Reproductive endocrinology Flashcards
1
Q
what hormone is produced at implantation
A
HCG
2
Q
what does the corpus luteum produce
A
progesterone
3
Q
describe how insulin resistance is produced in the pregnant mother
A
hPL and placental progesterone cause IR to direct nutrition to foetus
if the mother is already insulin resistant then diabetes can occur
4
Q
when does foetal organogenesis begin
A
5 weeks, possibly earlier
5
Q
managing gestational diabetes in mothers?
A
good sugar control folic acid 5mg consider tablets to insulin regular eye checks avoid ACEI/statin start aspirin 12 weeks
6
Q
what should be given to a mother with gestational diabetes during labour
A
IV insulin
IV dextrose
7
Q
blood sugar control in diabetic mother during pregnancy
A
pre meal - 4-4.5 mmol/L
2hr post meal - 6-6.5mmol/L
8
Q
what drug modification should be made in T1DM
A
insulin increase
9
Q
what drug modification should be made in T2DM
A
consider changing metformin to insulin
if on many drugs consider change to insulin pre pregnancy
10
Q
what drug modification should be made in GDM
A
metformin, maybe insulin
lifestyle
11
Q
how many with GDM develop T2DM post pregnancy
A
50% after 10-15y
12
Q
true/false - GDM mothers should be monitored 6 weeks post natal either by OGTT or fasting to screen for T2DM
A
true
13
Q
preventing diabetes after GDM
A
keep weight as low as possible healthy diet aerobic exercise annual fasting glucose metformin/pioglitazone?
14
Q
function of FSH?
A
males - spermatogenesis
females - growth of ovarian follicles and ovary secretes oestrogen
15
Q
function of LH?
A
males - secretion of testosterone
females - ovulation and progesterone production by corpus luteum
16
Q
describe the release of GnRH
A
released in a pulsatile manner
constant in males and cyclical in females
17
Q
high/low frequency pulses drive LH and high/low frequency pulses drive FSH
A
high frequency - LH
low frequency - FSH
18
Q
oestrogen/progesterone increases pulsatility frequency of GnRH and oestrogen/progesterone decreases pulsatility frequency of GnRH
A
oestrogen increases to cause the LH surge
progesterone decreases
19
Q
describe the purpose of kisspeptin receptors
A
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 §
20
Q
how long is the female menstrual cycle
A
roughly 28 days
follicular phase 14±7
luteal is generally 14
21
Q
describe the relationship of oestrogen to FSH/LH
A
rising FSH stimulates oestrogen, which exerts -ve feedback to FSH
oestrogen exerts +ve feedback to cause FSH rise and LH surge
22
Q
how does progesterone influence LH secretion
A
LH stimulates corpus luteum to produce progesterone, acts by -ve feedback to alter GnRH pulsatility so less LH secreted
23
Q
follicular growth - what do theca cells do in response to LH
A
convert cholesterol to androgen
24
Q
follicular growth - what do granulosa cells do in response to FSH
A
convert androgen to oestrogen by aromatase
25
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
26
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
27
when does LH surge occur in relation to ovulation
34-36 hours prior
28
what oestrogen threshold is required for an increase in GnRH pulsatility for the LH surge
200pg/ml
29
function of progesterone
```
increased angiogenesis
maintains endometrial thickness and increased secretion
infertile thick mucus
relaxation of myometrium
thermogenic
inhibits LH
```
30
function of oestrogen
increased thickness of endometrium
regulates LH surge
reduced vaginal pH by lactic acid increase
decreased viscosity of cervical mucus
31
sperms ability to penetrate cervical canal mucus is dependent on
thickness of mucus
motility of sperm
interaction with mucins
interaction with ROS
32
where is sperm synthesised
seminiferous tubules of testes
33
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
34
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
35
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
36
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
37
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
38
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
39
congenital causes primary hypogonadism
kleinefelter syndrome
cryptorchism
Y chromosome microdeletions
40
acquired causes primary hypogonadism
```
testicular trauma/torsion
chemotherapy/radiation
varicocele
orchitis - mumps
infiltrative disease - haemachromatosis
medications - glucocorticoids, ketoconazole
```
41
congenital causes secondary hypogonadism
kallmanns syndrome
| prader willi syndrome
42
acquired causes secondary hypogonadism
```
pituitary tumour, infection, infiltrative disease, apoplexy, head trauma
hyperprolactinaemia
obesity, diabetes
steroids, opiates
acute systemic illness
eating disorders
excess exercise
```
43
what genetic pattern does kleinefelter syndrome have
47XXY or 46XY/47XXY mosaicism
44
diagnosis of kleinefelter syndrome
karyotyping
45
increased risks in kleinefelter syndrome?
breast cancer
| non-hodgkins lymphoma
46
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
```
47
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
```
48
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
49
when is SHBG higher
```
ageing
hyperthyroidism
high oestrogen
liver disease
HIV
anti-epileptic drugs
```
50
when is SHBG lower
```
hypothyroidism
low oestrogen
obesity
diabetes
steroids
nephrotic syndrome
```
51
what should be performed if a male with suspected hypogonadism presents with infertility
semen analysis
52
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
53
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
54
oral testosterone - mode of administration and frequency, benefits, disadvantages
once daily oral
convenient
nausea
55
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
56
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
```
57
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
58
monitoring of TRT
```
3-6 monthly bloods on start then annual
general health/testosterone levels
regular PSA, DRE
haematocrit
signs sleep apnoea
```
59
what is amenorrhoea
absent menstruation
60
what is oligomenorrhoea
cycles >42 days or <8 periods per year
61
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
62
what is spinnbarkeit and what does it mean
cervical mucus in high oestrogen becomes thin, slippery and stretchy
signifies presence of ovulation
63
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
64
true/false- if there are regular menstrual cycles then ovulation is highly likely
true
65
how could you confirm that ovulation is occurring in a regular cycle
midluteal serum progesterone
| >30nmol/L x 2
66
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
67
what blood tests would you do in a patient with irregular cycles
hormone evaluation
| FSH, LH, oestradiol, testosterone, SHBG, prolactin
68
in a patient with hypothalamic pituitary failure (type I), how would FSH/LH and oestradiol be
low with oestrogen deficiency
69
patients with hypothalamic pituitary failure have oligomenorrhoea/amenorrhoea
amenorrhoea
70
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
71
causes of hypothalamic pituitary failure
```
anorexia nervosa
excessive exercise
stress
low BMI
brain/pituitary tumours
head trauma
kallmann's syndrome
drugs - steroids/opiates
```
72
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
```
73
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
74
what group of ovulation disorders in women are most common
group II - hypothalamic pituitary dysfunction
75
biochemical features of hypothalamic pituitary dysfunction (group II)
normal gonadotrophins, excess LH
| normal oestrogen
76
diagnosis of PCOS
2/3
signs of hyperandrogenism - acne, hirsutism
oligo/amenorrhoea
polycystic ovaries from USS
77
treu/false - most patients with PCOS have amenorrhoea
false - they have oligomenorrhoea
78
how may ovaries appear polycystic on USS
12/more than 2-9mm follicles
increased ovarian volume >10mm
unilateral/bilateral appearance
79
describe the formation of hyperandrogenism in PCOS
caused due to hyperinsulinaemia which lowers level of SHBG and increases levels of free testosterone
80
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
81
management of PCOS
```
clomifene citrate
metformin may help with clomifene
gonadotrophin therapy
laparoscopic ovarian diathermy
IVF
```
82
rule of 4 with laparoscopic ovarian diathermy and possible risk?
ovarian destruction
| 4 seconds, 40W, 4 punctures
83
risks associated with ovulation induction?
ovarian hyperstimulation
multiple pregnancy
ovarian cancer theoretically
84
risks to the mother with multiple pregnancy
```
postnatal depression
pre-eclampsia
gestational diabetes
hyperemesis
anaemia
hypertension
operative delivery
```
85
risks to child with multiple pregnancy
early/late miscarriage
stillbirth
low weight or prematurity
disability - CP, ADHD, speech issues, congenital heart disease
86
biochemical features of ovarian failure
high FSH/LH
| low oestrogen levels
87
causes of ovarian failure
```
turner's syndrome
fragile X syndrome
XX gonadal agenesis
autoimmune ovarian faiure
bilateral oophrectomy
pelvic chemo/radiotherapy
idiopathic
```
88
management of ovarian failure
HRT
egg/embryo donation
ovary/egg/embryo cryopreservation when ovarian failure anticipated
counselling/support netwoek
89
biochemical diagnosis hyperprolactinaemia causing amenorrhoea and galactorrhoea
low/normal FSH/LH
low oestrogen
raised prolactin on 2 occasions
normal TFT
90
management of hyperprolactinaemia
cabergoline first line, stop once pregnancy occurs
