endocrine infertility Flashcards
(35 cards)
describe the male hypothalamo-pituitary-gonadal axis
- GnRH pulses from the hypothalamus
- stimulates the release of LH and FSH from the pituitary
- LH then stimulates testosterone production in the testes (Leydig cells)
- testosterone is then responsible for the secondary sexual characteristics and aids spermatogenesis
- FSH stimulates Sertoli cells in seminiferous tubules -> sperm and inhibin A and B
- inhibin has a negative feedback on pituitary FSH secretion
what are the three phases in the female menstrual cycle?
follicular phase
ovulation
luteal phase
how long does the female menstrual cycle last?
28 days
what happens in the luteal phase?
If implantation does NOT occur –endometrium is shed (menstruation)
If implantation DOES occur > pregnancy
define infertility
Infertility: inability to conceive after 1 year of regular unprotected sex.
describe the hypothalamo-pituitary-gonadal axis
Female
follicular phase
- LH stimulates production of oestradiol and progesterone in the ovaries
- FSH stimulates follicular development and inhibin
- by around day 10, the leading follicle develops into a graffian follicle
- oestrogen initially negatively inhibits LH and FSH secretion
- so in the follicular phase their HPG axis is basically the same as men
describe the hypothalamo-pituitary-gonadal axis
Female
luteal phase
- once the oestrogen levels reach a certain point it switches from negative to positive feedback
- it increases GnRH release and increases LH sensitivity to GnRH
- this leads to mid-cycle LH surge
- this triggers ovulation from the leading follicle
what is primary gonadal failure?
- this is a defect of the gonads
- the testes or ovaries are not producing testosterone/oestrogen so there is no negative feedback on the HPG axis meaning that you can get high GnRH and High LH and FSH
what is hypothalamic/pituitary disease?
this is caused by an inability of the pituitary gland to produce FSH and LH so their levels are low
as a result you also have low oestradiol/testosterone
Male Hypogonadism - clinical features
Loss of libido = sexual interest / desire Impotence Small testes Decrease muscle bulk osteoporosis
what are the causes behind male hypogonadism?
Hypothalamic-pituitary disease
- Hypopituitarism
- Kallmans syndrome (anosmia & low GnRH)
- Illness/underweight (mainly due to the low levels of leptin)
primary gonadal disease (congenital: klinefelters syndrome, acquired: testicular torsion, chemo)
hyperprolactinaemia
androgen receptor deficiency
what is kallman’s syndrome?
testes originally undescended
stature low-normal
what investigations can you do for male hypogonadism?
LH, FSH, testosterone
If all low»_space; MRI pituitary
Prolactin
Sperm count
Azoospermia = absence of sperm in ejaculate
Oligospermia = reduced numbers of sperm in ejaculate (can also look at sperm under the microscope to check their number and motility)
chromosomal analyss (eg for klinefelters XXY)
what would be the treatment for male hypogonadism?
Replacement testosterone for all patients(thus increases their muscle bulk and protects against osteoporosis)
For fertility: if hypo / pit disease
-subcutaneous gonadotrophins (LH & FSH) injections
Hyperprolactinaemia – dopamine agonist (dopamine has a negative effect on prolactin release)
what are the endogenous sites of production of androgens?
- interstitial Leydig cells of the testes
- adrenal cortex (males and females)
- 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)
what happens to the circulating testosterone?
-98% protein bound
-in different tissues you get testosterone being converted to other things
-5 alpha reductase converts testosterone to dihydrotestosterone (DHT)which then acts on androgen receptors
-aromatase can convert testosterone into 17b-Oestradiol (E2) acts via the oestrogen
receptor (ER)-
e.g. brain and adipose tissue
**DHT and E2 act via the nuclear receptors so they are intracellular and have to go into the nucleus to have an effect
what are the clinical uses of testosterone?
Testosterone in adulthood will increase 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.
what fertility disorders can you get in females?
- Amenorrhoea
- Polycystic Ovarian Syndrome (PCOS)
- Hyperprolactinaemia
what is amenorrhoea?
Amenorrhoea = absence of periods
what are the different types of amenorrhoea?
Primary amenorrhoea = failure to begin spontaneous menstruation by age 16 years
Secondary amenorrhoea = absence of menstruation for 3 months in a woman who has previously had cycles
Oligomenorrhoea = irregular long cycles
what are the potential causes of amenorrhoea?
Pregnancy ! / Lactation
Ovarian failure:
- premature ovarian sufficiency
- Ovariectomy / chemotherapy
- ovarian 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
what are the features of turners syndrome?
short stature
cubitus valgus (wide carrying angle of the forearm)
gonadal dysgenesis
1:5000 live F births
what investigations can you do for amenorrhoea?
Pregnancy test
LH, FSH, oestradiol
Day 21 progesterone (there should be a rise to show that they are ovulating)
Prolactin, thyroid function tests (hyper and hypo can cause problems with periods)
Androgens (testosterone, androstenedione, DHEAS)
Chromosomal analysis (Turners 45 XO)
Ultrasound scan ovaries / uterus
