man and woman’s HPG axis compare?
They are pretty much the same
When does the effect of oestrogen switch from negative feedback to positive feedback?
Once oestrogen levels reach a certain point
This occurs in ovulation– positive feedback
How does oestradiol have a positive feedback effect?
Increases GnRH release
Increases LH sensitivity to GnRH– used to mature eggs
What does the positive feedback effect of oestrogen lead to?
A mid cycle LH surge which triggers ovulation from the leading follicle
What is the definition of infertility?
Inability to conceive after 1 year of regular unprotected sex
How many couples are affected?
1/6
What percentage of infertility is caused by abnormalities in men?
30%
What percentage of infertility is caused by abnormalities in women?
45% (other 25% is unknown)
What happens in primary gonadal failure?
Testes or ovaries are not producing testosterone/oestrogen so there’s no negative feedback on HPG axis meaning you get high GnRH and high LH/FSH
What happens in pituitary disease?
Inability of the pituitary gland to produce FSH and LH so their levels are low and as a result there is low oestradiol and testosterone
GnRH cannot be measured, FSH/LH and testosterone and oestradiol measured
What are the clinical features of male hypogonadism?
Loss of libido Impotence Small testes Decreased muscle bulk Osteoporosis
What are the causes of male hypogonadism?
Hypothalamic/pituitary disease
- Hypopituitarism
- Kallmann syndrome (anosmia and low GnRH)
- Illness/underweight- mainly due to low levels of leptin
What is an example of congenital primary gonadal disease?
Klinefelter’s syndrome XXY
What is an example of acquired primary gonadal disease?
Testicular torsion, chemotherapy
What is the effect of hyperprolactinaemia on the gonads?
Inhibits function
How do you test for male hypogonadism?
Check LH, FSH and testosterone - if they’re all low, MRI the pituitary to check for pituitary problem
Check prolactin
Check sperm count
Chromosomal analysis: Klinefelters
What is azoospermia?
Absence of sperm in ejaculate
What is oligospermia?
Reduced number of sperm in ejaculate
How do you treat male hypogonadism?
Replacement testosterone for all patients-
For fertility: if hypo/pit disease
-s.c gonadotrophins (LH and FSH)
To treat hyperprolactinaemia, you need a dopamine agonist as dopamine is main influence on prolactin release and it has a negative effect
What are the endogenous sites of production of androgens?
Interstitial Leydig cells of 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
How does testosterone exist in the blood?
Heavily bound 98%
What does dihydrotestosterone act on?
- Active form of testoterone
- Androgen receptors
How is dihydrotestosterone formed?
Testosterone is converted by 5 alpha-reductase
What does aromatase convert testosterone to?
17beta-oestradiol
What does 17beta-oestradiol act on?
Oestrogen receptors
In adulthood, what does testosterone increase?
Lean body mass
Muscle mass and strength
Bone formation and mass
Libido and potency
What are the three main gonadal disorders in women?
Amenorrhoea
Polycystic ovarian syndrome (PCOS)
Hyperprolactinaemia
What is amenorrhoea?
Absence of periods
What is primary amenorrhoea?
Failure to develop spontaneous menstruation by the age of 16 years
What is secondary amenorrhoea?
Absence of menstruation in a women for 3 months who has previously had menstrual cycles
What is oligomenorrhoea?
Irregularly LONG cycles
What are the causes of amenorrhoea?
Pregnancy/Lactation Ovarian failure -Premature ovarian sufficiency -Chemotherapy/ovariectomy -Ovarian dysgenesis (Turner's syndrome 45X) Gonadotrophin failure -Hypothalamic/pituitary disease -Kallmann's syndrome -Low BMI -Post-pill amenorrhoea Hyperprolactinaemia Androgen excess: gonadal tumour
What are some features of Turner’s syndrome?
Short stature
Cubitus valgus
Gonadal dysgenesis
What is cubitus valgus?
When the forearm is angled away from the body to a greater degree than normal when fully extended
After how long are you advised to stop the pill and why?
4 years and because if you use the pill for a long time then your periods won’t come back for around 12 months
How would you investigate amenorrhoea?
Pregnancy test
Check LH, FSH and oestradiol
Day 21 progesterone- should be a rise around this time
Prolactin, Thyroid function
Androgens
Chromosomal analysis
Ultrasound scan ovaries/uterus
How do you treat amenorrhoea?
- Treat the cause e.g low weight
- Primary ovarian failure - infertile, HRT
- hypothalamic/pituitary disease- HRT for oestrogen replacement. Fertility: Gonadotrophins (LH and FSH)- part of IVF
What proportion of women of reproductive age are affected by PCOS?
1/12
What is PCOS associated with?
Increased cardiovascular risk and diabetes
What is the criteria to diagnose PCOS?
Need two of the following:
Polycystic ovaries on ultrasound
Oligoovulation/anovulation
Clinical/biochemical androgen excess
What are the clinical features of PCOS?
Hirsutism
Menstrual cycle disturbance
Increased BMI
How is PCOS treated?
- Metformin- Insulin sensitiser used in type II diabetes
- Clomiphene- Anti-oestrogen effect in hypothalamic-pituitary axis. Binds to oestrogen receptors. Results in increased GnRH and gonadotrophins
- Gonadotrophin therapy as part of IVF treatment
What is the main influence on prolactin release?
Dopamine- negative effect
What is the effect of TRH on prolactin release?
Mild stimulatory
What does prolactin stimulate?
Production of milk in lactating women
What does prolactin have a negative feedback effect on?
GnRH pulsatility and LH actions on ovaries and testes
What are the main causes of hyperprolactinaemia?
Dopamine antagonists -anti-emetics (metoclopramides- antisickness) -anti-psychotics (phenothiazines) Prolactinoma Stalk compression due to pituitary adenoma--switches off dopamine PCOS Hypothyroidism Oestrogen (pill), pregnancy, lactation Idiopathic
What are the clinical features of hyperprolactinaemia?
Galactorrhea
Reduced GnRH secretion/LH action leads to hypogonadism
Prolactinoma- headache and visual defects
How do you treat hyperprolactinaemia?
Treat the cause- stop the drugs if that is what is causing it
Dopamine agonists- cabergoline and bromocriptine
Will also cause decrease in size of a prolactinoma
A young woman presents at clinic with:
Secondary amenhorrhea, galactorhea, secondary gonadism
What do you expect her blood results
LOW LH, FSH, Oestradiol
Secondary amenhhorea– LH and FSH could be normal end
Prolactin is inidcated to be high by her galactorhea– prolactinoma
