Reproductive endocrinology Flashcards
what hormone is produced at implantation
HCG
what does the corpus luteum produce
progesterone
describe how insulin resistance is produced in the pregnant mother
hPL and placental progesterone cause IR to direct nutrition to foetus
if the mother is already insulin resistant then diabetes can occur
when does foetal organogenesis begin
5 weeks, possibly earlier
managing gestational diabetes in mothers?
good sugar control folic acid 5mg consider tablets to insulin regular eye checks avoid ACEI/statin start aspirin 12 weeks
what should be given to a mother with gestational diabetes during labour
IV insulin
IV dextrose
blood sugar control in diabetic mother during pregnancy
pre meal - 4-4.5 mmol/L
2hr post meal - 6-6.5mmol/L
what drug modification should be made in T1DM
insulin increase
what drug modification should be made in T2DM
consider changing metformin to insulin
if on many drugs consider change to insulin pre pregnancy
what drug modification should be made in GDM
metformin, maybe insulin
lifestyle
how many with GDM develop T2DM post pregnancy
50% after 10-15y
true/false - GDM mothers should be monitored 6 weeks post natal either by OGTT or fasting to screen for T2DM
true
preventing diabetes after GDM
keep weight as low as possible healthy diet aerobic exercise annual fasting glucose metformin/pioglitazone?
function of FSH?
males - spermatogenesis
females - growth of ovarian follicles and ovary secretes oestrogen
function of LH?
males - secretion of testosterone
females - ovulation and progesterone production by corpus luteum
describe the release of GnRH
released in a pulsatile manner
constant in males and cyclical in females
high/low frequency pulses drive LH and high/low frequency pulses drive FSH
high frequency - LH
low frequency - FSH
oestrogen/progesterone increases pulsatility frequency of GnRH and oestrogen/progesterone decreases pulsatility frequency of GnRH
oestrogen increases to cause the LH surge
progesterone decreases
describe the purpose of kisspeptin receptors
neurons in hypothalamus don’t have oestrogen/progesterone receptors to respond to changes and so the kisspeptin neurons adjacent to the hypothalamus respond to it §
how long is the female menstrual cycle
roughly 28 days
follicular phase 14±7
luteal is generally 14
describe the relationship of oestrogen to FSH/LH
rising FSH stimulates oestrogen, which exerts -ve feedback to FSH
oestrogen exerts +ve feedback to cause FSH rise and LH surge
how does progesterone influence LH secretion
LH stimulates corpus luteum to produce progesterone, acts by -ve feedback to alter GnRH pulsatility so less LH secreted
follicular growth - what do theca cells do in response to LH
convert cholesterol to androgen
follicular growth - what do granulosa cells do in response to FSH
convert androgen to oestrogen by aromatase
describe folliculogenesis and how one follicle is selected for ovulation
early growth is independent of gonadotrophins
once follicle reaches certain size it becomes gonad dependent and if this doesnt coincide with FSH rise it is lost
describe a possible evolutionary mechanism why follicles are so FSH dependent
rising oestrogen causes initial drop in FSH
only the follicle with most FSH receptors and best vascularity can survive this drop
when does LH surge occur in relation to ovulation
34-36 hours prior
what oestrogen threshold is required for an increase in GnRH pulsatility for the LH surge
200pg/ml
function of progesterone
increased angiogenesis maintains endometrial thickness and increased secretion infertile thick mucus relaxation of myometrium thermogenic inhibits LH
function of oestrogen
increased thickness of endometrium
regulates LH surge
reduced vaginal pH by lactic acid increase
decreased viscosity of cervical mucus
sperms ability to penetrate cervical canal mucus is dependent on
thickness of mucus
motility of sperm
interaction with mucins
interaction with ROS
where is sperm synthesised
seminiferous tubules of testes
describe how testosterone causes sperm production
released into circulation and taken up be sertoli cells
maintains integrity of blood testes barrier
release mature sperm from sertoli cells by influence of peritubular myoid cells
in males what does FSH do and how is it under -ve feedback
acts on sertoli cells for spermatogenesis
-ve feedback by inhibin on hypothalamus/pituitary
in males what does LH do and how is it under -ve feedback
LH acts on leydig cells to primary produce testosterone
also enhances spermatogenesis
free testosterone acts as -ve feedback on hypothalamus and pituitary
what is testosterone broken down to for cell effects and what enzyme breaks it down
broken down to dihydrotestosterone by 5-hydroreductase and oestradiol by aromatase
what is primary hypogonadism in males and how would it appear on bloods
what is affected by primary hypogonadism
decreased testosterone due to less functional testes so less -ve feedback
higher GnRH and FSH/LH
spermatogenesis is usually affected
what is secondary hypogonadism in males, how would it appear on bloods
what is affected by hypogonadism
low testosterone due to hypothalamic/pituitary dysfunction
low testosterone despite low/normal FSH/LH
testosterone and spermatogenesis affected
congenital causes primary hypogonadism
kleinefelter syndrome
cryptorchism
Y chromosome microdeletions
acquired causes primary hypogonadism
testicular trauma/torsion chemotherapy/radiation varicocele orchitis - mumps infiltrative disease - haemachromatosis medications - glucocorticoids, ketoconazole
congenital causes secondary hypogonadism
kallmanns syndrome
prader willi syndrome
acquired causes secondary hypogonadism
pituitary tumour, infection, infiltrative disease, apoplexy, head trauma hyperprolactinaemia obesity, diabetes steroids, opiates acute systemic illness eating disorders excess exercise
what genetic pattern does kleinefelter syndrome have
47XXY or 46XY/47XXY mosaicism
diagnosis of kleinefelter syndrome
karyotyping
increased risks in kleinefelter syndrome?
breast cancer
non-hodgkins lymphoma
what is kallmanns syndrome and what is it associated with
deficiency of GnRH hyposmia or anosmia red-green colour blindness cleft lip/palate unilateral renal agenesis bimanual synkinesis
pre pubertal signs hypogonadism men
small male sexual organs, testes, penis, prostate decreased body hair high pitched voice low libido gynaecomastia decreased bone/muscle mass euchnoidal habitus symptoms as per cause
post pubertal signs hypogonadism men
normal skeletal proportions and penis/prostate/voice
low libido, decreased spontaneous erections
decreased pubic, axillary hair and reduced shaving frequency
reduced testicle volume
gynaecomastia
decreased energy/motivation
decreased muscle/bone mass
symptoms per cause
when is SHBG higher
ageing hyperthyroidism high oestrogen liver disease HIV anti-epileptic drugs
when is SHBG lower
hypothyroidism low oestrogen obesity diabetes steroids nephrotic syndrome
what should be performed if a male with suspected hypogonadism presents with infertility
semen analysis
determining hypogonadism in men?
low AM testosterone x2
if FSH/LH high then primary and karyotype and iron studies
if FSH/LH low/normal then secondary and check medications, prolactin/pituitary hormones, MRI, iron study
testosterone gel - mode of administration and frequency, benefits, disadvantages
transdermal and daily
fast onset and convenient
mimics circadian rhythm
can cause interpersonal transfer, compliance issues and irritation
oral testosterone - mode of administration and frequency, benefits, disadvantages
once daily oral
convenient
nausea
nebido (undecanoate) - mode of administration and frequency, benefits, disadvantages
IM 10-14 weeks
convenient and good compliance, steady level
hard to withdraw side effects, pain at site, cough, contraindicated in bleeding disorders
sustanon (isocaproate) - mode of administration and frequency, benefits, disadvantages
IM 2-3 weeks easy to withdraw, self administered cough following injection local pain at site contraindicated in bleeding disorders
contraindications to testosterone replacement therapy?
hormone responsive cancer
possible prostate cancer, raised PSA or suspicious prostate on DRE
haematocrit >50%
severe sleep apnoea or heart failure
monitoring of TRT
3-6 monthly bloods on start then annual general health/testosterone levels regular PSA, DRE haematocrit signs sleep apnoea
what is amenorrhoea
absent menstruation
what is oligomenorrhoea
cycles >42 days or <8 periods per year
what physiological concept is used in ovulation test kits and how accurate is it
LH surge as ovulation occurs around 36 hours later
97% accurate
what is spinnbarkeit and what does it mean
cervical mucus in high oestrogen becomes thin, slippery and stretchy
signifies presence of ovulation
during and post ovulation, how much does basal body temperature increase by, and when is it measured
0.2-0.4 degrees C
taken in morning before moving around
true/false- if there are regular menstrual cycles then ovulation is highly likely
true
how could you confirm that ovulation is occurring in a regular cycle
midluteal serum progesterone
>30nmol/L x 2
true/false - midluteal progesterone can be done in someone who is anovulatory
false - it can be done, but it is hard in clinical practice to do as the patient has irregular/absent periods
what blood tests would you do in a patient with irregular cycles
hormone evaluation
FSH, LH, oestradiol, testosterone, SHBG, prolactin
in a patient with hypothalamic pituitary failure (type I), how would FSH/LH and oestradiol be
low with oestrogen deficiency
patients with hypothalamic pituitary failure have oligomenorrhoea/amenorrhoea
amenorrhoea
what challenge test can be done in patients with hypothalamic pituitary failure
progesterone challenge test
administration of progesterone to induce period a week later
if +ve then oestrogen levels are not low
if -ve then there is low oestrogen, uterine abnormality or cervical stenosis
causes of hypothalamic pituitary failure
anorexia nervosa excessive exercise stress low BMI brain/pituitary tumours head trauma kallmann's syndrome drugs - steroids/opiates
pre treatment used for all women with suspected/confirmed ovulation disorders?
stabilise weight rubella vaccination semen analysis of partner folic acid check DHx patent fallopian tube modify lifestyle
how would you possibly manage someone with hypothalamic pituitary failure
if hypogonadotrophic hypogonadism
pulsatile GnRH - administered 90mins as IV/s/c pump
gonadotrophin daily injection - risk multiple pregnancy
need to USS monitor responses
what group of ovulation disorders in women are most common
group II - hypothalamic pituitary dysfunction
biochemical features of hypothalamic pituitary dysfunction (group II)
normal gonadotrophins, excess LH
normal oestrogen
diagnosis of PCOS
2/3
signs of hyperandrogenism - acne, hirsutism
oligo/amenorrhoea
polycystic ovaries from USS
treu/false - most patients with PCOS have amenorrhoea
false - they have oligomenorrhoea
how may ovaries appear polycystic on USS
12/more than 2-9mm follicles
increased ovarian volume >10mm
unilateral/bilateral appearance
describe the formation of hyperandrogenism in PCOS
caused due to hyperinsulinaemia which lowers level of SHBG and increases levels of free testosterone
describe the formation of insulin resistance in PCOS
diminished biological response to insulin level
normal pancreatic reserve leads to hyperinsulinaemia
can lead to diabetes in genetically predisposed or in obese
management of PCOS
clomifene citrate metformin may help with clomifene gonadotrophin therapy laparoscopic ovarian diathermy IVF
rule of 4 with laparoscopic ovarian diathermy and possible risk?
ovarian destruction
4 seconds, 40W, 4 punctures
risks associated with ovulation induction?
ovarian hyperstimulation
multiple pregnancy
ovarian cancer theoretically
risks to the mother with multiple pregnancy
postnatal depression pre-eclampsia gestational diabetes hyperemesis anaemia hypertension operative delivery
risks to child with multiple pregnancy
early/late miscarriage
stillbirth
low weight or prematurity
disability - CP, ADHD, speech issues, congenital heart disease
biochemical features of ovarian failure
high FSH/LH
low oestrogen levels
causes of ovarian failure
turner's syndrome fragile X syndrome XX gonadal agenesis autoimmune ovarian faiure bilateral oophrectomy pelvic chemo/radiotherapy idiopathic
management of ovarian failure
HRT
egg/embryo donation
ovary/egg/embryo cryopreservation when ovarian failure anticipated
counselling/support netwoek
biochemical diagnosis hyperprolactinaemia causing amenorrhoea and galactorrhoea
low/normal FSH/LH
low oestrogen
raised prolactin on 2 occasions
normal TFT
management of hyperprolactinaemia
cabergoline first line, stop once pregnancy occurs
